Disease & Vaccine Information

COVID-19 Overview



covid-19

SARS-Coronavirus-2 (SARS-CoV-2) and COVID-19

Most coronaviruses, including those causing the common cold, are not associated with significant mortality. The novel SARS-Coronavirus-2 (SARS-CoV-2) identified in 2019 causes a collection of symptoms that can cause severe illness, which has become known as COVID-19. The SARS-CoV-2 virus is contagious1 and infected persons can be asymptomatic2 or exhibit symptoms ranging from mild to severe. Symptoms include fever; chills; cough; shortness of breath/difficulty breathing; fatigue; muscle, joint or body aches; rash; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting and diarrhea.3  

Complications of SARS-CoV-2 include pneumonia, acute respiratory failure, Acute, Respiratory Distress Syndrome (ARDS), acute kidney, liver, and heart injury, septic shock, disseminated intravascular coagulation (DIC), rhabdomyolysis (muscle breakdown), chronic fatigue syndrome, blood clots and death. Many complications may be caused by a condition known as a cytokine storm.4

Research on natural immunity from SARS-CoV-2 infection varies and suggests that durable immunity to the virus lasts for at least 20 months5 and may be life-long.6 An August 2021 retrospective study of Israel’s second largest HMO, yet to undergo peer review, found that natural immunity “confers longer lasting and stronger protection against infection, symptomatic disease, and hospitalization caused by the Delta variant.”7

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COVID-19 Vaccine

New ways to make vaccines including new technologies and production platforms, such as mRNA vaccines, have  become favored over the older traditional ways to make vaccines in the COVID-19 vaccine race.8 9 Currently, four experimental COVID-19 vaccines and two licensed COVID-19 vaccine10 11 have been granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) for distribution and use in the U.S.12 13 Of the six vaccines in use, four are mRNA vaccines (Comirnaty, Pfizer-BioNTech, Spikevax and Moderna), one utilizes a human adenovirus vector (Janssen) and one is a protein subunit vaccine that uses recombinant nanoparticle technology (Novavax). Over 360 different types of COVID-19 vaccines are being developed worldwide14 and several experimental COVID-19 vaccines may be given EUA status in the near future.15 16

U.S. Emergency Use Authorization does not mean that the FDA has evaluated all safety and efficacy data. Notably, in July 2021 the CDC reported that the fully vaccinated could still become infected and be capable of transmitting the virus to others17 and data from Israel reported vaccine effectiveness for the experimental Pfizer-BioNTech vaccine may be as low as 39 percent.18 While EUA status granted by the FDA facilitates access to vaccines in a public health emergency, this status shields vaccine manufacturers and providers from liability under the Public Readiness and Emergency Preparedness Act (PREP Act).19 Under federal law, EUA vaccine recipients must “have the option to accept or refuse the vaccine” and be informed of its risks.20

NVIC encourages consumers to make informed vaccination decisions and to read the FDA fact sheet and other information and resources provided on our website.

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Quick Facts

SARS-CoV-2 & COVID-19

  • A few coronavirus strains can cause very severe respiratory disease with significant mortality, such as Severe Acute Respiratory Syndrome (SARS) that emerged in China in 2002-200321 and Middle Eastern Respiratory Syndrome (MERS) that was first reported in Saudi Arabia in 2012.22 SARS-CoV-2, which was identified in China in late 201923 and declared a global pandemic by the World Health Organization (WHO) in March 2020,24 25 has a much lower mortality rate than SARS or MERS.26
  • According to the U.S. Centers for Disease Control and Prevention (CDC), in 2020 about 94 percent of COVID-19 related-deaths occurred in persons over age 65 and individuals with underlying poor health conditions.27 Among those the CDC consider to be at highest risk for severe COVID-19 disease are the immunocompromised; pregnant women; individuals with chronic heart, lung or kidney disease; the obese; type 2 diabetics; and individuals with cancer, Down’s syndrome, sickle cell disease and thalassemia. There are other chronic health conditions that might increase risks for severe COVID-19 disease, including asthma, high blood pressure, dementia and neurologic conditions, liver disease, cystic fibrosis, and type 1 diabetes.28

Coronavirus Vaccine

  • On Mar. 10, 2020, the Secretary of Health and Human Services (HHS) invoked the 2005 Public Readiness and Emergency Preparedness (PREP) Act, after declaring that the COVID-19 pandemic was a public health emergency. As a result, manufacturers of COVID-19 vaccines that have been developed to respond to the SARS-CoV-2 pandemic are considered public health emergency “countermeasures”. The PREP Act shields manufacturers and vaccine providers from liability and vaccine injury compensation claims will be processed by the Countermeasures Injury Compensation Program (CICP).29 30 31
  • As of July 22, 2022, there are two COVID-19 vaccines licensed for use in the U.S. Comirnaty,32 an mRNA COVID-19 vaccine developed by BioNTech with Pfizer, is approved for use in persons 12 years of age and older. Spikevax, an mRNA COVID-19 vaccine developed by Moderna, is approved for use in individuals 18 years and older. The FDA has also issued emergency use authorizations (EUA) for four COVID-19 vaccines. Two vaccines utilize mRNA technology (Pfizer-BioNTech and Moderna) and are authorized for use in infants as young as six months. One is a protein subunit vaccine that uses recombinant nanoparticle technology (NOVAVAX) for individuals 12 years and older. One vaccine, manufactured by Janssen is a COVID-19 vaccine that uses a human adenovirus vector (Janssen). While the Janssen vaccine remains authorized for use in persons 18 years and older, it is only available to individuals who are unable to or unwilling to receive another COVID-19 vaccine due to the risk of thrombosis with thrombocytopenia syndrome (TTS) following vaccination.

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IMPORTANT NOTE: NVIC encourages you to become fully informed about COVID-19 and the COVID-19 vaccine by reading all sections in the table of contents to the left, which contains many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

What is SARS-Coronavirus-2 and COVID-19 (SARS-CoV-2)?

 covid-19

Coronaviruses come from a large family of viruses that are known to cause infections like the common cold. Named for their crown-like spiked surfaces, these viruses are further classified into four additional sub-groups known as alpha, beta, delta, and gamma.

First identified in the mid-1960’s, there are seven known coronaviruses that can cause illness in humans. The four common coronaviruses circulating among humans are:1

  • 229E (alpha coronavirus)
  • NL63 (alpha coronavirus)
  • OC43 (beta coronavirus)
  • HKU1 (beta coronavirus)

Symptoms of common coronaviruses include cough, headache, sore throat, runny nose, fever, and general malaise. In persons with heart and lung disease, infants, older adults, and person with immune disorders, additional illnesses may include lower respiratory infections such as bronchitis and pneumonia.2

There are three human coronaviruses known to cause severe illness in humans.

The first coronavirus recognized as causing severe illness in humans was identified in 2003 and became known as Severe Acute Respiratory Syndrome (SARS). Health officials believe that the virus originated from an animal source, possibly a bat, and infected other animals prior to human transmission. The origin of this virus was traced to the Guangdong province of Southern China. Initial symptoms of SARS included headache, malaise, fever, muscle aches, shivering and diarrhea. Shortness of breath, cough, and diarrhea commonly occurred in the first or second week of illness and in serious cases, progressed rapidly to respiratory distress requiring intensive care.3 The outbreak was considered contained by July of 2003, and no cases of the illness have been reported since 2004. SARS was believed to have infected 8,096 individuals and resulted in 774 deaths.4

The second, Middle Eastern Respiratory Syndrome (MERS), was identified by health officials in Saudi Arabia in September 2012. The exact origin of the virus remains unknown; however, it is believed to have originated in bats and spread to camels prior to human transmission. Classic symptoms of MERS include cough, fever, and shortness of breath. Respiratory distress requiring intensive care and mechanical ventilation occurs in severe cases. While the fatality rate of MERS is estimated at 35 percent, health officials believe that the true fatality rate is lower since milder cases are likely not diagnosed. The virus is not easily transmitted, and most infections have occurred in health care settings among personnel providing care to infected individuals. While MERS has been reported in 27 countries, 80 percent of cases have been reported in Saudi Arabia.5 Only two cases of MERS have been reported in the U.S. and both involved health care providers residing and working in Saudi Arabia.6

The third and most recent is the novel SARS-Coronavirus-2 (SARS-CoV-2), which causes a collection of symptoms including severe illness that has become known as COVID-19. Initial reports began on January 8, 2020, when the CDC issued a health advisory alert regarding a cluster of pneumonia cases with links to a wholesale animal and fish market in Wuhan City, in the Hubei province of China. The initial health alert reported illness in 59 individuals with symptom onset dates beginning December 12, 2019 that included shortness of breath and fever. No deaths were reported and according to Chinese health officials, there were no reports of human to human transmission.7

Chinese health officials identified the virus as a novel coronavirus on December 31, 2019, and by the end of January 2020, 217 deaths among 9,776 confirmed cases had been reported. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a “Public Health Emergency of International Concern” with health officials reporting that the origin of the virus was likely an unsanitary food market in Wuhan City, China. WHO officials suggested that infected individuals were exposed after consuming infected bats and snakes from the city’s market.8 One day later, the U.S. Department of Health and Human Services (HHS) Secretary Alex M. Azar II declared the novel coronavirus a U.S. public health emergency.9

COVID-19 Symptoms and Complications

Symptoms of COVID-19, the illness caused by SARS-CoV-2, include:10

  • Cough
  • Congestion
  • Runny nose
  • Shortness of breath
  • Difficulty breathing
  • Fever
  • Chills
  • Fatigue
  • Muscle aches
  • Body aches
  • Sore throat
  • Headache
  • New loss of taste or smell
  • Diarrhea
  • Nausea
  • Vomiting

Complications of the virus include pneumonia, acute respiratory failure, Acute, Respiratory Distress Syndrome (ARDS), acute kidney, liver, and heart injury, septic shock, disseminated intravascular coagulation (DIC), rhabdomyolysis (muscle breakdown), chronic fatigue syndrome, and blood clots.

Many complications may be caused by a condition known as a cytokine storm. This occurs when an infection triggers the immune system to flood the bloodstream with inflammatory proteins referred to as cytokines, which can damage organs and kill tissue.11 Health officials also believe that the virus may trigger a multisystem inflammatory syndrome in children and adolescents known as Multisystem Inflammatory Syndrome in Children (MIS-C). The CDC reports that they do not know what causes this condition but that many children who develop it have a personal health history of exposure to the SARS-CoV-2 virus or have been in contact with an infected individual.12

COVID-19 Broadly Defined to Include all SARS-CoV-2 Infections

According to the CDC’s August 5, 2020 interim case definition for Coronavirus Disease 2019 (COVID-19), a confirmed COVID-19 case is one where laboratory evidence indicates the presence of the SARS-CoV-2 virus by a molecular amplification test13 such as reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) or nucleic acid amplification test (NAAT).14

A probable COVID-19 case is a case where a person meets the clinical criteria for COVID-19 illness based on at least one symptom and the individual is also epidemiologically linked to another confirmed or probable case. The criteria for epidemiological linkage include close contact with a confirmed or probable case of COVID-19 disease or else being considered at risk based on criteria defined by public health officials during an outbreak. Probable cases are also cases confirmed by antigen testing, a rapid test considered less sensitive and not as reliable as molecular amplification tests.15 16

SARS-CoV-2 Variants

Multiple variants of the SARS-CoV-2 virus emerged in the fall of 2020 and continue to circulate worldwide. Like all viruses, SARS-CoV-2 continually evolve because genetic mutations happen during the genome’s replication. A variant is the result of one or more genetic mutations.17

The Centers for Disease Control and Prevention (CDC) classify SARS-CoV-2 variants into four distinct categories: Variant Being Monitored; Variant of Interest; Variant of Concern; and Variant of High Consequence. The variant’s transmissibility, the severity of illness, and the effectiveness of current medical treatments factor into the classification of each variant.

On May 31, 2021, the World Health Organization (WHO) announced the use of “simple, easy-to-say labels for SARS-CoV-2 Variants of Interest and Concern” and reported that letters of the Greek alphabet would be used to identify variants. While scientific names would continue to be used, WHO reported that:18

“While they have their advantages, these scientific names can be difficult to say and recall, and are prone to misreporting. As a result, people often resort to calling variants by the places where they are detected, which is stigmatizing and discriminatory. To avoid this and to simplify public communications, WHO encourages national authorities, media outlets and others to adopt these new labels.”

Monitored variants have included: Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617), Gamma (P.1.), Epsilon (B.1.427 and B.1.429), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Mu (B.1.621, B.1.621.1), Zeta (P.2) and 1.617.3.

The Delta variant, which was designated a Variant of Concern by WHO in May of 2021 due to increased transmissibility. Public health officials noted that both vaccinated and COVID-19 recovered individuals could be susceptible to infection.19 By July 2021, the CDC acknowledged that both vaccinated and unvaccinated infected with the Delta variant were equally contagious.20

In early November 2021, the Omicron variant, which was initially identified in South Africa, was labeled a Variant of Concern by WHO due to the significant number of mutations.21 These mutations were associated with increased transmissibility and reinfection.

As of August 28, 2022, the Omicron variant is the predominant SARS-CoV-2 variant in the U.S. and remains a Variant of Concern.22 23

Public health experts admit that they are uncertain as to how effective the current authorized treatments and vaccines will be against novel SARS-CoV-2 variants.24 25

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Is SARS-CoV-2 Contagious?

covid-19

SARS-CoV-2, which causes COVID-19, is contagious and is transmitted through aerosolized particles and respiratory droplets. These particles and droplets can be inhaled or can enter the mouth, nose, or eyes.1

The theories on the mode of transmission of SARS-CoV-2, however, changed several times throughout the pandemic. Prior to early May 2021, the CDC reported that SARS-CoV-2 was primarily spread person to person through respiratory droplets and was most often transmitted when an infected individual sneezed or coughed near another person. This meant that transmission could occur between individuals spaced more than six feet apart and that the virus could linger in the air even after a person had left the area.2

In early May 2021, the CDC updated information regarding SARS-CoV-2 transmission and acknowledged that airborne transmission of the virus was also a primary mode of transmission.3 This acknowledgement, however, occurred nearly three months after leading experts in industrial health, public health, and medicine had sent a letter to the CDC and White House officials requesting that airborne, or inhalation, transmission of the SARS-CoV-2 virus be promptly addressed.4

The CDC also acknowledges that SARS-CoV-2 transmission can occur when a person touches a contaminated object and then touches their mouth, nose, or eyes.5

There is also evidence that the virus can be spread through the fecal-oral route, which supports the recommendation for frequent handwashing. Infected feces can contaminate food, surfaces, and hands, and has the potential to cause illness.6 In China, health officials have begun using anal swabs to test for SARS-CoV-2 and report their accuracy to be superior to nasal and throat swabs. Anal swabbing was initiated after research noted that traces of the virus can remain longer in the anus than in the respiratory tract.7

A study published November 19, 2020 in The Lancet Microbe found that the SARS-CoV-2 virus was most contagious in the first five days after the onset of symptoms. This study also reported that there was no difference in the viral loads among asymptomatic or symptomatic SARS-CoV-2-positive individuals, and research indicated that people without symptoms clear the virus quicker and therefore less contagious.8 Research studies have also found that viral loads among vaccinated and unvaccinated SARS-CoV-2 positive people to be similar.9 10

A study conducted in the UK found that the SARS-CoV-2 virus lost 90 percent of its virulence within 20 minutes of being exhaled. After only 10 minutes, the virus lost 50 percent of its ability to infect. Humidity of the environment was also determined to play a role in the ability of the virus to infect. When the environment had a humidity level of less than 50 percent, the virus lost its ability to infect within 10 seconds.11 12

SARS-CoV-2 Testing

Importantly, persons who test positive for the SARS-CoV-2 virus may not go on to develop COVID-19 illness. On average, individuals exposed to SARS-CoV-2 will begin to develop COVID-19 symptoms within five days. Most people who develop symptoms will do so within 12 days. Rarely, symptoms may begin within two days or after 14 days.13

Persons that do go on to develop COVID-19 illness may experience mild to moderate symptoms and are generally no longer considered infectious 10 days after the onset of initial symptoms. Persons who develop severe COVID-19 illness are not likely to be infectious after 20 days post-symptom onset; however, persons who are severely immunocompromised may be capable of shedding the virus for longer than 20 days, and longer than 140 days after testing positive for SARS-CoV-2.14

The reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test used to identify individuals infected with the SARS-CoV-2 virus uses a nasal swab to collect RNA from deep within the nasal cavity and is then reverse transcribed into DNA and amplified through cycles. Results from a PCR test are reported as a simple “yes” or “no” answer to the question of whether someone is infected.15

However, the validity of COVID-19 testing has continually been questioned by some health experts. There are reports that the PCR testing for SARS-CoV-2, the virus associated with COVID-19 illness, is too sensitive and adjustments are needed to distinguish people who have insignificant amounts of harmless viral material in their system versus people who are clinically infected with live virus. The most significant concern is that the number of detection cycles for the test is so high that it reports a positive result for people who have infectious live virus as well as a positive result for people who have only a few genetic fragments left over from a past infection and no longer pose a risk to others.16 17

A New York Times review published on August 29, 2020 reported on three sets of testing data that included cycle thresholds (CT) values compiled by officials in Massachusetts, New York and Nevada. The review found that “up to 90 percent of people testing positive barely carried any virus” and experts stated that tests using high CT values may be detecting not only live virus, but also genetic fragments; “leftovers from an infection that pose no particular risk” for contagiousness. The review reported that most tests used a CT value of 40, and noted the CDC’s acknowledgment that samples with a CT value above 33 cycles were unlikely to detect live virus.18

According to the U.S. Food and Drug Administration (FDA), cycle threshold ranges used to determine who is positive are set by commercial manufacturers and laboratories.19

A positive RT-qPCR test does not confirm whether a person is currently ill or will become ill in the future, whether they are infectious or will become infectious, whether they are recovered or recovering from COVID-19, or whether the RT-qPCR test identified a viral fragment from another coronavirus infection in the past. The RT-qPCR test is only capable of reporting that a person has come into contact with coronavirus RNA.20

Carl Heneghan, the director of the Centre for Evidence Based Medicine at the University of Oxford and editor of BMJ Evidence-Based Medicine has expressed concerns regarding the use of PCR testing to confirm a case of COVID-19 and noted:21

“In any other disease we would have a clearly defined specification that would usually involve signs, symptoms, and a test result… We are moving into a biotech world where the norms of clinical reasoning are going out of the window. A PCR test does not equal COVID-19; it should not, but in some definitions it does.”

A systematic review published in December 2020 in Clinical Infectious Diseases focused on COVID-19 viral cultures from PCR samples and assessed their infectious potential. A key finding from this review noted that the data suggests that complete live viruses are necessary for transmission of COVID-19, and not fragments that may be identified by PCR tests utilizing a high CT value. The review also estimated that the recovery of live virus from specimens with a CT value greater than 35 was only 8.3 percent, with five studies in the review reporting no growth in specimens with a CT value ranging from 24 to 35. The review also found that infectious potential declined after day 8, including cases with ongoing high viral loads.22

The CDC also reports that a person who has recovered from COVID-19 may have low levels of virus in their bodies for up to three months after diagnosis and may test positive, even though they are not spreading COVID-19.23

Addressing the controversial CT value aspect of COVID-19 PCR tests, on January 13, 2021, WHO issued a medical product alert and stated that persons who interpret results for specimens tested using PCR methodology should be aware that "careful interpretation of weak positive results is needed."24

A specimen may be considered weak if a high number of cycles are performed prior to virus detection. This may also mean that the person who provided the specimen might not be infectious.25 26 WHO is advising that a positive PCR test that is not consistent with the clinical presentation of COVID-19 should be confirmed through retesting of a new specimen.27

The CDC has revised testing guidelines for SARS-CoV-2 (COVID-19) multiple times. As of August 28, 2022, the CDC is recommending that persons with symptoms of COVID-19 should be tested. Persons who have been in close contact with an infected person are also being advised to test at least five days after exposure. Persons who may have contact with an individual considered at high-risk for COVID-19 are advised to consider testing before contact, specifically if community transmission of the virus is moderate or high. Testing is not advised for asymptomatic individuals who have recovered from COVID-19 in the previous 30 days. If a person tested positive within 31 to 90 days, antigen testing for COVID-19 is recommended. 28

Antigen testing, frequently completed at home, however, is considered less reliable to diagnose COVID-19. Public health officials report that a single negative antigen test result does not necessarily rule out infection and recommend multiple testing (serial testing), repeated at least 48 hours apart.29

Like all testing, SARS-CoV-2 testing is not 100 percent accurate and false-positive and false-negative results can occur. False results are generally attributed to human error in processing, specimen contamination, or to the test’s sensitivity and specificity in accurately detecting the virus.30

Isolation and Quarantine after SARS-CoV-2 Virus Exposure

Since the declaration of the COVID-19 pandemic, the CDC has recommended isolation and quarantine measures to limit the spread of SARS-CoV-2 infections. CDC quarantine guidelines have also been revised several times during the course of the declared pandemic.

As of August 24, 2022, the CDC is recommending that individuals who are exposed to SARS-CoV-2 should take immediate precautions. This includes wearing a good quality mask when around others both at home and in public spaces for at least ten days, and self-monitoring for symptoms of infection. COVID-19 testing is recommended on the sixth day after exposure. If the test result is positive, immediate isolation is advised. Precautions are recommended for at least ten days post-exposure even if a COVID-19 test is negative.31

The CDC is recommending that persons who test positive for COVID-19 isolate for at least 5 days if they are asymptomatic or their symptoms are resolving. Mask use when around others is recommended for another 5 days. The CDC also states that if it is not possible to quarantine for 5 days then a person should wear a well-fitted mask for at least 10 days when around others. If antigen testing is available, infected individuals can opt to test at least 48 hours apart until two sequential tests are negative. Should symptoms of COVID-19 return, individuals are advised to restart isolation.32

COVID-19 positive health care workers (HCW) are advised to quarantine for 10 days, or 7 days with a negative test if they have no symptoms or their symptoms are resolving. In the case of staff shortages, HCW may return to work after five days of quarantine if they are asymptomatic or their symptoms are resolving. If staffing is critical, COVID-19 positive HCW are being advised by the CDC that they can return to work if asymptomatic or mildly symptomatic.33

Immunity after SARS-CoV-2 infection

In January 2021, researchers reported that more than 95 percent of people who recovered from SARS-CoV-2 infection had durable immunity to the virus for at least eight months.34 Another study conducted by researchers at the Washington University School of Medicine in St. Louis found that persons who recover from COVID-19 illness, including those with asymptomatic and mild cases, continued to have lasting immunity upon recovery. Study researchers also speculated that immunity following COVID-19 infection would likely endure long-term.35

A study conducted by the Cleveland Clinic Health System in June 2021 involving 52,238 employees found that "Not one of the 1,359 previously infected subjects who remained unvaccinated had a [Covid-19 infection over the duration of the study” and vaccination did not reduce the risk. Study authors concluded that persons previously infected with SARS-CoV-2 were unlikely to benefit from COVID-19 vaccination.36 Another study specific to health care workers in an urban Massachusetts setting between December of 2020 and September of 2021, when the Delta variant was most prominent, also reported no cases of re-infection with SARS-CoV-2 among those previously infected.37

An August 25, 2021 retrospective study of Israel’s second largest HMO, yet to undergo peer review, compared 673,676 vaccinated individuals who had not been previously infected by SARS-CoV-2, 62,883 unvaccinated individuals and 42,099 previously infected individuals with a single vaccine dose. The study found that natural immunity “confers longer lasting and stronger protection against infection, symptomatic disease, and hospitalization caused by the Delta variant.”38

According to a CDC report published in January 2022 on cases and hospitalizations by COVID-19 vaccination status conducted in New York and California between May 2021 and November 2021, unvaccinated individuals with a history of natural SARS-CoV-2 infection had infection rates of between 14.7 and 29 times lower than unvaccinated individuals without prior infection. In contrast, COVID-19-vaccinated individuals with a past history of SARS-CoV-2 infection were noted to have infection rates that were only between 4.5 and 6.2 times lower. Additionally, hospitalization rates among persons with natural immunity were reported to be between 2 and 6 times lower than those who were vaccinated and had no prior infection.39

Over one hundred studies have reported natural immunity to be equal or better than vaccine acquired immunity.40 41

According to the CDC, as of early October 2021, there have been approximately 146.6 million COVID-19 infections in the U.S.42 A survey of blood donor samples completed in December 2021 and updated in February 2022 found that nearly 95 percent of the U.S. population over age 16 have antibodies to COVID-19, either through infection or vaccination.43 In April 2022, health officials estimated that approximately 75 percent of U.S. infants and children from birth to 11 years had previously been infected.44

The CDC has acknowledged that they have no evidence that any person with natural immunity due to past infection has been able to transmit the virus to another individual.45

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

What is the history of SARS-CoV-2 and COVID-19 in America and other countries?

disease history

On January 8, 2020, the U.S Centers for Disease and Prevention (CDC) issued a health advisory alert regarding a cluster of pneumonia cases with links to a wholesale animal and fish market in Wuhan City, in the Hubei province of China. The initial health alert reported illness in 59 individuals with symptoms that included shortness of breath and fever. No deaths were reported and according to Chinese health officials, there were no reports of human to human transmission. 

Initial reports out of China that the virus was unlikely to spread between humans turned out to be inaccurate as more and more cases were confirmed by Chinese and international health authorities. Early news reports, such as one where a patient was suspected of having infected as many as 14 medical staff in one hospital, showed that the infection was spread more easily than initially thought. 

When the virus was first identified, the CDC stated that little was known about how the novel coronavirus, SARS-CoV-2, spread. Initially, beliefs about virus infectiousness were primarily based on what was known about similar coronaviruses – that most transmission occurs from person-to-person between close contacts (about six feet). 

 

 

Public Health Emergency Declared

Chinese health officials identified the virus as a novel coronavirus on December 31, 2019, and by the end of January 2020, 217 deaths among 9,776 cases had been confirmed. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a “Public Health Emergency of International Concern” with health officials reporting an unsanitary food market in Wuhan City, China as the likely source. WHO officials suggested that infected individuals were exposed through consumption of infected bats and snakes from the city’s market. 

One day later, the U.S. HHS Secretary Alex M. Azar declared the novel coronavirus a U.S. public health emergency.  U.S. citizens who had been in China’s Hubei Province in the previous 14 days would be subject to a 14-day mandatory quarantine prior to entering the U.S. In addition, the U.S. suspended entry for most travelers who were not U.S. citizens and had recently been in China. 

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Quarantine and Isolation

On February 1, 2020, the Secretary of Defense (DOD) Mark Esper approved a request from the U.S. Department of Health and Human Services (HHS) for housing support at military bases for 1,000 people, including American citizens who arrived from other countries and could be subject to mandatory quarantine.  U.S. quarantine stations are located in Washington, D.C, Seattle, San Francisco, San Diego, Philadelphia, Newark, New York, Minneapolis, Miami, Los Angeles, Houston, Honolulu, El Paso, Detroit, Dallas, Chicago, Boston, Atlanta, Anchorage, and San Juan, Puerto Rico. 

The cruise line industry was one of the first to be adversely affected by government quarantine measures. Thousands of passengers and crew members were not permitted to disembark if anyone on the boat tested positive for SARS-CoV-2. In Italy, 6,000 cruise ship passengers were quarantined at the end of January after two guests were suspected of being infected but then tested negative for SARS-CoV-2. Japan ordered a lockdown and quarantine of more than 3,500 passengers and crew on the Diamond Princess cruise ship docked in Yokohama harbor after an 80-year old man from Hong Kong flew to Tokyo and spent a few days on the ship and later tested positive for SARS-CoV-2.  Five days later, 70 passengers on ship had tested positive for SARS-CoV-2, including 14 Americans. Medication was distributed on board to those who needed it and some of the sick passengers were taken to hospitals. 

On February 6, 2020, the New York Times reported that Chinese government authorities responding to the country’s SARS-CoV-2 epidemic ordered round-the-clock house-to-house police searches to take the temperatures of all Wuhan residents and detain anyone who was sick, or suspected of being sick, using force, if necessary, and then “warehousing them in enormous quarantine centers.” A senior Chinese official announced that both the city where the epidemic began and the whole country faced “wartime conditions” and that “There must be no deserters, or they will be nailed to the pillar of historical shame forever.”  

Videos emerged showing people suspected of being infected forcefully being dragged from their homes by officials wearing masks and white protective suits, as the men and women shouted out in protest and unsuccessfully struggled to break free. Another video showed officials wearing masks, dressed in black and carrying large metal sticks chasing a man suspected of being infected through the largely deserted streets of the city as he ran trying to escape being confined in one of the mass quarantine camps.  

New hospitals and makeshift medical treatment centers were erected within weeks. However, officials outside of China questioned whether the shelters were equipped with enough medical supplies and food or adequately staffed to provide basic care to patients. Concerns also included the potential that these crowded facilities could accelerate the spread of not only coronavirus, but also other bacterial and viral diseases.  From the onset of the outbreak, Chinese officials censored all criticism of government officials and Chinese citizen journalists who had broadcasted real-time scenes from the epicenter of the outbreak via their cell phones were detained and arrested by authorities. 

Officials from the Wuhan City Central Hospital also announced that Li Wenliang, the 34-year old ophthalmologist who had been silenced for warning people about the virus in late December 2019, had died from the infection. CNN reported that Dr. Wenliang had been questioned by local authorities in December 2019 after he alerted colleagues and was “later summoned by Wuhan police to sign a reprimand letter in which he was accused of ‘spreading rumors online’ and ‘severely disrupting social order.’”   Chinese officials eventually exonerated Dr. Wenliang and apologized to his family in mid-March 2020.  

On February 11, 2020, the Director-General of WHO, Dr. Tedros Adhanom Ghebreyesus, declared that China’s SARS-CoV-2 outbreak posed a “very grave threat for the rest of the world.” He called for creation of a roadmap to accelerate development of drugs and vaccines “around which research and donors will align.”  By February 11, 2020, there had been 44,138 confirmed cases globally. All but a few hundred cases had occurred in mainland China with a total of 1,107 reported deaths. 

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SARS-CoV-2 Origins Questioned

By mid-February 2020, new questions surfaced about whether the novel coronavirus could be traced back to scientific research conducted in Wuhan labs, a subject that had been widely discussed since January after the outbreak in China emerged.  According to a February 16, 2020 report in the Daily Mail, South China University of Technology scientists wrote a paper questioning whether research on bats and respiratory diseases at the Wuhan Institute of Virology and the Wuhan Centers for Disease Control (WCDC) had created a new chimeric coronavirus capable of infecting humans. The WCDC is located just 300 yards from the fish and wildlife food market thought to be the origin of the coronavirus and is adjacent to the Union Hospital where the first group of doctors were infected. 

On February 15, 2020, a paper was published in The Lancet by Chinese scientists, “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.” In this paper, the authors stated that “In December, 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China, with clinical presentations greatly resembling viral pneumonia” and they described 41 cases hospitalized by January 2, 2020, of which 66 percent (27 people) had been exposed to the food market and 15 percent (6 people) died:

Most of the infected patients were men (30 [73% of 41); less than half had underlying diseases (13 [32%), including diabetes (eight [20%), hypertension (six [15%), and cardiovascular disease (six [15%). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98% of 41 patients), cough (31 [76%), and myalgia or fatigue (18 [44%); less common symptoms were sputum production (11 [28% of 39), headache (three [8% of 38), haemoptysis (two [5% of 39), and diarrhoea (one [3% of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%), RNAaemia (six [15%), acute cardiac injury (five [12%) and secondary infection (four [10%). 13 (32%) patients were admitted to an ICU and six (15%) died.” 

As questions about the origin of the virus began circulating, WHO quickly endorsed the theory that it had spontaneously jumped from animals, most likely bats, to humans in the Wuhan market selling seafood and wildlife animals, additionally, the WHO stated that online speculation to the contrary was “misinformation.” In early February 2020, International Business Times reported that WHO had teamed up with Google to battle online “misinformation” about the SARS-CoV-2 epidemic.  To that end, CNBC reported that the WHO hosted a meeting on February 14, 2020, at Facebook’s Menlo Park, California campus with Google, Amazon, You Tube, Twitter, Verizon and other big tech companies to discuss how to “tamp down on misinformation about the coronavirus.” 

In January 2021, Dr. John Dye, Chief of Viral Immunology for the U.S. Army Medical Research Institute of Infectious Diseases, was interviewed and asked what was known about the origins of SARS-CoV-2 and if the Wuhan lab in China had been ruled out. His response was “No, at this point, nothing has been ruled out. We do not know. It is undetermined whether it was from a laboratory or from an environmental exposure, at this point in time, and we probably never will know.” 

By mid-February 2021, controversy was fueled as revelations by a lead infectious disease expert traveling to Wuhan as a member of an international delegation from the WHO stated that only summary data on early cases were provided to the delegation. Dr. Dwyer added that it was standard practice in an outbreak investigation for raw data to be shared and had yet to be provided by China. 

In an interview on CNN in late March 2021, former CDC Director Robert Redford, MD, stated that it was his opinion that the SARS-CoV-2 virus originated in a laboratory in Wuhan China, and transmission had already begun by September or October of 2019. Redford stated: 

“I do not believe this somehow came from a bat to a human. And at that moment in time, the virus came to the human, became one of the most infectious viruses that we know in humanity for human to human transmission. Normally, when a pathogen goes from a zoonotic to human, it takes a while for it to figure out how to become more and more efficient in human to human transmission.”

Additional investigative reports have provided evidence to supports the lab origin theory and have suggested that the U.S. and China were involved in research involving genetic manipulation of bat coronavirus in an attempt to create vaccines and therapeutics. From information uncovered, evidence has found that these projects were funded by U.S. taxpayers and paid out by National Institutes of Health (NIH), including the National Institute of Allergy and Infectious Diseases (NIAID), and the U.S. Agency for International Development (USAID). Reports have also noted that those who have fought hard to debunk the COVID-19 lab origin theory have ties to the vaccine research and funding partnerships with the Wuhan Institute of Virology (WIV).   

In early May 2021, multiple federal legislators requested that the lab origin theory be fully investigated and have requested information on the U.S funding of research completed at the WIV. 

In September 2021, The Intercept announced that it had received over 900 pages of documents outlining the work of EcoHealth Alliance, an organization based in the U.S. that used money from federal agencies to fund bat coronavirus research at the Wuhan Institute of Virology. The documents were made available to the public for review as part of ongoing Freedom of Information Act (FOIA) legislation. 

The released data revealed that experiments on bat coronaviruses took place at the biosafety Level 3 lab at the Wuhan University Center for Animal Experiment and not the WIV. Grant funding, which totaled $3.1 million, also included nearly $600,000 that was used by the WIV to identify and alter bat coronaviruses that had the capability to infect humans. 

NIAID Director Dr. Anthony Fauci has continually denied that his agency funded bat coronavirus research at the WIV. 

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Risk Factors and Severity

In February 2020, information coming out of China suggested that some people were at high risk of complications from COVID-19 infections, but most people had mild symptoms and recovered without treatment.  WHO stated that: 

“Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirusMost people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness.”

Evidence published in the medical literature by early March 2020 characterizing the type of COVID-19 disease symptoms and risk factors for severe disease among the population in China revealed that common major symptoms (22-88 percent) included fever, cough, myalgia or fatigue, expectoration and difficulty breathing. Minor symptoms (less than 12 percent) included headache or dizziness, diarrhea, nausea and vomiting, with those aged 60 years or older at higher risk.  Another study published by Chinese scientists found that underlying cardiovascular disease, secondary infections, older age and elevated inflammatory indicators in the blood suggested that COVID-19 mortality might be due to “virus-activated ‘cytokine storm syndrome’ or fulminant myocarditis.” 

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Pandemic Declaration

By the end of February 2020, WHO had not yet declared COVID-19 to be a pandemic,  but there had been daily reports in the media warning that COVID-19 was taking a foothold in the U.S.  and many concerned Americans had begun to make preparations to protect themselves by buying masks, hand sanitizer and stocking up on food and household supplies. On March 1, 2020, former U.S. Surgeon General Dr. Jerome Adams sent out a message on Twitter: 

“Seriously people – STOP BUYING MASKS. They are NOT effective in preventing general public from catching coronavirus but if healthcare providers can’t get them to care for sick patients, it puts them and our communities at risk! The best way to protect yourself and your community is with everyday preventive actions, like staying home when you are sick and washing hands with soap and water, to help slow the spread of respiratory illness. Get your flu shot – fewer flu patients = more resources for COVID-19.”

Former CDC Director Dr. Robert Redfield reported to the House Foreign Affairs Committee that, “There is no role for these masks in the community. These masks need to be prioritized for health care professionals that as part of their job are taking care of individuals.” 

WHO declared COVID-19 a global pandemic on March 11, 2020, and urged countries to take strong action to stop its spread     Globally, governments quickly closed borders, restricted or halted travel between and within countries and ordered healthy people to eliminate physical contact with each other by staying in their homes.  The halt to travel and closure of schools, businesses, stores and shopping centers, restaurants, theaters, sports arenas, gyms, beaches, parks and recreation areas, churches, and other places, where children are educated and people conduct business, shop and engage in recreation, sent stock markets into a sudden nosedive   and crippled the world’s economy. 

Two days after WHO declared a COVID-19 pandemic, the New York Times published a widely-quoted article on March 13, 2020, titled “The worst-case estimate for U.S. coronavirus deaths” that raised even more concern about the potential lethality of COVID-19.  The article stated that the CDC had been conferring with epidemiologists at universities around the world and were modeling pandemic COVID-19 scenarios based on what was known about the transmissibility and severity of the new mutated SARS-CoV-2 virus to come up with “worst case” estimates if no actions were taken to slow transmission.

According to the New York Times: 

Between 160 million and 214 million people in the U.S. could be infected over the course of the epidemic, according to one projection. That could last months or even over a year, with infections concentrated in shorter periods, staggered across time in different communities, experts said. As many as 200,000 to 1.7 million people could die. The calculations based on the CDC’s scenarios suggested 2.4 million to 21 million people in the U.S. could require hospitalization, potentially crushing the nation’s medical system, which has only about 925,000 staffed hospital beds. Fewer than a tenth of those are for people who are critically ill.”

An epidemic modeler at Johns Hopkins, Lauren Gardner, was quoted as saying, “There is a lot of room for improvement if we act appropriately,” and urged people to “change their behavior” to alter the course of the pandemic said “changing behavior” would alter the course of the pandemic. A University of Nebraska infectious disease specialist, Dr. James Lawler, was quoted as estimating there would be 96 million Americans infected and 450,000 deaths. 

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CDC Faulty Tests

Testing for the virus, however, was not widely available in many countries. In the U.S., the initial test developed by the CDC was faulty. In most cases, the results came back as inconclusive due to an incorrectly formulated test ingredient. The faulty tests caused significant testing delays. Facilities testing for the virus were forced to send samples directly to the CDC, which resulted in diagnosis delays. Additionally, the CDC severely restricted testing criteria so that few people qualified – including many who presented with COVID-19 symptoms.   

In late February 2020, Science Magazine reported the CDC had only performed 459 tests for the SARS-CoV-2 virus in patients suspected to be infected: 

“The World Health Organization (WHO) has shipped testing kits to 57 countries. China had five commercial tests on the market 1 month ago and can now do up to 1.6 million tests a week; South Korea has tested 65,000 people so far. The U. S. Centers for Disease Control and Prevention (CDC), in contrast, has done only 459 tests since the epidemic began. The rollout of a CDC-designed test kit to state and local labs has become a fiasco because it contained a faulty reagent. Labs around the country eager to test more suspected cases—and test them faster—have been unable to do so. No commercial or state labs have the approval to use their own tests.

In what is already an infamous snafu, CDC initially refused a request to test a patient in Northern California who turned out to be the first probable COVID-19 case without known links to an infected person. The problems have led many to doubt that the official tally of 60 confirmed cases in the United States is accurate.”

Pro-Publica reported: 

“As the highly infectious coronavirus jumped from China to country after country in January and February, the U.S. Centers for Disease Control and Prevention lost valuable weeks that could have been used to track its possible spread in the United States because it insisted upon devising its own test. The federal agency shunned the World Health Organization test guidelines used by other countries and set out to create a more complicated test of its own that could identify a range of similar viruses. But when it was sent to labs across the country in the first week of February, it didn’t work as expected.”

At a congressional hearing on March 12, 2020, Director of the National Institute for Allergy and Infectious Diseases (NIAID) Dr. Anthony Fauci admitted that the U.S. was unable to meet the required capacity for SARS-CoV-2 testing of everyone in the U.S. who needed it. "The system is not really geared to what we need right now," he said. “That is a failing. Let’s admit it.” 

On March 22, 2020, the FDA approved a 45-minute lab test to confirm SARS-CoV-2 infections;  however, the testing delays had significantly impaired the U.S. response to the virus. USA Today reported on March 27, 2020: 

“From its biggest cities to its smallest towns, America’s chance to contain the coronavirus crisis came and went in the seven weeks since U.S. health officials botched the testing rollout and then misled scientists in state laboratories about this critical early failure. Federal regulators failed to recognize the spiraling disaster and were slow to relax the rules that prevented labs and major hospitals from advancing a backup…the nation’s public health pillars — the Centers for Disease Control and Prevention and the Food and Drug Administration — shirked their responsibility to protect Americans in an emergency like this new coronavirus, USA TODAY found in interviews with dozens of scientists, public health experts and community leaders, as well as email communications between laboratories and hospitals across the country. The result was a cascading series of failures now costing lives.”

Former President Donald Trump declared the novel coronavirus outbreak a national emergency on March 13, 2020. The declaration permitted the president to access up to $50 Billion dollars which would be directed to assist states, localities, and territories impacted by the virus.  On March 15, Dr. Fauci said on NBC’s Meet the Press:  

“I think Americans should be prepared that they are going to have to hunker down significantly more than we as a country are doing…I think we should really be overly aggressive and get criticized for overreacting.

Dr. Fauci also reported that he had not received any pushback from government officials to his suggestions and stated that “in fairness, they listen and they generally go with what we say.” 

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Testing Controversy

Results from the reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test are used to identify individuals infected with the SARS-CoV-2 virus and reported as a simple “yes” or “no” answer to the question of whether someone is infected. 

However, the validity of COVID-19 testing has continually been questioned by some health experts. There are reports that the PCR testing for SARS-CoV-2, the virus associated with COVID-19 illness, is too sensitive and adjustments are needed to distinguish people who have insignificant amounts of harmless viral material in their system versus people who are clinically infected with live virus. The most significant concern is that the number of detection cycles for the test is so high that it reports a positive result for people who have infectious live virus as well as a positive result for people who have only a few genetic fragments left over from a past infection and no longer pose a risk to others.   

A New York Times review published on August 29, 2020 reported on three sets of testing data that included cycle thresholds (CT) values compiled by officials in Massachusetts, New York and Nevada. The review found that “up to 90 percent of people testing positive barely carried any virus” and experts stated that tests using high CT values may be detecting not only live virus, but also genetic fragments; “leftovers from an infection that pose no particular risk” for contagiousness. The review reported that most tests used a CT value of 40, and noted the CDC’s acknowledgment that samples with a CT value above 33 cycles were unlikely to detect live virus. 

According to the U.S. Food and Drug Administration (FDA), cycle threshold ranges used to determine who is positive are set by commercial manufacturers and laboratories. 

A positive RT-qPCR test does not confirm whether a person is currently ill or will become ill in the future, whether they are infectious or will become infectious, whether they are recovered or recovering from COVID-19, or whether the RT-qPCR test identified a viral fragment from another coronavirus infection in the past. The RT-qPCR test is only capable of reporting that a person has come into contact with coronavirus RNA. 

Carl Heneghan, the director of the Centre for Evidence Based Medicine at the University of Oxford and editor of BMJ Evidence-Based Medicine has expressed concerns regarding the use of PCR testing to confirm a case of COVID-19 and noted: 

“In any other disease we would have a clearly defined specification that would usually involve signs, symptoms, and a test result… We are moving into a biotech world where the norms of clinical reasoning are going out of the window. A PCR test does not equal COVID-19; it should not, but in some definitions it does.”

A systematic review published in September of 2020 in Infectious Diseases and Therapy stated that lower CT values may be associated with severe COVID-19 outcomes and help in predicting the course of the illness. 

Another review published in December 2020 in Clinical Infectious Diseases focused on COVID-19 viral cultures from PCR samples and assessed their infectious potential. A key finding from this review noted that the data suggests that complete live viruses are necessary for transmission of COVID-19, and not fragments that may be identified by PCR tests utilizing a high CT value. The review also estimated that the recovery of live virus from specimens with a CT value greater than 35 was only 8.3 percent, with five studies in the review reporting no growth in specimens with a CT value ranging from 24 to 35. The review also found that infectious potential declined after day 8, including cases with ongoing high viral loads. 

The CDC reports that a person who has recovered from COVID-19 may have low levels of virus in their bodies for up to three months after diagnosis and may test positive, even though they are not spreading COVID-19. 

Addressing the controversial CT value aspect of COVID-19 PCR tests, on January 13, 2021, WHO issued a medical product alert and stated that persons who interpret results for specimens tested using PCR methodology should be aware that "careful interpretation of weak positive results is needed." 

A specimen may be considered weak if a high number of cycles are performed prior to virus detection. This may also mean that the person who provided the specimen might not be infectious.    WHO is advising that a positive PCR test that is not consistent with the clinical presentation of COVID-19 should be confirmed through retesting of a new specimen. 

In May 2021, the CDC issued new guidance to laboratories and recommended reducing the RT-PCR CT value to 28 when testing persons previously vaccinated with the COVID-19 vaccine. This guidance was issued in response to reporting of breakthrough cases of COVID-19 in fully vaccinated individuals. 

On May 19, 2021, the FDA announced that the use of antibody testing to evaluate immunity to SARS-CoV-2 from past infection or vaccination was not recommended. In this press release, the FDA stated that: 

“Antibody tests can play an important role in identifying individuals who may have been exposed to the SARS-CoV-2 virus and may have developed an adaptive immune response. However, antibody tests should not be used at this time to determine immunity or protection against COVID-19 at any time, and especially after a person has received a COVID-19 vaccination.”

According to the FDA, the available authorized SARS-CoV-2 antibody tests are not validated to evaluate protection or immunity to the virus.  

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Differing Lockdown Approaches

Quarantine measures varied by state; however, most states implemented lockdown measures that significantly restricted Americans. Businesses deemed non-essential were forced to close, causing financial hardships and skyrocketing unemployment claims.      By the end of March 2020, schools in all 50 states had shut down. 

End-of-life care policies for infected individuals became a topic of discussion as hospitals tried to weigh the ethics of resuscitating critically-ill patients against the risk of exposing health care staff to the SARS-CoV-2, especially since most hospitals were ill-equipped to provide their staff with adequate personal protective equipment (PPE). 

These discussions followed reports out of Italy that doctors were only treating patients that were likely to have favorable outcomes. The Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) published guidelines for the criteria that doctors and nurses should follow, comparing “the moral choices Italian doctors may face to the forms of wartime triage and, rather than providing intensive care to all patients who need it, instead apply “distributive justice and the appropriate allocation of limited health resources.” 

The Italian approach was based on utilitarianism, which uses a mathematical model as a guide to public policy that justifies sacrificing the few in order to maximize benefits for a greater number of people. When making intensive care decisions, the doctors would follow criteria that guarantees only patients with “the highest chance of therapeutic success will retain access to intensive care” and the rules would apply to all patients, not only those infected with SARS-CoV-2. They also discussed that “it may become necessary to establish an age limit for access to intensive care” and “Those who are too old to have a high likelihood of recovery, or who have too low a number of ‘life-years’ left even if they should survive, would be left to die.” 

By April 10, 2020, there had been more than 18,000 COVID-19 related deaths reported in the U.S.  According to the CDC, most cases were mild or asymptomatic, including in children,  unless an individual had an underlying chronic health issue such as asthma, obesity, diabetes, autoimmunity, immune suppression, high blood pressure, chronic obstructive pulmonary disease (COPD) or heart disease. 

Large mortality variations among different countries and similar wide variations in mortality among populations living in different states in the U.S. were noted.  At least one study published in early April 2020 found that air pollution subjecting individuals to long-term exposure to fine matter particulates greatly increased the risk for death from COVID-19, and noted that, “The majority of the pre-existing conditions that increase the risk of death for COVID-19 are the same diseases that are affected by long-term exposure to air pollution.” 

Published data from the CDC confirmed that mortality in the U.S. was much higher among senior citizens over age 65, rising to 10 to 27 percent for those over age 85.  The CDC also stated that the risk of hospitalization and death increased with age. Persons over the age of 85  and those with underlying health conditions were noted to be at highest risk of severe illness and death. 

It was also reported that federal health officials were counting all deaths of persons with SARS-CoV-2 as ‘COVID-19’ deaths, regardless of whether they had underlying health issues that may have contributed. 

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Many Elderly Die – Department of Justice Reviews State’s with High Counts

In the U.S., the pandemic hit New York City hard. By April 1, 2020, there were 76,049 cases and 1,941 COVID-19-related deaths.  Temporary hospitals were constructed, and the 1,000 bed U.S. Navy Ship Comfort docked to assist in the pandemic’s response. 

COVID-19 deaths in New York City continued to surge. At the same time, questions about the accuracy of the statistics surfaced. In mid-April, New York City added nearly 3,800 deaths to their COVID-19 death statistics, though these deaths were not confirmed. Health officials justified the addition of these unverified deaths, reporting that over 3,000 excess deaths had occurred in the previous month than what would have been typically expected.   

To free up hospital beds, New York health officials ordered nursing homes to accept COVID-19 positive patients. This decision was criticized by many long-term care advocates who expressed concerns that this would place many frail residents at high-risk of illness. Federal health officials had previously banned nearly all nursing home visits, leaving many residents isolated from loved ones. 

By July 2020, reports indicated that more than 6,300 SARS-CoV-2 positive patients had been discharged into nursing homes to recover, resulting in New York nursing home deaths from COVID-19 being highest in the U.S. Former New York Governor Andrew Cuomo denied any link between his administration’s order to return infected patients to nursing homes and the elevated death rates, and instead placed blame on staff members who continued to work while infected. 

In late August 2020, the U.S. Department of Justice announced that it was reviewing nursing home death rates in New York as well as Pennsylvania, New Jersey, and Michigan, to determine whether laws were broken when these states governors used their emergency powers authority to order nursing homes to accept SARS-CoV-2 positive patients.   

In early February 2021, Melissa DeRosa, a top aide to Former Governor Cuomo privately admitted to Democratic lawmakers that they had withheld the COVID-19 nursing home death toll for fear that federal prosecutors would launch an investigation. Instead of offering an apology to the families of those who died, DeRosa expressed remorse over the political inconvenience that Democratic lawmakers incurred as a result of the Former Governor’s actions.  By mid-February 2021, the media reported on the initiation of an investigation by the FBI and federal prosecutors on Former Governor Cuomo’s nursing home admission policies of March 2020.   

In late July 2021, the U.S. Department of Justice announced that it would not be opening a Civil Rights investigation into COVID-19 nursing home deaths in New York, Michigan, New Jersey, and Pennsylvania. 

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Reopening After Lockdowns in U.S.

Most states that implemented lockdown orders in March began reopening by early May 2020. Reopening plans varied by state, but most continued to restrict crowd size and imposed additional restrictions  including face mask mandates.  A small number of states, however, chose not to issue lockdown orders. These included Nebraska, Iowa, Arkansas, North and South Dakota. In South Dakota, Governor Kristi Noem refused to implement restrictive measures and stated: 

“Ultimately it is the people themselves that are primarily responsible for their safety,” Noem said. “They are the ones who are entrusted expansive freedoms. They are free to exercise their rights to work, worship, and to play or to stay at home and to conduct social distancing.”

Noem was widely criticized, but stood by her decision, stating that it was her duty to uphold the Constitution. 

“The facts on the ground here did not support shelter-in-place,” she said. “We just didn’t have the spread. For me personally, I took an oath to uphold our state Constitution. I took an oath when I was in Congress to uphold the United States Constitution. So, I believe in people’s freedoms and liberties, and I always balance that with every decision that I make as governor. I get overly concerned with leaders who take too much power in a time of crisis because I think that’s how we directly lose our country someday by leaders overstepping their proper role.”

According to a report published by the American Legislative Exchange Council (ALEC) on October 20, 2020, South Dakota was ranked 40th in death rates, with 182.3 deaths per 1 million population. In contrast, New Jersey, which issued strict lockdown orders that included penalties, fines, and even jailtime for violations, was ranked first in death rates, at 1,791.6 per 1 million population. 

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Lockdowns and Reopening Globally

Globally, evidence suggests that lockdowns have not been as effective as hoped and countries that implemented strict restrictions did not fare any better than those who did not. Sweden, a country with a population of 10 million people chose not to lockdown its country because of COVID-19 despite heavy criticism. Although Sweden requested its citizens to stay home if sick and practice social distancing when possible, the government did not close businesses, primary schools, restaurants, shops, gyms and recreational facilities, which has prevented the country from suffering the kind of economic meltdown being experienced by most other countries.  

Without lockdowns, Sweden still reported better mortality rate outcomes than Italy, the U.S and the U.K. and its rank in global COVID-19 death rates continues to decline. As of  October 16, 2021, Sweden was ranked 52nd  among nations in population-adjusted deaths from COVID-19. 

In late March 2021, Reuters reported that infectious disease experts stated Sweden’s overall stance on fighting the pandemic had merits worth studying.” The article noted that the more moderate pandemic measures in use by Sweden had spared the country severe economic impacts in comparison to many European countries, and placed its overall excess mortality at 18 out of 26 countries, with Poland, Spain and Belgium ranking at the top. However, excess death rates should be used with caution and are impacted by overall health of the population, as Sweden’s population is healthier than the EU’s average. 

As of October 16, 2021, U.S public health officials report that international travel to most countries should be avoided. Additionally, most foreign nationals who have been to India, Iran, China, Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, Monaco, San Marino, Vatican City, the U.K, Ireland, South Africa, and Brazil, in the previous 14 days are prohibited from entering the U.S.  

Persons traveling to the U.S. must continue to provide documentation of recovery from COVID-19 or a negative test result within 3 days of travel.  Persons fully vaccinated with FDA Emergency Use Authorization (EUA) COVID-19 vaccines and traveling within the U.S. are not required self-quarantine or to test for COVID-19, unless their destination requires it, and are advised to follow CDC masking and social distancing recommendations. 

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COVID-19 in Children

While older adults and those with pre-existing medical conditions continue to be at a higher risk for severe disease, children remain at minimal risk of developing serious infection. Data has indicated that transmission of SARS-CoV-2 between children and from children to adults occurs infrequently  and in the U.S., children under the age of 14 have accounted for only 0.00035 of one percent of COVID-19 deaths.  Nationwide through October 15, 2021, the CDC reported there were 676 deaths attributed to COVID-19 in children ages 0-17. 

In most states, schools, which closed in response to the pandemic, have reopened. Reopening, however, has varied by state and school districts, and some school districts have opted to provide only virtual schooling options.  For those schools which have reopened, social distancing guidelines, facemask requirements, and additional cleaning protocols have been implemented.   

In February 2021, CDC Director Dr. Rochelle Walensky publicly stated that schools can re-open safely for in-person learning by following guidelines that include social distancing, mask wearing, hand-washing, and contact tracing. Health officials have reported that in-person learning does not increase community infection rates, and transmission of the virus between students rarely occurs. 

In September 2021, a Public Health England report suggested that children who had not received the COVID-19 vaccine had a lower death rate after developing COVID-19 than fully vaccinated adults in all age groups. 

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Cases and Deaths in 2020-2021

As of October 15, 2021, there have been over 44 million cases and over 720,000 COVID-19 related deaths reported to the CDC. This data, however, includes both confirmed and probable cases. 

According to the CDC’s August 5, 2020 interim case definition for Coronavirus Disease 2019 (COVID-19), a confirmed COVID-19 case is one where laboratory evidence indicates the presence of the SARS-CoV-2 virus by a molecular amplification test  such as reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) or nucleic acid amplification test (NAAT). 

A probable COVID-19 case is a case where a person meets the clinical criteria for COVID-19 illness based on at least one symptom and the individual is also epidemiologically linked to another confirmed or probable case. The criteria for epidemiological linkage include close contact with a confirmed or probable case of COVID-19 disease or else being considered at risk based on criteria defined by public health officials during an outbreak. Probable cases are also cases confirmed by antigen testing, a rapid test considered less sensitive and not as reliable as molecular amplification tests.   

COVID-19 death counts also include both confirmed and probable cases. The CDC’s August 5, 2020 interim case definition for Coronavirus Disease 2019 (COVID-19) counts all deaths as a COVID-19 when the death certificate lists COVID-19 disease or SARS-CoV-2 as an underlying cause of death. Probable deaths are those where the death certificate list COVID-19 even without laboratory evidence to confirm the presence of the SARS-CoV-2 virus. 

In early April 2020, Dr. Deborah Birx, the former response coordinator for the White House coronavirus task force, reported that all deaths that occurred in SARS-CoV-2-positive individuals would be counted as a COVID-19 death regardless of whether the virus was responsible. As a result, the CDC’s data does not differentiate between persons who died as a direct result of COVID-19 illness and those who died from other causes but who tested positive for SARS-CoV-2. 

According to data released by the CDC in early September 2020, 94 percent of COVID-19 deaths occurred in persons with significant underlying health conditions. On average, there were 2.6 additional conditions or causes per COVID-related death. The most common respiratory conditions listed included influenza, pneumonia, respiratory failure, and adult respiratory distress syndrome. Comorbid circulatory diseases included hypertension, cardiac arrest, ischemic heart disease, heart failure, and cardiac arrhythmia. Approximately 16 percent of the death certificates listed diabetes, and 11 percent stated that vascular and unspecified dementia contributed or was the cause of death. Three percent had intentional or unintentional injury, poisoning or other type of adverse event listed. 

COVID-19 mortality rates have decreased since the beginning of the pandemic. One study published in October 2020 in the Journal of Hospital Medicine that involved 5,000 patients within New York’s Langone Health System reported an 18 percent mortality rate decrease between March and August 2020. Persons over the age of 75 years had the largest decrease in death rates, from nearly 45 percent in March to just under 10 percent in August. 

A study conducted by the Alan Turing Institute in the United Kingdom reported similar findings over the course of their research period, between March 1 and May 30, 2020. Researchers attribute the decrease in mortality rates to the introduction of effective treatment options and the decline in cases that require critical care interventions. 

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The Great Barrington Declaration

On October 6, 2020, an international coalition of scientists, doctors and medical professionals created and signed a document expressing grave concern regarding the potential negative repercussions of lockdown measures imposed by governments in the wake of COVID-19 and called for a global policy change to what they call “focused protection.” 

The document, entitled The Great Barrington Declaration (GBD), named for the Massachusetts town where organizers gathered and in which the petition was signed, had already secured signatures from 10,233 scientists, 27,860 medical professionals and 504,875 concerned citizens by the end of October. 

The creators of the GBD expressed concerns that “current lockdown policies are producing devastating effects on short and long-term public health,” including fewer healthcare screening visits, worse outcomes for cardiovascular disease and other pre-existing conditions, and serious effects on mental health. Stating that “vulnerability to death from COVID-19 is more than a thousand-fold higher in the old and infirm than the young” and further, that “for children, COVID-19 is less dangerous than many other harms, including influenza,” the authors recommended that measures be put in place to protect vulnerable segments of society, while allowing all others to immediately return to normal life. 

Specifically, they suggested that nursing home staff be limited to those with acquired immunity, staff rotations minimized and staff and visitors frequently tested. Groceries and other essentials should be delivered to elderly who live in the community and the vulnerable should interact with people outside whenever possible. For everyone else, the authors recommended that: 

  • businesses and restaurants should open fully;
  • schools and universities should immediately reopen for in-person attendance, and offer all extracurricular activities;
  • sports, art, music, and other group events should resume; and
  • young low-risk adults should return to work instead of working from home.

In mid-October, the WHO’s Special Envoy, Dr. David Nabarro, stated that lockdowns should not be used as the primary method to control COVID-19 outbreaks. Dr. Nabarro noted that lockdowns will increase poverty and hunger globally and that it is likely that within a year, child malnutrition and poverty will double. Additionally, a study conducted in May 2020 reported that the anxiety and stress of lockdowns will likely “destroy seven times the years of life that lockdowns potentially save.” 

In January 2021, the European Journal of Clinical Investigation published a peer-reviewed paper conducted by Stanford University researchers that reported that their study failed “to find an additional benefit of stay-at-home orders and business closures."  The researchers also reported that

"The data cannot fully exclude the possibility of some benefits. However, even if they exist, these benefits may not match the numerous harms of these aggressive measures. More targeted public health interventions that more effectively reduce transmissions may be important for future epidemic control without the harms of highly restrictive measures." 

In an interview aired on May 20, 2021, former White House COVID-19 advisor, Dr. Scott Atlas, called the COVID-19 associated lockdowns a “heinous abuse of power” and did nothing to protect the most vulnerable populations at risk for the illness. Atlas criticized the response of public health officials, and stated that:

“the lockdowns failed, they still failed to protect the people who are high risk, and the lockdowns destroyed and killed. Many other people destroyed families, sacrificed our children out of fear for adults—even though the children do not have significant risk. And we didn’t care as a country. We kept them out of school.” 

By October 16, 2021, The Great Barrington Declaration had secured signatures from 14,981 medical and public health scientists, 44,167 medical practitioners, and 805,155 from concerned citizens worldwide. 

Back to Topic Links

 

Emergence SARS-CoV-2 Variants

In the fall of 2020, public health officials reported that multiple variants of the SARS-CoV-2 virus had emerged and were circulating worldwide. 

In the United Kingdom, the B.1.1.7 variant (Alpha) emerged in September 2020, and by January 22, 2021 it was confirmed as the dominant circulating strain in England. The transmissibility of this variant was reportedly greater than other circulating SARS-CoV-2 virus variants.   Health officials report that this variant appeared to be 30 to 80 percent more transmissible and increased a person’s risk of death by 30 percent.   

The B.1.351 variant (Beta) was initially detected in Nelson Mandela Bay in South Africa in early October. By December 2020, this variant was found to be the predominant variant circulating in Zambia. Health officials have stated that evidence suggests that the variant is not associated with an increase in disease severity. 

The P.1.(Gamma) variant was first detected in Japan in four travelers from Brazil. In late December, 42 percent of positive samples collected in Manaus, the largest city in the Amazon region of Brazil, were the P.1. variant. Public health officials have expressed concerns that this variant may be transmitted more effectively or be responsible for re-infection. 

On February 11, 2021, the Journal of the American Medical Association (JAMA) published a letter from researchers reporting on a novel SARS-CoV-2 variant, the CAL.20C variant (now B.1.427/B.1.429 or Epsilon), that had emerged in late 2020 in Southern California. By mid-January 2021, this variant was found to account for 35 percent of SARS-CoV-2 specimens from California, and 44 percent of specimens from Southern California. The infectiousness of this strain or its impact on disease severity was reported as unknown.   

Another variant, the B.1.526 (Iota) variant, was identified by research teams from Columbia University and the California Institute of Technology (CalTech). Findings by these teams have been pre-published separately and await peer review.    Both papers indicate that the strain was detected in New York in November 2020 and that this variant may represent an antigenic drift in the virus with possible blunting of current vaccine effectiveness. The Columbia paper indicated that those impacted by this variant “were on average older and more frequently hospitalized”,   while the CalTech paper estimates that the variant accounted for approximately 25 percent of all specimens in February 2021.  In an interview with ABC News published February 25, 2021, the Columbia research team stated they had identified 80 cases of the new variant across New York, New Jersey and Connecticut.

On May 4, 2021, the CDC classified the SARS-CoV-2 variant B.1.617 (Delta) and it’s three sub lineages, B.1.617.1, B.1.617.2, and B.1.617.3, as variants of interest.  These variants, which originated in India, were declared variants of concern by the World Health Organization (WHO) on May 10, 2021. According to the WHO, these variants are associated with increased transmissibility and decreased neutralization. As a result, vaccinated individuals and persons who have previously recovered from a COVID-19 infection may be at risk for infection from this variant.  A technical briefing published by Public Health England on June 11, 2021 noted that almost one third of individuals who died with the Delta variant were fully vaccinated.  In the June 18, 2021 Public Health England Technical report, the death rate in fully vaccinated individuals was 6.6 times higher than among unvaccinated people. 

By the end of June 2021, almost 90 percent of COVID-19 cases in Israel were reported as being from the Delta variant, with 50 percent occurring in fully vaccinated adults.  Health experts report the Delta variant to be more easily transmissible and have also acknowledged that vaccinated individuals are capable of spreading the virus on to others, as COVID-19 vaccines are unable to stop viral transmission. 

As of October 15, 2021, the CDC has reported the Delta variant to be the predominant strain in the U.S., and more than twice as contagious as previous variants.  The Delta variant has been labeled a Variant of Concern and the CDC is continuing to monitor the spread of this variant.   

The C.37 variant (Lambda), first identified in Peru in August 2020, was classified by WHO as a Variant of Interest on June 14, 2021.  A pre-print study posted on bioRxiv ahead of peer review in late July 2021 reported the Lambda variant to be highly contagious and more resistant to vaccines. 

On August 30, 2021, WHO designated the Mu variant a Variant of Interest.  Initially identified in Columbia in January 2021, this variant, also known as B.1.621, has become increasingly prevalent in South America. WHO reports that "the Mu variant has a constellation of mutations that indicate potential properties of immune escape," but state that further studies are needed on the variant. As of September 2, 2021, nearly all US states had reported the Mu variant. 

Health experts admit that they are uncertain as to how effective the current authorized treatments and vaccines will be against these novel variants.   

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Updated October 20, 2021

 

Can COVID-19 Cause Injury and Death?

disease injury death

COVID-19 Cases and Deaths

As of August 28, 2022, there have been over 93 million cases and over one million COVID-19 related deaths reported to the CDC. This data, however, includes both confirmed and probable cases.1

According to the CDC’s August 5, 2020 interim case definition for Coronavirus Disease 2019 (COVID-19), a confirmed COVID-19 case is one where laboratory evidence indicates the presence of the SARS-CoV-2 virus by a molecular amplification test2 such as reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) or nucleic acid amplification test (NAAT).3

A probable COVID-19 case is a case where a person meets the clinical criteria for COVID-19 illness based on at least one symptom and the individual is also epidemiologically linked to another confirmed or probable case. The criteria for epidemiological linkage include close contact with a confirmed or probable case of COVID-19 disease or being considered at risk based on criteria defined by public health officials during an outbreak. Probable cases are also cases confirmed by antigen testing, a rapid test considered less sensitive and not as reliable as molecular amplification tests. 4 5

The CDC’s August 5, 2020 interim case definition for Coronavirus Disease 2019 (COVID-19) counts all deaths as a COVID-19 when the death certificate lists COVID-19 disease or SARS-CoV-2 as an underlying cause of death. Probable deaths are those where the death certificate list COVID-19 even without laboratory evidence to confirm of the presence of the SARS-CoV-2 virus.6

According to data released by the CDC in early September 2020, 94 percent of COVID-19 deaths occurred in persons with significant underlying health conditions. On average, there were 2.6 additional conditions or causes per COVID-related death. The most common respiratory conditions listed included influenza, pneumonia, respiratory failure, and adult respiratory distress syndrome. Comorbid circulatory diseases included hypertension, cardiac arrest, ischemic heart disease, heart failure, and cardiac arrhythmia. Approximately 16 percent of the death certificates listed diabetes, and 11 percent stated that vascular and unspecified dementia contributed or was the cause of death. Three percent had intentional or unintentional injury, poisoning or other type of adverse event listed.7

COVID-19 mortality rates have decreased since the beginning of the pandemic. One study published in October 2020 in the Journal of Hospital Medicine that involved 5,000 patients within New York’s Langone Health System reported an 18 percent mortality rate decrease between March and August 2020. Persons over the age of 75 years had the largest decrease in death rates, from nearly 45 percent in March to just under 10 percent in August.8

A study conducted by the Alan Turing Institute in the United Kingdom reported similar findings over the course of their research period, between March 1 and May 30, 2020. Researchers attribute the decrease in mortality rates to the introduction of effective treatment options and the decline in cases that require critical care interventions.9

COVID-19 Complications and Injuries

Most people who become infected with SARS-CoV-2 will have mild symptoms and recover fully without requiring medical treatment.10 However, COVID-19 can have serious complications that lead to adverse health outcomes.

Complications of COVID-19 disease include pneumonia; acute respiratory distress syndrome (ARDS); acute kidney, liver, and heart failure or damage; septic shock; disseminated intravascular coagulation (DIC); rhabdomyolysis (muscle breakdown); chronic fatigue syndrome; blood clots and death.11 Many complications may be caused by a condition known as a cytokine storm. This occurs when an infection triggers the immune system to flood the bloodstream with inflammatory proteins referred to as cytokines, which can damage organs and kill tissue.12

Health officials report that they are continuing to investigate a rare, serious multisystem inflammatory condition which they report to be related to COVID-19. Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition where various organs of the body become inflamed. Inflammation can occur in the heart, lungs, kidneys, skin, brain, gastrointestinal system, or eyes. Symptoms of the syndrome can include neck pain, rash, diarrhea, vomiting, red eyes, excessive fatigue, and abdominal pain. The CDC reports that they do not know what causes this condition but that many children who develop it have a personal health history of exposure to the SARS-CoV-2 virus or have been in contact with an infected individual.13

Adults may also be at risk for developing a similar condition to MIS-C, known as Multisystem Inflammatory Syndrome in Adults (MIS-A), days to weeks following SARS-CoV-2 infection. Symptoms are similar to those found in children, but may also include low blood pressure and chest pain. The CDC states that they still do not know what triggers this conditions and report that they are continuing to research the syndrome.14

According to public health officials, individuals who recover from COVID-19 may have symptoms that persist for weeks to months after the acute illness resolves. Referred to as COVID-19 “long haulers”, recovered individuals may experience debilitating symptoms which include shortness of breath, nausea, diarrhea, racing heart, intermittent high fever, as well as neurological problems such as memory loss, “brain fog”, and attention problems.15 16

One large study conducted by King’s College London found that approximately 10 percent of persons who had recovered from COVID-19 reported persistent symptoms at one month. Between 1.5 and 2.5 percent of recovered individuals reported ongoing health problems three months post-infection. This study also found that the median age for those with persistent symptoms was 45 years and that women were more likely than men to suffer long-term.17

The CDC, however, acknowledges that there are no tests to confirm a diagnosis of long COVID and report that some people with symptoms of long COVID have had no prior history of a COVID-19 infection or positive COVID-19 test.18

COVID-19 Death Controversies – Dying With and Dying From COVID-19

In early April 2020, Dr. Deborah Birx, the former response coordinator for the White House coronavirus task force, reported that all deaths that occurred in SARS-CoV-2-positive individuals would be counted as a COVID-19 death regardless of whether the virus was responsible. As a result, the CDC’s data does not differentiate between persons who died as a direct result of COVID-19 illness and those who died from other causes but who tested positive for SARS-CoV-2.19

The CDC’s August 5, 2020 interim case definition for Coronavirus Disease 2019 (COVID-19) counts all deaths as a COVID-19 when the death certificate lists COVID-19 disease or SARS-CoV-2 as an underlying cause of death. Probable deaths are those where the death certificate list COVID-19 despite no laboratory evidence to confirm of the presence of the SARS-CoV-2 virus.20

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Who is at Highest Risk for Getting SARS-CoV-2 and COVID-19 Ilness?

covid-19

Persons considered most at risk for developing complications from COVID-19 include those with cardiovascular disease, hypertension, cerebrovascular disorders, cystic fibrosis, pulmonary fibrosis, liver disease, Downs Syndrome, dementia and neurological disorders, chronic obstructive pulmonary disease (COPD), type 1 and type 2 diabetes mellitus, chronic kidney disease, cancer, sickle cell disease, thalassemia, and those who are immunocompromised due to solid organ transplant, HIV, immune deficiencies, blood or bone marrow transplant, or those taking medications that suppress the immune system.1

Persons who are obese (body mass index of 30 or higher), pregnant, smokers, including current and former smokers, and persons with substance use disorders are also considered to be at a higher risk of developing severe illness.2

The CDC states that the risk of hospitalization and death increases with age, and that individuals over the age of 85 are at the greatest risk of developing severe illness.3

In the U.S., African Americans have been disproportionally affected by SARS-CoV-2, with higher rates of COVID-19 illness and death reported in comparison to white Americans. However, African Americans have higher rates of underlying chronic illness including diabetes, hypertension, and heart disease, which are known to increase a person’s risk of developing complications from SARS-CoV-2. Many African Americans are also critical front-line workers with jobs considered vital to the community, which may also increase rates of infection within the African American population.4 5

Limited access to health care, lack of health insurance, and distrust of medical personnel are additional factors which contribute to higher rates of severe illness among African Americans. Research has also found that hidden biases exist in health care that prioritizes white Americans over African Americans.6

Additionally, persons of Asian, Hispanic, and Native American descent have also been disproportionally impacted by COVID-19 disease and have experienced higher rates of hospitalizations and deaths in comparison to white Americans. However, the higher rates among racial and ethnic minorities in the U.S. has been attributed to lower socioeconomic status among these populations, rather than a predisposition to the illness. Many Blacks, Hispanics, and persons of Native American descent are more likely to reside in crowded conditions, in multigenerational households, be employed in positions that can’t be performed remotely, and use public transportation. As a result, they are more likely to be exposed to the SARS-CoV-2 virus.7

Ethnic and racial minorities are known to have less access to health care services and often less likely to have adequate health insurance. As a result, they may not seek prompt treatment for symptoms, which places them at higher risk of hospitalization and death if initial care begins at a later point in the disease process.8

According to the National Academies of Sciences, Engineering, and Medicine:9

“People of color — specifically Black, Hispanic or Latinx, and American Indian and Alaska Native — have been disproportionately impacted by COVID-19 with higher rates of transmission, morbidity, and mortality. Currently there is little evidence that this is biologically mediated, but rather reflects the impact of systemic racism leading to higher rates of co-morbidities that increase the severity of COVID-19 infection and the socioeconomic factors that increase likelihood of acquiring the infection, such as having front line jobs, crowded living conditions, lack of access to personal protective equipment, and inability to work from home.”

Individuals who are not proficient in English, particularly those who lack an understanding of health literacy, have also been noted to have poorer outcomes. Experts report that information provided by public health officials is not adequately communicated and distributed to these populations, placing them at higher risk of severe outcomes.10


IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Who is at Highest Risk for Complications from SARS-CoV-2 and COVID-19?

covid-19

Persons considered most at risk for developing complications from COVID-19 include those with cardiovascular disease, hypertension, cerebrovascular disorders, cystic fibrosis, pulmonary fibrosis, liver disease, Downs Syndrome, dementia and neurological disorders, chronic obstructive pulmonary disease (COPD), type 1 and type 2 diabetes mellitus, chronic kidney disease, cancer, sickle cell disease, thalassemia, and those who are immunocompromised due to solid organ transplant, HIV, immune deficiencies, blood or bone marrow transplant, or those taking medications that suppress the immune system1

Persons who are obese (body mass index of 30 or higher), pregnant, smokers, including current and former smokers, and persons with substance use disorders are also considered to be at a higher risk of developing severe illness2

The CDC states that the risk of hospitalization and death increases with age, and that individuals over the age of 85 are at the greatest risk of developing severe illness.3

In the U.S., African Americans have been disproportionally affected by SARS-CoV-2, with higher rates of COVID-19 illness and death reported in comparison to white Americans. However, African Americans have higher rates of underlying chronic illness including diabetes, hypertension, and heart disease, which are known to increase a person’s risk of developing complications from SARS-CoV-2. Many African Americans are also critical front-line workers with jobs considered vital to the community, which may also increase rates of infection within the African American population.4 5

Limited access to health care, lack of health insurance, and distrust of medical personnel are additional factors which contribute to higher rates of severe illness among African Americans. Research has also found that hidden biases exist in health care that prioritizes white Americans over African Americans.6

Additionally, persons of Asian, Hispanic, and Native American descent have also been disproportionally impacted by COVID-19 disease and have experienced higher rates of hospitalizations and deaths in comparison to white Americans. However, the higher rates among racial and ethnic minorities in the U.S. has been attributed to lower socioeconomic status among these populations, rather than a predisposition to the illness. Many Blacks, Hispanics, and persons of Native American descent are more likely to reside in crowded conditions, in multigenerational households, be employed in positions that can’t be performed remotely, and use public transportation. As a result, they are more likely to be exposed to the SARS-CoV-2 virus.7

Ethnic and racial minorities are also known to have less access to health care services and often less likely to have adequate health insurance. As a result, they may not seek prompt treatment for symptoms, which places them at higher risk of hospitalization and death if initial care begins at a later point in the disease process.8

According to the National Academies of Sciences, Engineering, and Medicine:9

“People of color — specifically Black, Hispanic or Latinx, and American Indian and Alaska Native — have been disproportionately impacted by COVID-19 with higher rates of transmission, morbidity, and mortality. Currently there is little evidence that this is biologically mediated, but rather reflects the impact of systemic racism leading to higher rates of co-morbidities that increase the severity of COVID-19 infection and the socioeconomic factors that increase likelihood of acquiring the infection, such as having front line jobs, crowded living conditions, lack of access to personal protective equipment, and inability to work from home.”

Individuals who are not proficient in English, particularly those who lack an understanding of health literacy, have also been noted to have poorer outcomes. Experts report that information provided by public health officials is not adequately communicated and distributed to these populations, placing them at higher risk of severe outcomes.10


IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Updated October 20, 2021

 

SARS-CoV-2 and COVID-19 Prevention and Treatment Options

covid-19

Prevention

Avoiding exposure to the SARS-CoV-2 is the best way to prevent illness. Staying away from individuals who are ill or who may have been exposed to the virus can reduce your risk of contracting the virus.1

Washing hands with soap and water or using an alcohol-based hand sanitizer when handwashing facilities are not available can also be effective in reducing infection risk.2

Mask Mandates and Evidence

In 2020, the CDC recommended the use of facemasks to prevent the spread of SARS-CoV-2,3 and many states and jurisdictions invoked mask mandates in indoor settings and public spaces, including schools.4 The CDC also imposed a mask mandate when traveling on buses, trains, airplanes, and other forms of public transportation, which was eventually struck down in April 2022. 5

In the spring of 2020, the National Academies of Sciences, Engineering, and Medicine conducted a rapid review of the available literature on the use of fabric face coverings and concluded that:

“There is little evidence regarding the transmission of small aerosolized particulates of the size potentially exhaled by asymptomatic or presymptomatic individuals with COVID-19. The extent of any protection will depend on how the masks are made and used. It will also depend on how mask use affects users’ other precautionary behaviors, including their use of better masks, when those become widely available. Those behavioral effects may undermine or enhance homemade fabric masks’ overall effect on public health. The current level of benefit, if any, is not possible to assess.” 6

Harms associated with the use of fabric masks include the reduction of tissue and blood oxygenation and the increase in carbon dioxide levels. Detoxification is also hindered by the reduction of oxygenation which can impair the immune system and cause additional psychological and physical issues. The use of cloth masks has also been found to increase the risk of infection and the spread of viral illnesses.7

A working paper published by the Cato Institute in November 2021 reviewed the observational, mechanistic and clinical evidence related to the use of cloth masks in the community setting to reduce the spread of respiratory infections and concluded that the data was inadequate to determine clear benefit (or harm).8

In early August 2021, CIDRAP Director, Dr. Michael Osterholm, who has also served as an adviser on President Joe Biden's COVID-19 transitional advisory board, admitted that cloth masks do little to stop SARS-CoV-2 transmission. Despite publicly acknowledging that masks were not effective, Osterholm stated that he supported their use in public spaces.9

In February 2021, the CDC recommended the use of two masks to prevent the spread of SARS-CoV-2 virus.10 This recommendation was based on laboratory simulations studies conducted by the CDC, which reported that wearing a surgical mask underneath a cloth mask improved the fit and filtration. Limitations to the study included the use of only one type of cloth and procedure mask, the lack of different combinations of masks (two cloth masks, surgical mask over a cloth mask) and the inability to generalize among differing populations such as children. Additionally, study authors noted that while the use of two masks might inhibit viral transmission, it also had the potential to cause visual and breathing impairments.11

On April 2, 2021, the CDC issued new mask guidance stating that the fully vaccinated could gather with other fully vaccinated persons indoors, or with the unvaccinated from one other household, unless they lived with someone who was at an increased risk for severe COVID-19. The fully vaccinated also did not need to stay away from others or get tested for COVID-19 after exposure to someone with COVID-19, unless they became symptomatic.12

The CDC updated guidance again on April 27, 2021 and continued to recommend that in indoor spaces, fully vaccinated individuals should continue to mask, wash hands frequently, cover sneezes and coughs, and follow any business or school guidelines. However, fully vaccinated persons could gather with other fully vaccinated people indoors without masks, or with unvaccinated people of any age, except when visiting someone with an increased risk for severe COVID-19, or who lives with someone at increased risk. Fully vaccinated individuals could also go outdoors without masks, except when gathering in large crowds, but they were still advised to avoid large indoor gatherings, to take precautions to protect themselves while traveling, to be vigilant about symptoms, and to get tested when they occur.13

In May 2021, the CDC announced that fully vaccinated individuals could resume activities without masking or physically distancing, except where required by law, workplace, or local requirements. Additionally, they could travel domestically without testing or self-quarantine, and travel internationally without testing unless their destination required it, and would not be required to self-quarantine on return. Vaccinated persons exposed to someone with SARS-CoV-2 were also advised that they would not need to self-quarantine or test unless symptomatic.14

After acknowledging that fully vaccinated persons could still become infected with SARS-CoV-2 and transmit the virus on to others, the CDC issued a health alert on July 27, 2021 and advised fully vaccinated people to wear a mask in indoor public settings in areas of high or substantial viral transmission.15

In addition to questions regarding the effectiveness of masks, the safety of their use, especially among children, has been called into question.

In June 2021, a University of Florida laboratory analyzed six masks, five that were worn by children between 6 and 11 years of age, and one worn by an adult, and found the presence of 11 dangerous pathogens. These included bacteria that cause meningitis, diphtheria, pneumonia, as well as parasites and fungi. Of the masks analyzed, one was polyester, two were cotton, and three were surgical.16

Another June 2021 study published in the Journal of the American Medical Association's Pediatrics, found that children who wore masks were exposed to dangerous levels of carbon dioxide. 17  This study, however, was retracted by the journal on July 16, 2021. The study’s lead author, Harald Walach, has publicly stated that “the retraction was political, because some people did not like our data.”18

A retrospective study conducted by researchers in Germany which included over 20,000 children and noted the experiences of nearly 26,000 children found that masking children caused both physical and psychological harms. These harms included fatigue or drowsiness, headaches, concentration impairments, irritability, malaise, impairments in learning, depressed moods, and a reluctance to attend school.19

The CDC continues to promote the use of masks as a method to reduce the risk of viral transmission, and report that consistently wearing a well-fitted mask is better than not wearing one.20 Multiple studies, however, have found that masks show little or no benefit, and may potentially cause harm. 21 22 23 24 25

Vitamin D and Severe COVID-19 Illness

Individuals who are deficient in vitamin D have been found to be at an increased risk of severe COVID-19 disease.26 27 In addition to strengthening teeth and bones, vitamin D supports nervous, brain and immune system health, lung and cardiovascular function and regulates insulin levels. Ensuring adequate vitamin D levels may prevent a person from developing serious COVID-19 illness.28 29 30 31

A large-scale observational study by the University of Chicago that was published in JAMA Open Network in March 2021 revealed that high vitamin D levels may be protective against COVID-19. The primary investigator noted that while the recommended dietary allowance for vitamin D is 600 to 800 international units (IUs) per day, the National Academy of Medicine states that up to 4,000 IUs per day is safe for the majority of people.32

Another study published in Scientific Reports in September 2021 found that persons with low vitamin D levels were at higher risk of serious disease, increased intensive care unit stays, and death.33

Additional Nutritional Information 

A review published British Medical Journal Nutrition, Prevention & Health in May 202034 stated that while there were no published nutrition studies specific to COVID-19 and SARS-CoV-2:

“Severe infection of the respiratory epithelium can lead to ARDS, characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by the n-3 fatty acids EPA and DHA, possibly through their metabolism to SPMs. This therapeutic approach has not been attempted in severe COVID-19 and warrants investigation.”

The review also stated that in general, vitamins A, B6, B12, C, E, folate and trace minerals such as iron, zinc, selenium, and copper are vital in reducing the risk of infections and supporting immune function. Ensuring a healthy diet containing these essential vitamins and minerals, or supplementing when dietary sources are inadequate, may be helpful in preventing illness. Gut health is also important in maintaining a healthy immune system. Consuming fermented foods and a diet rich in fiber can help to maintain a healthy gut microbiota.

Treatments

According to the CDC, most people who become ill with COVID-19 will not require any specific treatment. Over- the-counter fever and pain reducers are advised to relieve aches and pains associated with illness. Ensuring adequate hydration and rest are also considered important for recovery.35

Early in-home treatment options have been recommended by researchers and physicians globally, however, many countries, including the U.S., have failed to recommend early treatment options. The “wait and see” approach has been criticized by many physicians who believe that precious time has been wasted when patients are told to monitor symptoms instead of being provided with potential life-saving therapeutics. Multiple treatment protocols have been utilized globally, with physicians reporting positive patient outcomes.36

On February 7, 2022, the CDC updated its guidelines to recommend that individuals with one or more underlying health conditions contact a health care provider immediately following a positive COVID-19 test as treatments may be available and early intervention was most effective.37

FDA-Approved Treatments

On October 22, 2020, the FDA approved Remdesivir, for use in COVID-19 patients 12 years of age and older and who weigh at least 88 pounds. Remdesivir, an antiviral medication administered intravenously, must be given in an acute care setting such as a hospital or similar facility. The drug initially received Emergency Use Authorization (EUA) by the FDA on May 1, 2020, and clinical studies on safety and effectiveness for use in younger populations are still ongoing.38

Developed by Gilead Sciences in conjunction with the CDC and the U.S Army Medical Research Institute of Infectious Diseases (USAMRIID), Remdesivir was initially used as a potential treatment against ebolavirus but found to be ineffective. Preliminary studies on its use in the treatment of COVID-19 report the medication to speed up recovery time by 31 percent.39

According to the FDA, one randomized, double-blind, placebo-controlled clinical trial conducted by the National Institute of Allergy and Infectious Diseases (NIAID) on recovery rates of persons hospitalized with COVID-19 reported faster recovery times in persons receiving Remdesivir when compared to the placebo group. The FDA press release noted that persons receiving the drug recovered on average in 10 days compared to 15 days for those in the placebo group.

Two additional clinical trials reported improvements in persons receiving Remdesivir when compared to the placebo, however results were not considered statistically significant. This includes one trial that looked at the drug’s effects on reducing mortality rates.

In mid-October 2020, the World Health Organization (WHO) reported that preliminary results of a larger international study found that Remdesivir “appeared to have little or no effect on hospitalized COVID-19.”40

On November 13, 2020, Jozef Kesecioglu, president of the European Society of Intensive Care Medicine, stated that “remdesivir is now classified as a drug you should not use routinely in COVID-19 patients.”41

A study published in the Journal of the American Medical Association (JAMA) in July 2021 concluded that:42

“remdesivir treatment was not associated with improved survival but was associated with longer hospital stays. Routine use of remdesivir may be associated with increased use of hospital beds while not being associated with improvements in survival.”

This study was followed by another published on September 14, 2021 in the Lancet which concluded that:43

“No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support.”

On January 21, 2022, the FDA approved use of Remdesivir in the outpatient setting for persons 12 years and older with mild to moderate SARS-CoV-2 infection who are considered at high risk of progressing to severe illness. Additionally, an EUA was issued for the drug to be used in COVID-19 positive infants weighing at least 3.5 kilograms who are considered at high risk for severe illness.44

Remdesivir received full FDA approval for use in children 28 days and older and at least 3 kilograms hospitalized for COVID-19 or not hospitalized but considered at high risk for developing severe illness.45 Approval of Remdesivir in infants and young children was based on an open label study of only 53 children, with no placebo control. In the study, 72 percent of children suffered adverse events, with 21 percent of serious adverse events considered to be unrelated to the medication. Three children died during the study, from COVID-19 or a pre-existing condition. Study results to support the drug’s approval have not been published, and the trial is ongoing with a scheduled end date of February 2023.46

Treatments approved under Emergency Use Authorization (EUA)

Emergency Use Authorization (EUA) is a status given to experimental products by the FDA during a public health emergency, as defined under federal law.47 48

On November 19, 2020, the FDA issued an EUA for the drug baricitinib, to be administered in combination with Remdesivir, for the treatment suspected or confirmed COVID-19 illness in hospitalized persons two years of age and older who are also receiving oxygen, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.

Baricitinib is an FDA approved medication for the treatment of moderate to severe rheumatoid arthritis. In a clinical trial involving 1,033 patients, patients who received baricitinib in combination with Remdesivir recovered on average in seven days, whereas those who received Remdesivir with a placebo recovered in eight days. Additionally, this trial reported higher survival rates in persons who received baricitinib and Remdesivir when compared to those who received only Remdesivir.49

The FDA also issued an EUA for the experimental drug bamlanivimab in November 2020,50 51 which has been developed specifically for COVID-19 illness and is a monoclonal antibody therapy. Under the EUA, bamlanivimab was authorized for use in persons 12 years of age and older considered at a high-risk for severe COVID-19 illness and/or hospitalization. According to the FDA:

“Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful antigens such as viruses. Bamlanivimab is a monoclonal antibody that is specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells.”

In a clinical trial involving 465 non-hospitalized adults with mild to moderate COVID-19 symptoms, only three percent of persons who received bamlanivimab required hospitalization or emergency room treatment compared to ten percent of those in the placebo arm. Bamlanivimab was not permitted for use in persons receiving oxygen or hospitalized for COVID-19 disease because use of the drug was associated with more severe outcomes. On April 16, 2021, the FDA revoked the EUA that permitted bamlanivimab to be administered alone, stating that the increase in SARS-CoV-2 variants had resulted in an increase in treatment failure. According to the press release, the FDA reported that the known and potential benefits of bamlanivimab, when administered alone, no longer outweighed the known and potential risks for its authorized use.52

Two additional experimental monoclonal antibodies, casirivimab53 and imdevimab,54  received EUA approval on November 21, 2020, to be given in combination to persons 12 years of age and older who had tested positive for SARS-CoV-2 and were considered at high-risk for severe COVID-19 illness. The use of these medications, however, was limited to persons who were not hospitalized or requiring oxygen therapy due to COVID-19. If administered to persons hospitalized and receiving high flow oxygen or mechanical ventilation for COVID-19, outcomes may be worse.55 This antibody cocktail, known as Regeneron, was used in mid-October to treat former President Donald Trump even though it had not yet been granted EUA approval. 56

On February 9, 2021, the FDA issued an EUA for bamlanivimab and etesevimab administered simultaneously for the treatment of mild to moderate COVID-19 in persons 12 years of age and older who tested positive for SARS-CoV-2 and who were at high risk for progressing to severe COVID-19 illness.57 Etesevimab is also an experimental monoclonal antibody developed specifically to treat COVID-19 illness.58 The FDA reported that a single intravenous infusion dose of bamlanivimab and etesevimab administered together significantly reduced COVID-19-related hospitalization and death based on data collected during 29 days of follow-up when compared to placebo. The safety and effectiveness of this treatment protocol continues to be under evaluation.59 The EUA was expanded to include young children and newborns on December 3, 2021.60

On May 26, 2021, the FDA authorized the use of the investigational monoclonal antibody therapy sotrovimab as a treatment of mild-to-moderate COVID-19 in persons 12 years and older. The treatment, however, is not authorized for use in persons who are hospitalized or receiving oxygen therapy for COVID-19 illness.61

The FDA, however, revised the EUAs for bamlanivimab and etesevimab (administered together) and casirivimab and imdevimab (REGEN-COV) and restricted use of these products on January 24, 2022. According to the FDA, these monoclonal antibodies were considered unlikely to be effective against the Omicron variant and were no longer authorized for use in any U.S. states, jurisdictions, or territories.62

On February 11, 2022, the FDA issued an EUA for bebtelovimab, a monoclonal antibody, for the treatment of the Omicron variant of COVID-19. Bebtelovimab is authorized for persons 12 years and older, weighing at least 40 kilograms, who are considered at high risk of progressing to severe COVID-19 illness. This treatment is only available in an out-patient setting for individuals who do not require oxygen therapy.63

Oral Anti-Viral Medications

In December 2021, the FDA authorized the use of two oral anti-viral medications, Paxlovid and molnupiravir, for the treatment of COVID-19 illness.

Paxlovid, manufactured by Pfizer, is recommended for use in children 12 years and older who are positive for SARS-CoV-2 and at high risk for severe disease. The medication is recommended to be given as soon as a diagnosis is made and within five days of symptom onset.

Side effects of the medication include diarrhea, impairment of taste, high blood pressure, and muscle aches. One of the components of Paxlovid, Ritonavir, can cause liver damage. This medication may also lead to HIV-1 drug resistance in persons with undiagnosed or uncontrolled HIV-1. The medication is not recommended for use in persons with kidney or liver disease. According to the FDA, an analysis of the medication in 1,039 individuals reported a 0.86 fatality rate in persons who received Paxlovid, compared to the placebo group (1,046 individuals) that reported a 6 percent death rate. Studies on the medication are ongoing.64 Paxlovid has the potential to cause severe or life-threatening reactions if taken with common medications such as antidepressants, anticoagulants, and statins.65

A case study pending peer review posted in April 2022 reported on a 71-year-old male who recovered quickly from COVID-19 illness but experienced an increase in viral loads and symptomatic illness nine days after his initial COVID-19 positive test.66 In May 2022, the CDC issued an emergency alert to health care providers regarding the risk of “rebound” COVID-19 infection in individuals treated with Paxlovid. The alert stated that additional treatment with Paxlovid was not recommended and those experiencing a relapse in symptoms should re-isolate for at least five days and wear a mask for at least ten days.67 In the summer of 2022, several individuals, including Dr. Anthony Fauci,68 President Joe Biden,69 and First Lady Jill Biden70 reported rebound COVID-19 infection after taking Paxlovid.

In late April 2022, Pfizer announced that Paxlovid did not prevent symptomatic COVID-19 illness in household contacts of persons who took the medication.71

Molnupiravir, manufactured by Merck, is authorized for use in adults 18 years and older for the treatment of COVID-19 illness who are positive for SARS-CoV-2 and at risk of severe illness. According to clinical trials, of the 709 individuals who received molnupiravir, 6.8 percent required hospitalization compared to 9.7 percent of the 699 individuals who received the placebo. One person who received molnupiravir died, compared to nine people who received the placebo. This experimental medication is not recommended for use in pregnant women because animal reproductive studies appear to indicate a risk of fetal harm. Reported side effects include diarrhea, nausea, and dizziness.72

Molnupiravir is capable of mutating RNA, which has some scientists expressing concerns that the medication could potentially cause new virus variants which may be deadlier.73

Additional Treatments

High doses of vitamin C given intravenously (IV) have been used to treat COVID-19. Three clinical trials and several smaller studies reported successful outcomes among patients who received IV vitamin C at doses varying from 50 to 200 milligrams per kilogram of body weight to up to 200 mg per kg per day.74

One study published in March 2020 reported:

“High-dose intravenous VC has also been successfully used in the treatment of 50 moderate to severe COVID-19 patients in China. The doses used varied between 10 g and 20 g per day, given over a period of 8–10 h. Additional VC bolus may be required among patients in critical conditions. The oxygenation index was improving in real time and all the patients eventually cured and were discharged.”75

The Frontline COVID-19 Critical Care Alliance (FLCCC), a group comprised of highly published critical care experts, have outlined a protocol to treat hospitalized COVID-19 patients. In February 2021, the FLCCC’s clinical and scientific rationale on their methylprednisolone, ascorbic acid (vitamin C), thiamine, heparin and co-interventions (MATH+) protocol was peer reviewed and published in Journal of Intensive Care Medicine.[76 The protocol was reported as effective in the treatment of severe COVID-19 illness requiring hospitalization. Additional treatment co-interventions noted in the research article included the use of melatonin, famotidine, atorvastatin, vitamin D3, and the application of therapeutic plasma exchange (a treatment that replaces an individual’s blood plasma).77

The article noted that systematic use of MATH+ in two U.S. hospitals demonstrated an absolute mortality risk reduction of more than 75 percent, or 5.1 percent vs. 22.9 percent, when compared to multiple published COVID-19 hospital mortality rates in the U.S. The article concluded:

“It is exceedingly unlikely that a “magic bullet” will be found, or even a medicine which would be effective at multiple stages of the disease. The Math+ treatment protocol instead offers an inexpensive combination of medicines with a well-known safety profile based on strong physiologic rationale and an increasing clinical evidence base which potentially offers a life-saving approach to the management of COVID-19 patients.” 78

Use of Anti-Malaria Medications

In March 2020, two anti-malaria medications, hydroxychloroquine and chloroquine, received EUA authorization to treat COVID-19. The EUA was issued based on laboratory studies that showed these medications to be effective against coronaviruses. Use of these medications, however, quickly became controversial.

On May 22, 2020, The Lancet published a study reporting that hydroxychloroquine was not effective against COVID-19 and was associated with heart arrhythmias and higher death rates. As a result of this study, the World Health Organization (WHO) halted their hydroxychloroquine drug trials. The validity of this study, however, was immediately questioned and when the study data could not be obtained for independent review, The Lancet was forced to retract the study.79

Scientists affiliated with the Henry Ford Hospital System in Detroit, Michigan published research on hydroxychloroquine that reported the medication to be effective in reducing the COVID-19 death rate. No heart-related side effects were reported, and outcomes improved when treatment was initiated early.80 The study results, however, have been criticized by health officials including Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID).81 Hydroxychloroquine administered in combination with zinc and azithromycin has also been reported to be an effective treatment for hospitalized COVID-19 patients.82 The FDA, however, revoked the EUA for hydroxychloroquine in mid-June 2020, stating that the medication was ineffective against COVID-19 and potentially harmful.83

A January 2021 published study in the American Journal of Medicine reported that when the medicine was administered early in the treatment stage, it was effective at halting disease progression, preventing hospitalization, and reducing mortality rates. This study also reported the effectiveness of using the hydroxychloroquine in combination with either azithromycin or doxycycline, two commonly prescribed antibiotics.84

Off-Label Use of Other Drugs

Ivermectin, a medication used to treat parasites, has been found to inhibit SARS-CoV-2, the virus that causes COVID-19, in vitro.85 Australian gastroenterologist Dr. Thomas Borody, known for developing the first peptic ulcer cure, reported that ivermectin administered in conjunction with zinc and the antibiotic doxycycline could be a ‘potential life-saver.’86 A January 2021 published study reported that the use of ivermectin was associated with lower rates of death, especially in patients who had severe pulmonary involvement.87 A journal study published in April 2021 concluded that:88

“Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.”

Despite published data to support the use of ivermectin as a treatment for COVID-19, the medication has not been granted approval or authorization by the FDA. On August 26, 2021, the CDC issued a health advisory regarding the use of ivermectin as a treatment option for COVID-19. In the health advisory, the CDC noted that the medication, while FDA-approved for use as a safe treatment option for infections caused by internal and external parasites, was not approved or authorized as a COVID-19 treatment. The CDC warned against use of the medication, and included a warning about the risk of ingesting topical formulation as well as products intended for veterinarian use.89

Multiple studies have found ivermectin to be effective in treating COVID-19 illness, preventing hospitalization, and reducing mortality.90

The corticosteroid Budesonide, commonly used to treat asthma symptoms, has also been successfully used to treat symptoms of COVID-19. According to a study conducted by the University of Oxford, budesonide significantly decreased urgent care visits and hospitalizations, and when used within seven days of symptom onset, recovery time was decreased. Fever, illness symptoms, including persistent illness symptoms, resolved quicker in study participants who received budesonide.91

Additional medications that have shown as effective early treatment options for COVID-19 illness include fluvoxamine, 92 93 94 a medication typically used to treat depression, and fenofibrate, a medication used to decrease cholesterol 95 96

Blood plasma donated from individuals who have recovered from COVID-19 was also studied as potential treatment option. In early August 2020, Mayo Clinic researchers reported that this therapy was helpful despite a lack a formal data to support its use.97 A study on the use of convalescent plasma to treat moderate COVID-19 illness in adults in India published in the British Medical Journal in October 2020, however, reported that this treatment was not effective in reducing the progression to severe disease or preventing COVID-19 related deaths.98

On February 4, 2021, the FDA revised the convalescent plasma EUA to limit it to the use of only high-titer convalescent plasma for early treatment of hospitalized patients or in persons with impaired humoral immunity who are unable to produce an adequate antibody response. Low-titer convalescent plasma was declared ineffective and its use was no longer authorized.99

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

What is COVID-19 vaccine?

Coronaviruses are a group of diverse, single-stranded, enveloped RNA viruses that cause a wide range of respiratory, gastrointestinal and neurologic illnesses with varying severity in animals and humans. Most coronaviruses, including those causing the common cold, are not associated with significant mortality, with the exception of Severe Acute Respiratory Syndrome (SARS), which emerged in China in 2002, the coronavirus causing Middle East Respiratory Syndrome (MERS), which was identified in Jordan and Saudi Arabia in 2012,1 and SARS-CoV-2, new novel coronavirus, which was initially identified in Wuhan City, in the Hubei province of China.2 In the U.S., there are no FDA-licensed vaccines targeting SARS, MERS or any of the four common coronaviruses.

Immediately after the January 30, 2020 WHO declaration that a novel coronavirus outbreak in China posed a “public health emergency of international concern,” the Gates Foundation3 and World Health Organization (WHO)4 issued press releases informing the world that experimental coronavirus vaccines already in development would be put on a fast track to licensure for global use.

In May 2020, Former President Donald Trump announced the rollout of Operation Warp Speed, a plan to develop, manufacture, and distribute millions of COVID-19 vaccine doses by the end of 2020.5 According to the National Institute of Allergy and Infectious Diseases (NIAID):

“Operation Warp Speed is a partnership among several federal government agencies to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics, including the specific goal of delivering 300 million doses of a safe, effective vaccine for COVID-19 by January 2021.

Notably, Operation Warp Speed will manufacture promising candidate vaccines at an industrial scale before efficacy and safety are confirmed through Phase III trials. Doing so will significantly shorten the timeline for distribution as compared to traditional vaccine development, should the trials succeed.” 6

New ways to make vaccines including new technologies and production platforms quickly became favored over the older traditional ways to make vaccines in the COVID-19 vaccine race.7 8 

Traditional vaccines contain attenuated (live) or inactivated (killed) viruses or bacteria or selected proteins, as well as adjuvants, such as aluminum, to stimulate an immune response that produces artificial immunity. For example, older viral vaccines for smallpox and measles vaccine contain live attenuated viruses; injectable influenza vaccines contain inactivated viruses; the recombinant hepatitis B virus vaccine is a protein subunit vaccine, while the newer human papillomavirus (HPV) virus vaccine contains virus-like particles.9

For the past two decades, researchers have been experimenting with gene-based technology platforms, notably ones that introduce foreign DNA and RNA into cells of the body, to develop experimental vaccines for SARS, MERS, HIV and other diseases.10

 

Pre-licensing Clinical Trial Process

According to the U.S Food and Drug Administration (FDA), pre-licensing clinical trials are generally conducted in three phases. Phase 1 trials are the initial human studies involving a small number of individuals to test for safety and immune response. Phase 2 studies usually enroll a slightly larger number of subjects and focuses on selecting the product’s dosage. The final pre-licensing study, Phase 3, collects data on the experimental product’s effectiveness and safety. The FDA reports that Phase 3 trials typically involve thousands of subjects.11

Double-blind, randomized, placebo-controlled trials (RCTs) are considered the most reliable research method. In these studies, one group of subjects receives the experimental product being tested while the other group receives a placebo designed to appear as similar as possible to the product being studied. Individuals in both groups do not know whether they are receiving the experimental product or the placebo. Additionally, the researchers conducting the trials are also not made aware about which group is receiving which treatment (making it a "double-blind" experiment). This is important, as it prevents the researchers from unconsciously biasing their evaluation of the results or unintentionally tipping off the study participants.12

If pre-licensing clinical trials are considered successful, the manufacturer can submit a Biologics License Application (BLA). This application must include safety and efficacy data and contain enough information to allow the FDA review team to decide on whether to approve or deny a vaccine. Once the application is reviewed by the FDA, the manufacturer along with the FDA may present their information to the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC). This committee is comprised of non-FDA scientists, physicians and others whose charge is to provide advice to the FDA on the data provided in a public forum. The FDA, however, has the option to disregard any feedback it receives from VRBPAC.13

Typically, it takes several years, if not decades, for pharmaceutical companies to develop, test, and receive approval for a new vaccine. The fastest timeline to date for a vaccine to complete all stages of clinical development, pre-licensing clinical trials and FDA-approval has been four years.14

On June 30, 2020, the FDA announced that a COVID-19 vaccine would only receive approval, if it were at least 50 percent more effective than a placebo at either preventing illness or reducing its severity.15

The FDA released its guidance for industry regarding Emergency Use Authorization (EUA) approval for COVID-19 vaccines on October 6, 2020, and stated that it would be requiring that at least half of all Phase 3 clinical trial participants be followed for at least two months following administration of the second vaccine dose. The FDA also requested that vaccine manufacturers submit information on a minimum of five cases of severe COVID-19 disease among individuals who received the placebo.16

However, vaccine trial designs have faced criticism and in October of 2020 the British Medical Journal (BMJ) noted that Phase 3 trials for Moderna, Pfizer, AstraZeneca COVID-19 vaccines will not answer basic questions around preventing infection and reducing the likelihood of severe illness.17

A September 2020 article in Forbes by noted biologist William Haseltine, PhD18 revealed that COVID-19 vaccine studies by Moderna, Pfizer, AstraZeneca, and Johnson & Johnson intend “to complete interim and primary analyses that at most include 164 participants.” 19

According to Dr. Haseltine, with an efficacy success requirement of 70 percent, this equates to interim analysis based on the results of infection ranging from 32 (Moderna) vaccine to 77 (Johnson & Johnson) vaccine recipients. Dr. Haseltine concluded by saying that COVID-19 vaccine trials were in essence designed to succeed. The article also contained many of the same concerns noted in the October 2020 BMJ article and added that “vaccines currently under trial will not be the silver bullet” ending the pandemic.20

 

Emergency Use Authorization

According to the FDA, vaccine makers may submit an application to have their products approved under an Emergency Use Authorization (EUA). Under EUA authority, the FDA Commissioner may permit “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN (CBRN = chemical, biological, radiological, nuclear) threat agents when there are no adequate, approved, and available alternatives.”21 To learn more about EUA products and vaccines and consumer rights, visit NVIC’s FAQ on Emergency Use Vaccines (EUA) & Vaccine Injury Compensation.

In December 2020, two experimental messenger RNA COVID-19 vaccines developed and produced by Pfizer - BioNTech and Moderna with NIAID were granted an EUA by the FDA to release the vaccines for use in the U.S.22 23 Messenger RNA (mRNA) vaccines are gene based vaccines that involve injecting lipid nanoparticles containing mRNA (genetic code) that enable the vaccine to get past the cell wall, into the intracellular space, then causes the cell’s ribosome to make viral proteins (antigen that stimulate the immune system.)24 In essence, an mRNA vaccine tricks the body into producing the viral proteins to trigger an immune response.25 Messenger RNA vaccines can be produced in the lab using faster and less expensive processes than traditional vaccines.26

On February 27, 2021, the FDA granted an Emergency Use Authorization to Johnson & Johnson and Janssen Pharmaceutical Companies for a non-replicating viral vaccine. This experimental vaccine uses an adaption of human adenovirus 26 (Ad26), which causes common colds, to transport the SARS-CoV-2 spike protein code into the body to trigger an immune response.27 28 29

The FDA issued an Emergency Use Authorization to Novavax for an experimental COVID-19 vaccine using recombinant nanoparticle technology on July 13, 2022.30 Referred to as a protein subunit vaccine,31 this vaccine contains Novavax’s patented saponin-based Matrix-M™ adjuvant designed to enhance the immune response and stimulate high levels of neutralizing antibodies.32

 

Pfizer - BioNTech mRNA COVID-19 Vaccine Approval

On August 23, 2021 the FDA licensed and granted EUA status to Comirnaty COVID-19 vaccine, an mRNA vaccine developed by BioNTech, for use in persons 16 years of age and older.33 The FDA also stated that use of Comirnaty and the experimental Pfizer-BioNTech mRNA COVID-19 vaccine are interchangeable due to having the same formulation.34 35  However, the FDA also stated that the Pfizer-BioNTech experimental vaccine and the BLA approved Comirnaty were legally distinct, but did not disclose how and why the two vaccines are legally distinct. 36 37  

Following FDA approval of Comirnaty in August 2021, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended use of the 2-dose vaccine series in persons 16 years of age and older.38 The FDA licensed Comirnaty for use in teens 12 through 15 years in July 2022.39

When a product receives a priority review designation by the FDA, the decision to take action on the application is usually done within six months.40 In the case of the Pfizer – BioNTech vaccine, the decision to grant full approval was completed in less than four months.41

Prior to granting approval of Comirnaty, the FDA declined to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting42 despite previously stating that they were committed to use an advisory committee composed of independent experts to ensure deliberations about authorization or licensure are transparent for the public.”43

In the Summary Basis for Regulatory Action Document published to support approval of Comirnaty, the FDA reported that it “did not refer this application to the VRBPAC because our review of the information submitted to this BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.”44

The Pfizer-BioNTech mRNA COVID-19 vaccine was initially issued an EUA by the FDA on December 11, 2020 for use in persons 16 years of age and older.45 The FDA expanded the EUA to include adolescents 12 and older on May 10, 2021.46

According to the Fact Sheet provided by the FDA,47 the Comirnaty /Pfizer-BioNTech COVID-19 Vaccine is manufactured and made available as a frozen suspension in vials that contain multiple doses. Each individual vial must be diluted with 1.8 ml of sterile 0.9 percent Sodium Chloride injection, USP, before use.

Each dose contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) that encodes the viral spike (S) glycoprotein of SARS-CoV-2. Additional vaccine ingredients include lipids (0.43 mg (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene glycol)-2000- N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg cholesterol), 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.01 mg potassium chloride, 6 mg sucrose, and 0.07 mg dibasic sodium phosphate dihydrate. The 0.9 percent Sodium Chloride Injection, USP adds another 2.16 mg sodium chloride per dose.

This vaccine does not contain a preservative and the vaccine vial stoppers are free of latex.

Additionally, the Comirnaty/Pfizer-BioNTech Fact Sheet states:

“The modRNA in the Pfizer-BioNTech COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.” 48

On December 16, 2021, the FDA approved a change to the ingredients of Pfizer’s Comirnaty vaccine. The ingredient, Tris, is a buffer that, according to the FDA, will permit the vaccine to be more stable at refrigerator temperatures for long periods of time.49

The Comirnaty/Pfizer-BioNTech COVID-19 vaccine is recommended to be given intramuscularly (IM) as a two-dose series administered three weeks apart. The CDC also states that the interval time between the first and second dose can be extended to eight weeks. The increase in interval time was based on data suggesting that an increase in interval time might decrease the risk of heart inflammation. Males between the ages of 12 and 39 are considered at highest risk for myocarditis.50 51

There is no available data on the interchangeability of the Comirnaty/Pfizer-BioNTech COVID-19 Vaccine with other COVID-19 vaccines to complete the two-dose vaccination series. Persons who have received one dose of Comirnaty/Pfizer-BioNTech COVID-19 Vaccine should complete the series by receiving a second dose of Comirnaty/Pfizer-BioNTech COVID-19 Vaccine.52

There is no data available on the co-administration of the Comirnaty/Pfizer-BioNTech Vaccine with any other vaccine product.53

The duration of vaccine-acquired immunity from Pfizer-BioNTech’s COVID-19 vaccine is not known. It is also not known whether this vaccine can reduce or stop transmission of the virus. This means that vaccinated individuals may still be capable of transmitting the virus to others.54

There is insufficient data to support the use of Pfizer-BioNTech’s COVID-19 vaccine in persons who were previously infected with SARS-CoV-2. In clinical trials, there was one case of COVID-19 illness in both the vaccine group and the placebo group in persons who were found to be positive for SARS-CoV-2 at baseline. Based on the limited data of this sub-population provided to the FDA by Pfizer-BioNTech, the vaccine efficacy in this population was reported at -7.1 percent (Confidence Ratio -8309.9, 98.6).55

The Pfizer-BioNTech COVID-19 vaccine is recommended to be shipped and stored between -80ºC to -60ºC (-112ºF to -76ºF) and protected from light until ready to use.56 On February 25, 2021, the FDA announced that frozen undiluted vials of the Pfizer-BioNTech COVID-19 could also be transported and stored at temperatures typically found  in pharmaceutical freezers for up to 14 days.57 Temperature storage and shipping guidelines were updated again on May 19, 2021, which permitted undiluted, thawed vaccines to be stored at refrigerator temperatures, 2°C to 8°C (35°F to 46°F), for up to 1 month.58

Mishandling of the vaccine during any step of the distribution process may result in an ineffective vaccine product. 59

Pfizer – BioNTech mRNA COVID-19 Pediatric Vaccine

On October 29, 2021, the FDA authorized use of a 10 mcg dose of Pfizer-BioNTech mRNA COVID-19 vaccine for children 5 through 11 years of age.60

According to the Fact Sheet provided by the FDA,61 each 0.2 ml dose of Pfizer-BioNTech COVID-19 Vaccine contains 10mcg of nucleoside modified messenger RNA (mRNA) that encodes the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus. The multidose vials with orange caps and labels with orange borders must be diluted with 1.3ml of sterile 0.9 percent sodium chloride prior to use.

Each dose also contains a total lipid content of (0.14 mg (4- hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.03 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.06 mg cholesterol), 0.02 mg 2[(polyethylene glycol)-2000- N,N-ditetradecylacetamide,10.3 mg sucrose, 0.02 mg tromethamine, and 0.13 mg tromethamine hydrochloride. The vaccine also contains 0.9mg sodium chloride per dose. The vaccine vial stoppers are free of latex and the vaccine does not contain a preservative.

According to the FDA:62

“To provide a vaccine with an improved stability profile, the Pfizer-BioNTech COVID-19 Vaccine for use in children 5-11 years of age uses tromethamine (Tris) buffer instead of the phosphate buffered saline (PBS) as used in the previous formulation and excludes sodium chloride and potassium chloride. The packaged vials for the new formulation are stored frozen at -90°C to - 60°C. The frozen vials may be thawed and stored at refrigerator at 2°C to 8°C for up to 10 weeks.”

The vaccine is recommended to be administered intramuscularly (IM) as a two-dose primary series, three weeks apart. There is no data on the safety or effectiveness of administering the Pfizer-BioNTech vaccine with any other vaccine.

On November 2, 2021, the CDC’s ACIP voted to approve use of the 10mcg dose of the Pfizer-BioNTech COVID-19 vaccine in all children 5 through 11 years of age.63 An additional dose of the Pfizer-BioNTech COVID-19 pediatric vaccine was also authorized for use in moderately or severely immunocompromised children, to be administered 28 days after the second vaccine dose.64 65 In May 2022, ACIP voted to recommend that all children 5 through 11 years receive a booster dose of COVID-19 vaccine to be administered five months after completion of the 2-dose vaccine series.66

Pfizer – BioNTech mRNA COVID-19 Vaccine for Infants and Young Children

On June 17, 2022, the FDA issued an EUA for a 3mcg dose of Pfizer-BioNTech mRNA COVID-19 Vaccine for infants and young children aged 6 months through 4 years of age.67

According to the Fact Sheet provided by the FDA,68 the vaccine is supplied in a maroon colored capped multi-dose vial and labeled with maroon borders. The frozen vaccine suspension must be diluted with 2.2 mL of sterile 0.9 percent sodium chloride prior to use. Each 0.2 mL dose of the vaccine contains 3mcg of nucleoside modified messenger RNA (mRNA) that encodes the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus.

Each dose also contains the following ingredients: 3.2 mg sucrose, 0.006 mg tromethamine, 0.04 mg tromethamine hydrochloride; lipids (0.04 mg ((4- hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.005 mg 2[(polyethylene glycol)-2000- N,N-ditetradecylacetamide, 0.01 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.02 mg cholesterol). The sterile 0.9 percent sodium chloride diluent adds 1.52 mg of sodium chloride per dose. The vaccine vial stoppers are free of latex and the vaccine does not contain a preservative.69

The vaccine is recommended to be administered intramuscularly (IM) as a three-dose primary series, with the first two doses administered three weeks apart, followed by a third dose at least 8 weeks after the second dose. There is no data on the safety or effectiveness of administering the Pfizer-BioNTech COVID-19 vaccine with any other vaccine.70

The CDC’s ACIP voted to recommend use of the Pfizer-BioNTech mRNA COVID-19 vaccine for all children 6 months through 4 years of age on June 18, 2022. The recommendation also included infants and young children with a prior history of COVID-19 infection.71

Pfizer-BioNTech Monovalent Booster Doses

Prior to August 31, 2022, the CDC and FDA recommended that all persons 5 years and older receive a booster dose of the primary COVID-19 vaccine, to be administered five months following receipt of the second Pfizer-BioNTech COVID-19 vaccine dose. Individuals 50 years of age and older were also advised to receive a second booster dose, at least four months following receipt of the first booster dose. Persons with immunosuppressive conditions were also advised to receive an additional vaccine dose.72

On August 31, 2022, the FDA revoked the booster dose EUA recommendation for the Pfizer-BioNTech monovalent mRNA COVID-19 vaccine targeting the original Wuhan strain for all persons 12 years of age and older, and authorized use of a bivalent COVID-19 vaccine containing both the original strain and the Omicron variant.  As of August 31, 2022, the Pfizer-BioNTech mRNA COVID-19 vaccine remains authorized for use as a primary series and as a booster dose in children five through 11 years.73

Individuals who received a primary series of the Pfizer-BioNTech COVID-19 vaccine may opt to receive a different mRNA COVID-19 vaccine as a booster dose.74 There is limited safety and effectiveness data to support the use of a mix and match COVID-19 vaccination schedule.75

Pfizer-BioNTech Bivalent Booster Doses

The FDA authorized a bivalent dose of Pfizer-BioNTech mRNA COVID-19 vaccine containing the original Wuhan strain and the Omicron variant on August 31, 2022, to be administered as a single booster dose for all persons 12 years and older. This vaccine is recommended to be given two months following the original primary series or any booster dose.76

Each 0.3mL dose of the bivalent Pfizer-BioNTech COVID-19 Vaccine contains 15 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of original SARS-CoV-2 Wuhan-Hu-1 strain and 15 mcg of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron BA.4/BA.5 variant. The S-proteins of the SARS-CoV-2 BA.4 and BA.5 Omicron variant are identical. Each dose contains 30 mcg modRNA. Each 0.3 mL dose of the Bivalent Pfizer-BioNTech COVID-19 Vaccine supplied in single dose and multiple dose vials also contains: 0.05 mg 2[(polyethylene glycol)-2000-N, lipids (0.43 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1- diyl)bis(2-hexyldecanoate), N-ditetradecylacetamide, 0.09 mg 1,2- distearoyl-sn-glycero-3-phosphocholine, and 0.19 mg cholesterol), 0.4 mg tromethamine hydrochloride, 0.06 mg tromethamine, and 31 mg sucrose. The bivalent Pfizer-BioNTech COVID-19 Vaccine does not contain preservative and the vial stoppers are not made with natural rubber latex.77

 

Moderna mRNA COVID-19 Vaccine

Moderna mRNA COVID-19 Vaccine Approval

On January 31, 2022, the FDA licensed and granted EUA status to Spikevax COVID-19 vaccine, an mRNA vaccine developed by Moderna, for use in persons 18 years of age and older. The FDA also stated that use of Spikevax and the experimental Moderna mRNA COVID-19 vaccine are interchangeable due to having the same formulation. 78

Following FDA approval of Spikevax in January 2022, the CDC’s ACIP recommended use of the vaccine in persons 18 years of age and older.79

Prior to granting approval of Spikevax, the FDA declined to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting80 despite previously stating that they were committed to use an advisory committee composed of independent experts to ensure deliberations about authorization or licensure are transparent for the public.”81

In the Summary Basis for Regulatory Action Document published to support approval of Spikevax, the FDA reported that the most critical issues pertaining to vaccine safety were discussed by VRBPAC during meetings conducted October 2020, December 2020, and October 2021. According to the FDA, the assessment of the information had no impact on the risk/benefit considerations that would prompt the need for VRBPAC’s input on the vaccine’s licensure decision in persons 18 years of age and older.82

The Moderna mRNA COVID-19 vaccine was initially issued an EUA by the FDA on December 18, 2020 for use in persons 18 years of age and older.83

According to the Fact Sheet provided by the FDA,84 each 0.5 ml dose of Moderna’s COVID-19 Vaccine contains 100 mcg of nucleoside modified messenger RNA (mRNA) that encodes the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus.

Each dose also contains a total lipid content of 1.93 mg (SM-102, polyethylene glycol [PEG 2000 dimyristoyl glycerol [DMG, cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC), 0.31 mg tromethamine, 0.043 mg acetic acid, 1.18 mg tromethamine hydrochloride, 43.5 mg sucrose and 0.12 mg sodium acetate. This vaccine does not contain a preservative and the vaccine vial stoppers are free of latex.

Additionally, the Moderna Fact Sheet states:

“The nucleoside-modified mRNA in the Moderna COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.”85

Spikevax/Moderna COVID-19 Vaccine is recommended to be given as a two-dose series administered 28 days apart. The CDC also states that the interval time between the first and second dose can be extended to eight weeks. The increase in interval time was based on data suggesting that an increase in interval time might decrease the risk of heart inflammation. Males between the ages of 12 and 39 are considered at highest risk for myocarditis.86 87

There is no available data available on the interchangeability of the Moderna COVID-19 Vaccine with other COVID-19 vaccines to complete the two-dose vaccination series. Persons who have received one dose of Spikevax/Moderna COVID-19 Vaccine should receive a second dose of Spikevax/Moderna COVID-19 Vaccine to complete the vaccination series.88 89

There is no data available on the co-administration of the Spikevax/Moderna mRNA COVID-19 Vaccine with any other vaccine product.

The duration of vaccine-acquired immunity from Spikevax/Moderna’s COVID-19 vaccine is not known. The vaccine offers only minimal protection against infection and transmission. This means that vaccinated individuals can still become infected with the virus and spread it on to others.90

There is insufficient data on the use of Moderna’s COVID-19 vaccine in persons who are positive for SARS-CoV-2 at baseline. In clinical trials, there were no cases of COVID-19 illness in persons who were determined to be positive for SARS-CoV-2 at baseline in the vaccine group, and only one case among the SARS-CoV-2 positive individuals at baseline who were part of the placebo group.91

Moderna COVID-19 Vaccine for Adolescents

On June 17, 2022, the FDA issued an EUA to Moderna for its COVID-19 mRNA vaccine for use in adolescents aged 12 through 17 years of age.92

According to the Fact Sheet provided by the FDA,93 each 0.5mL dose of Moderna COVID-19 mRNA vaccine contains 100 mcg of nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus. This product is contained in a multi-dose vial with a red cap and labelled with a light blue border. Additional ingredients contained in the vaccine include 43.5 mg sucrose, 0.31 mg tromethamine, 1.18 mg tromethamine hydrochloride, 0.043 mg acetic acid, 0.20 mg sodium acetate trihydrate, and a total lipid content of 1.93 mg (SM-102, polyethylene glycol [PEG 2000 dimyristoyl glycerol [DMG, cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC).

The vaccine does not contain a preservative and the vaccine vial stopper does not contain natural latex rubber.94

The vaccine is recommended to be administered intramuscularly (IM) as a two-dose primary series, administered at least four weeks apart. There is no data on the safety or effectiveness of administering the Moderna COVID-19 vaccine with any other vaccine.95 As of June 25, 2022, adolescents aged 12 through 17 years who are considered moderately or severely immunocompromised are recommended to receive a third Moderna mRNA COVID-19 vaccine dose, to be administered at least four weeks after the second dose.96

The CDC’s ACIP voted to recommend use of the 100mcg dose of Moderna mRNA COVID-19 vaccine for all adolescents aged 12 through 17 years on June 23, 2022.97

Moderna COVID-19 Vaccine for Children

The FDA issued an EUA to Moderna on June 17, 2022 for their mRNA COVID-19 vaccine for use in children ages 6 through 11 years of age.98

According to the Fact Sheet provided by the FDA,99 each 0.5mL dose of Moderna COVID-19 mRNA vaccine contains 50 mcg of nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus. This product is contained in a multi-dose vial with a dark blue cap and labelled with a teal border. Additional ingredients contained in the vaccine include 43.5 mg sucrose, , 0.25 mg tromethamine, 1.2 mg tromethamine hydrochloride, 0.021 mg acetic acid, 0.10 mg sodium acetate trihydrate, and a total lipid content of 1.01 mg (SM-102, polyethylene glycol [PEG 2000 dimyristoyl glycerol [DMG, cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC).

The vaccine does not contain a preservative and the vaccine vial stopper does not contain natural latex rubber.100

The Moderna COVID-19 mRNA vaccine is recommended to be administered intramuscularly (IM) as a two-dose primary series, administered at least four weeks apart.101 Children aged 6 through 11 years of age who are considered immunocompromised are recommended to receive a third vaccine dose at least four weeks following the second dose.102

There is no data on the safety or effectiveness of administering the Moderna COVID-19 vaccine with any other vaccine.103

On June 23, 2022, the CDC’s ACIP voted to recommend use of the 50mcg dose of Moderna mRNA COVID-19 vaccine for all children 6 through 11 years of age.104

Moderna COVID-19 Vaccine for Infants and Young Children

On June 17, 2022, the FDA issued an EUA to Moderna for their mRNA COVID-19 vaccine for use in children ages 6 months through 5 years of age. 105

According to the Fact Sheet provided by the FDA,106 each 0.25mL dose of Moderna COVID-19 mRNA vaccine contains 25 mcg of nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus. This product is contained in a multi-dose vial with a dark blue cap and labelled with a magenta border. Additional ingredients contained in the vaccine include 21.8 mg sucrose, 0.13 mg tromethamine, 0.62 mg tromethamine hydrochloride, 0.011 mg acetic acid, 0.049 mg sodium acetate trihydrate, and a total lipid content of 0.5 mg (SM-102, polyethylene glycol [PEG 2000 dimyristoyl glycerol [DMG, cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC).

The vaccine does not contain a preservative and the vaccine vial stopper does not contain natural latex rubber.107

The vaccine is recommended to be administered intramuscularly (IM) as a two-dose primary series, administered at least four weeks apart. 108 Children aged 6 months through five years of age who are considered immunocompromised are recommended to receive a third vaccine dose at least four weeks following the second dose.109 There is no data on the safety or effectiveness of administering the Moderna COVID-19 vaccine with any other vaccine.110

On June 18, 2022, the CDC’s ACIP voted to recommend use of the 25mcg dose of Moderna mRNA COVID-19 vaccine for all children 6 months through 5 years of age. The recommendation also included infants and young children with a prior history of COVID-19 infection.111

Moderna COVID-19 Monovalent Booster Doses

Prior to August 31, 2022, the FDA, under EUA, authorized a 50mcg booster dose, or half dose, of the Moderna COVID-19 vaccine to be given six months following administration of the second vaccine dose.112 This vaccine was approved for use in October 2021 by the CDC in all persons 65 years of age and older, in persons 18 and older at risk for severe COVID-19 disease, and in persons 18 and older who live or work in a setting that puts them at an increased risk of exposure to SARS-CoV-2.113 This booster dose recommendation was expanded in November 2021 to all persons 18 years and older on November 19, 2021 who were previously vaccinated with two doses of an mRNA vaccine (Pfizer-BioNTech or Moderna). The booster dose was initially recommended at least six months following receipt of the second mRNA COVID-19 vaccine dose.114 115 On January 7, 2022, the interval between the second vaccine dose and the booster dose was shortened to five months.116

On March 29, 2022, a second booster dose was authorized by the FDA and recommended for all persons 50 years and older, to be given at least four months after the first booster dose. Immunocompromised individuals who received a 3- dose primary series and a single booster dose were also recommended to receive a second booster dose, at least four months after the initial booster dose.117 118

The FDA withdrew the EUA for the Monovalent booster dose on August 31, 2022 for all adults 18 and older when it authorized a single booster dose of a bivalent Moderna mRNA COVID-19 vaccine containing the original Wuhan strain and the Omicron variant.119

Moderna COVID-19 Bivalent Booster Doses

On August 31, 2022, the FDA issued an EUA to Moderna for a bivalent mRNA COVID-19 vaccine to be given as a single dose in persons 18 years and older. This dose is recommended at least two months following receipt of the primary series or booster dose.120

Moderna COVID-19 Vaccine, Bivalent is provided as a sterile white to off-white suspension for intramuscular injection. Each 0.5 mL booster dose of bivalent Moderna COVID-19 Vaccine contains 25 mcg nucleoside-modified messenger RNA (mRNA) encoding the prefusion stabilized Spike glycoprotein (S) of the SARS-CoV-2 Original Wuhan-Hu-1 strain and 25 mcg mRNA encoding the pre-fusion stabilized S-protein of the SARS-CoV-2 Omicron BA.4 and BA.5 variant. The BA.4 and BA.5 S-proteins of the SARS-CoV-2 Omicron variant lineages are identical. Each dose also contains the following ingredients: 0.25 mg tromethamine, 1.2 mg tromethamine hydrochloride, 0.021 mg acetic acid, 0.10 mg sodium acetate trihydrate, a total lipid content of 1.01 mg (SM-102, polyethylene glycol [PEG 2000 dimyristoyl glycerol [DMG, cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC), and 43.5 mg sucrose. The bivalent Moderna COVID-19 Vaccine does not contain a preservative and the vial stoppers are not made with natural rubber latex.121

 

Janssen/Johnson & Johnson COVID-19 Viral Vector Vaccine

Viral vector vaccines genetically engineer live viruses such as poxviruses and adenoviruses to include the SARS-CoV-2 spike protein code. The engineered viruses are then used as a vector, or delivery method, to get the altered genetic code inside the cell where the cell’s ribosome produces SARS-CoV-2 protein antigen that is recognized by immune system to elicit a protective immune response.122

On February 27, 2021, the FDA issued an EUA for Janssen/Johnson & Johnson’s experimental vaccine for use in persons 18 years of age and older.123 The CDC, however, gave a preferential recommendation to mRNA vaccines on December 16, 2021 due to the risk of TTS following vaccination.124 According to the CDC, the Janssen/Johnson & Johnson COVID-19 vaccine should only be used in cases where a person is unable to or unwilling to receive an mRNA vaccine, or in cases where no other option is available.125

Janssen/Johnson & Johnson’s experimental vaccine, Ad26.COV2.S, is a non-replicating viral vector vaccine that uses AdVac® and PER.C6® technologies.126 AdVac technology uses an adaptation of human Adenovirus 26 to transport the genetic code of the SARS-CoV-2 spike protein into the body to trigger an immune response.127 128 PER.C6 are proprietary cells owned by Janssen Pharmaceutical Companies that were developed in 1985 from retinal cells of an 18-week-old aborted fetus.129

Adenoviruses are “non-enveloped, double-stranded DNA viruses” that often cause mild respiratory or gastrointestinal infections like the common cold in humans; however, an adenovirus infection can be serious in persons with a compromised immune system or pre-existing respiratory or cardiac issues.130

Several characteristics are considered as advantages to using an adenoviral vector for delivering a vaccine antigen, including the ability to stimulate both an innate (cell-mediated) and humoral (adaptive) immune system response and because adenoviral vectored vaccines are easy to genetically manipulate. Another feature is that the adenovirus itself can trigger the vaccine’s inflammatory immune response. This means that it is not necessary to add an adjuvant to the vaccine to provoke an inflammatory response to stimulates immunity.131

Each 0.5 mL dose of the vaccine also contains citric acid monohydrate (0.14 mg), ethanol (2.04 mg), trisodium citrate dihydrate (2.02 mg), 2-hydroxypropyl-β-cyclodextrin (HBCD) (25.50 mg), polysorbate-80 (0.16 mg), and sodium chloride (2.19 mg). Additionally, each dose may also contain residual amounts of host cell DNA host and/or cell proteins. This vaccine does not contain a preservative and the vaccine vial stoppers are free of latex. The vaccine is approved to be administered as a single 0.5mL dose intramuscularly.132

In clinical trials, the vaccine was 66.9 percent effective in preventing moderate to severe COVID-19 occurring at least 14 days after vaccination and 66.1 percent effective in preventing moderate to severe COVID-19 occurring at least 28 days after vaccination.133 The vaccine, however, was reported to be only 42 percent effective in persons over the age of 60 who have underlying health conditions.134

On April 13, 2021, the FDA and CDC paused use of the Janssen/Johnson & Johnson vaccine after serious blood clots were reported in women between the ages of 18 and 49.135 By April 23, 2021, 15 cases and 3 deaths had been associated with the rare blood clot disorder, now referred to by health officials as thrombosis with thrombocytopenia syndrome (TTS). All cases were reported in women, with 2 occurring in women over 50 years of age. The CDC’s Advisory Committee on Immunization Practices (ACIP) voted to resume full use of the vaccine in all persons 18 years of age and older on April 23, 2021, by a vote of 10 to 4 (with one voting member abstaining due to a conflict of interest). Those who voted against the recommendation expressed concern regarding the lack of warning on the risk of TTS in women under 50 years of age.136 137

By May 7, 2021, there had been 28 cases of TTS and 3 deaths confirmed by the CDC to be related to the Johnson & Johnson/Janssen COVID-19 vaccine. Additionally, TTS has been reported in men and in women between 50 and 60, in addition to women between 18 and 49 years.138 As of April 7, 2022, 60 cases of TTS and nine associated deaths following the Janssen/Johnson & Johnson COVID-19 vaccine had been confirmed by the CDC and FDA.139 According to the CDC, TTS occurs at a rate of 1 case per 250,000 doses.140

On July 13, 2021, Janssen/Johnson & Johnson company officials reported that they were working on modifying their COVID-19 vaccine in an attempt to reduce or eliminate the risk of blood clots.141

Additionally, on July 13, 2021, the FDA announced revisions to the Fact Sheet for Healthcare Providers Administering the Johnson & Johnson/Janssen COVID-19 vaccine and the Fact Sheet for Recipients and Caregivers to include information regarding an increased risk of Guillain-Barré Syndrome (GBS) following vaccination. GBS, a serious neurological disorder where the body’s immune system attacks the peripheral nervous system, can cause muscle weakness, paralysis, and even death. According to the press release, the FDA reported 100 cases of GBS following vaccination, with 95 considered serious and requiring hospitalization, and one death. Government health officials noted that there was insufficient evidence to establish a causal relationship between the Johnson & Johnson/Janssen COVID-19 vaccine and GBS, and reported that “the known and potential benefits clearly outweigh the known and potential risks.”142

As of April 7, 2022, 313 cases of GBS following the Janssen/Johnson & Johnson COVID-19 vaccine had been identified in the VAERS data. According to the CDC, most cases occurred within two weeks of vaccination and among men, primarily those aged 50 and older.143

On December 16, 2021, the CDC gave a preferential recommendation for mRNA COVID-19 vaccines in lieu of the Johnson & Johnson/Janssen COVID-19 vaccine due to the risk of TTS.144 According to the CDC, use of the Johnson & Johnson/Janssen vaccine should be limited to persons who are unable to or unwilling to receive an mRNA COVID-19 vaccine, or when no other vaccine option is available.145 Limited safety and effectiveness data are available for use of a mix and match vaccine schedule.146

The FDA updated the Johnson & Johnson/Janssen COVID-19 Vaccine Fact Sheet for Health Care Providers Administrating Vaccine on January 11, 2022 with information regarding the serious risk of Immune Thrombocytopenia (ITP) within 42 days of vaccination. ITP is a blood disorder that can cause excessive bruising and bleeding due to very low levels of platelets.147

Janssen/Johnson & Johnson COVID-19 Booster Doses

Prior to August 31, 2022, health officials recommended that all persons who received a single dose of the Johnson & Johnson/Janssen COVID-19 get a first booster dose of COVID-19 vaccine at least two months after receipt of the first vaccine dose, and a second booster dose at least four months following the first booster dose. A dose of mRNA COVID-19 vaccine was recommended over the Johnson & Johnson/Janssen COVID-19 vaccine.148

As of August 31, 2022, a single booster dose of a bivalent mRNA COVID-19 vaccine is authorized for all persons who received a primary series of Janssen/Johnson & Johnson COVID-19. This vaccine is recommended to be administered at least two months following receipt of primary series or booster dose.149

 

Novavax COVID-19 Vaccine

On July 13, 2022, the FDA issued an EUA to Novavax for its adjuvanted COVID-19 vaccine, for use in adults 18 years and older who have not received a prior dose of COVID-19. The vaccine is authorized as a two-dose primary series, to be administered intramuscularly three weeks apart. 150 The EUA was expanded on August 19, 2022 to include adolescents 12 through 17 years.151

Maryland-based Novavax Inc, a biotechnology company which had never successfully delivered a product to market,152  developed an experimental vaccine using recombinant nanoparticle technology. Referred to as a protein subunit vaccine,153 NVX‑CoV2373 contains Novavax’s patented saponin-based Matrix-M™ adjuvant designed to enhance the immune response and stimulate high levels of neutralizing antibodies.154

Matrix-M1 contains nm (nanometers) of nanoparticles composed of Quillaja saponins, phospholipid and cholesterol. Quillaja saponins are chemical compounds extracted from the soapbox tree and are used as emulsifiers in food additives and beverages.155

According to the fact sheet for health care providers administering Novavax COVID-19 vaccine, the vaccine is supplied as a multi-dose vial containing 10 doses of 0.5mL. After the vial is punctured, it must be stored between 36 and 77 degrees Farhenheit and discarded after six hours.156

Each 0.5 mL dose of the Adjuvanted Novavax COVID-19 Vaccine contains 5 mcg of SARS-CoV-2 recombinant spike protein and 50 mcg Matrix-M adjuvant. The Matrix-M adjuvant is made of Fraction-A (42.5 mcg) and Fraction-C (7.5 mcg) of saponin extracts from the soapbark tree (Quillaja saponaria Molina). The recombinant spike protein is made by recombinant DNA technology in an insect cell line that is derived from cells of the Spodoptera frugiperda species.157  

Each dose of the Adjuvanted Novavax COVID-19 Vaccine also contains the following ingredients: potassium dihydrogen phosphate (3.85 mcg), potassium chloride (2.25 mcg), disodium hydrogen phosphate dihydrate (14.7 mcg), disodium hydrogen phosphate heptahydrate (2.465 mg), cholesterol, phosphatidylcholine, sodium dihydrogen phosphate monohydrate (0.445 mg), sodium chloride (8.766 mg) and polysorbate 80 (0.050 mg), and Water for Injection. The pH is adjusted with either sodium hydroxide or hydrochloric acid. Each 0.5 mL dose of the Novavax vaccine may also contain residual amounts of baculovirus and Sf9 cell proteins (≤ 0.96 mcg), lentil lectin (< 0.025 mcg), methyl-α-D-mannopyranoside (2 mcg), baculovirus and cellular DNA (≤ 0.00016 mcg), Triton X-100 (< 0.025 mcg), simethicone (< 2.19 mcg), and Tergitol (NP9) (< 0.05 mcg). The Adjuvanted Novavax COVID-19 Vaccine does not contain preservative and the vial stoppers are not made with natural rubber latex.158

In June 2022, the FDA’s Vaccine and Related Biologics Products Advisory Committee (VRBPAC) voted to recommend issuing Novavax an EUA for its COVID-19 vaccine for adults. VRBPAC made this recommendation despite the risks of myocarditis and pericarditis associated with the vaccine, as well as a lack of data on the effectiveness of the vaccine against the currently circulating Omicron COVID-19 strain. The FDA stated that the issuance of EUA would depend on an evaluation of Novavax’s manufacturing process. On June 3, 2022, Novavax notified the FDA of a change to the manufacturing process of its COVID-19 vaccine.159

On July 19, 2022, the CDC’s ACIP approved use of Novavax as a primary series for use in persons 18 years and older.160 As of September 2, 2022, booster doses of Novavax COVID-19 vaccine have not been authorized for individuals who received a primary series.161

 

 

Additional COVID-19 Vaccines

Although several COVID-19 vaccine candidates employ unproven vaccine technologies, many COVID-19 vaccines that employ traditional vaccine manufacturing methods are under development and in pre-licensure clinical trials.162 These include several experimental inactivated vaccine candidates by Chinese based pharmaceutical companies.163 164

Globally, over 360 COVID-19 vaccines are under development and as of August 30, 2022, 170 experimental vaccines were in clinical trials.165

AstraZeneca-University of Oxford Viral Vector COVID-19 vaccine
A development team from the University of Oxford in the United Kingdom endeavored to make an experimental COVID-19 vaccine candidate by the end of the summer of 2020. Teaming with AstraZeneca in April of 2020 to develop, manufacture, and distribute the ChAdOx1 nCoV-19 vaccine (now referred to as AZD1222) in the U.S., this COVID-19 vaccine candidate is a non-replicating viral vector vaccine that uses a chimpanzee adenovirus to express the SARS-CoV-2 protein.166 According to the University of Oxford:

“Genetic material has been added to the ChAdOx1 construct, that is used to make proteins from the COVID-19 virus (SARS-CoV-2) called Spike glycoprotein (S). This protein is usually found on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of the SARS-CoV-2 virus. The SARS-CoV-2 coronavirus uses its spike protein to bind to ACE2 receptors on human cells to gain entry to the cells and cause an infection.”167

The University of Oxford reported that the initial clinical trials of ChAdOx1 nCoV-19 would involve 800 individuals. Half would receive the experimental vaccine while the other half would serve as the control group and receive a meningitis vaccine (MenACWY).168

In July 2020, preliminary results of the AstraZeneca’s Phase 1 and Phase 2 trials were published in The Lancet.169 This study involved 1,077 healthy adults between 18 and 55 years of age who were randomly given either the ChAdOx1 nCoV-19 vaccine (AZD1222) or the meningococcal conjugate (MenACWY) vaccine. Systemic and local reactions were more common in the trial group given the experimental COVID-19 vaccine, and a selection of participants from both groups received prophylactic paracetamol (acetaminophen) before vaccinations were administered.

Headache and fatigue were the most commonly reported systemic reactions. Headaches were reported in the experimental COVID-19 vaccine group by 68 percent of the participants without acetaminophen and 61 percent with acetaminophen and in the MenACWY group by 41 percent of the participants without acetaminophen and 37 percent of the participants with acetaminophen. Fatigue was reported in the experimental COVID-19 vaccine group by 70 percent of the participants, who were not give acetaminophen prior to vaccination, and in the MenACWY group by 48 percent of the participants without acetaminophen. 

Other common systemic adverse reactions reported in the experimental COVID-19 vaccine group included feeling feverish (51 percent), chills (56 percent), muscle ache (60 percent)  and malaise (61 percent). Eighteen percent of participants who did not receive acetaminophen and 16 percent of participants who did reported a temperature of at least 100.4°F. Two percent of patients without acetaminophen reported a temperature of at least 102.2°F. In comparison, less than one percent of individuals receiving MenACWY reported a fever of at least 100.4°F, none of whom were receiving prophylactic acetaminophen. The intensity and severity of systemic and local reactions was highest on the first day after vaccination.170

Phase 3 clinical trials began in late August 2020. Their goal was to enroll 30,000 vaccine participants through 62 sites. On September 8, 2020, the pharmaceutical company announced that it was putting the trial on hold after a female participant in the U.K. developed transverse myelitis, a rare but serious neurological disorder, which causes inflammation of the spinal cord.171

This was the second time that AZD1222 vaccine trials were placed on hold. In July 2020, trials were paused after a woman developed multiple sclerosis; however, company officials reported that her diagnosis was not related to vaccination.172

While clinical trials resumed quickly in several countries including Great Britain, Japan, South Africa, India,173 and Canada, 174 trials in the U.S. remained on hold until October 23, 2020. 175

On October 1, 2020, the European Medicines Agency (EMA) stated that it had started reviewing AstraZeneca’s COVID-19 clinical trial data in real time, and anticipated that following approval, all adults in Britain could receive at least one vaccine dose within 6 months.176

Trials in the U.S. involving the University of Oxford and AstraZeneca’s experimental COVID-19 vaccine candidate were put on hold in early September 2020 due to safety concerns. While several countries including Canada, Japan, Brazil, South Africa, and Great Britain continued with clinical trials despite these concerns,177 U.S trials did not resume until October 23, 2020. According to the Wall Street Journal, the FDA did not fault the vaccine for the serious neurological events that occurred in two trial participants, however, they have not yet ruled out a link.178

At the January 27, 2021 ACIP meeting, company officials from AstraZeneca reported that across the four studies, serious adverse events occurred in 168 participants, with 79 occurring among persons who received the experimental COVID-19 vaccine, and 89 among persons who received either the MenACWY vaccine or saline control. In total, 175 serious adverse events were reported; however, only four events were considered as possibly related to vaccination by clinical trial investigators. In the COVID-19 vaccine group, one participant experienced a high fever two days following the first vaccine dose that resolved with paracetamol (acetaminophen) treatment on the same day and another participant developed transverse myelitis two weeks after the second vaccine dose. In the control group, one participant developed autoimmune hemolytic anemia ten days after MenACWY, and another participant developed transverse myelitis two months after the first control dose.179

AstraZeneca company officials reported that most solicited adverse events were mild to moderate and the majority resolved within a few days of vaccination. The most commonly reported adverse events included injection site tenderness, injection site pain, fatigue, headache, muscle and joint pain, malaise, fever, chills, and nausea. Adverse events were more common after the first vaccine dose. 180

On January 29, 2021, the European Union approved the vaccine for use in individuals 18 years and older despite limited data to support its effectiveness in adults over the age 55 years. The University of Oxford and AstraZeneca’s experimental COVID-19 vaccine is estimated to have an efficacy of about 60 percent.181 Health officials in Germany, however, did not recommend use of the vaccine in adults 65 years of age and older after concluding that there was not enough data to determine whether the vaccine was effective in this population.182

Health officials in South Africa halted use of the AstraZeneca COVID-19 vaccine in February 2021, after it was found to be less than 25 percent effective against the B.1.351 (Beta) variant, which was the most common SARS-CoV-2 virus variant circulating in South Africa at the time.183

On March 12, 2021, CNN reported that while AstraZeneca, and UK and European regulators stated there was no evidence of this experimental COVID-19 vaccine causing blood clots, a number of countries had already suspended use of the vaccine. These countries included Denmark, Norway, Iceland, and Thailand. Other countries, like Austria and Italy chose instead to suspend specific batches of the vaccine, while Spain delayed rollout of the AstraZeneca vaccine.184 On June 11, 2021, Italy suspended use of the vaccine in persons under 60 years following the death of an 18-year-old female from cerebral hemorrhage 16 days post vaccination.185

The World Health Organization (WHO) issued a statement on March 19, 2021 stating that their Global Advisory Committee on Vaccine Safety had reviewed the data on the vaccine in relation to blood clots and low platelets after vaccination and concluded that the rates of these events are fewer than when they occur naturally in the generalized population. The WHO added and that these events would continue to be monitored.186

Soon thereafter, Canadian health officials joined France and limited the vaccine’s use in persons under 55 years of age, stating “From what is known at this time, there is substantial uncertainty about the benefit of providing AstraZeneca COVID-19 vaccine to adults under 55 years of age,” and had requested a new risk analysis on the vaccine’s risks and benefits broken down by age and gender.187 On March 30, 2021, Germany limited its use to persons over the age of 60.188

On April 7, 2021, the European Medicines Agency (EMA) safety committee (PRAC) concluded that “unusual blood clots with low blood platelets should be listed as very rare side effects of Vaxzevria (formerly COVID-19 Vaccine AstraZeneca).” In their report, PRAC reminded health care professionals and vaccine recipients to be aware of the possibility of “blood clots combined with low levels of blood platelets occurring within 2 weeks of vaccination.” PRAC reports that the blood clots occurred in the abdomen (splanchnic vein thrombosis), brain (cerebral venous sinus thrombosis or CVST), and arteries, in conjunction with low levels of blood platelets and at times with bleeding.189

According to PRAC, “One plausible explanation for the combination of blood clots and low blood platelets is an immune response, leading to a condition similar to one seen sometimes in patients treated with heparin (heparin induced thrombocytopenia, HIT).” New studies and revised protocols to ongoing clinical trials have been requested by safety officials.190

An in-depth review of 24 cases of splanchnic vein thrombosis and 62 cases of cerebral venous sinus thrombosis reported to the EU drug safety database, EudraVigilance, as of March 22, 2021 was completed by the committee. Of these cases, 18 were reported as fatal. The committee, however, continued to recommend the vaccine, stating that “The reported combination of blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.”191

Vaccine use has resumed in many countries; however, some countries have restricted use of the product to persons over the age of 60 or 65 years of age. As of April 19, 2021, the vaccine remained suspended in Cameroon, Norway, and Denmark.192 On April 14, 2021, Danish health officials announced that it was halting use of the vaccine after studies had noted that blood clots occurred at a rate of one in 40,000 people.193

On July 13, 2021, AstraZeneca company officials reported that they were working on modifying their COVID-19 vaccine in an attempt to reduce or eliminate the risk of blood clots.194

The AstraZeneca COVID-19 vaccine has also been linked to Guillain-Barré Syndrome (GBS). GBS, a serious neurological disorder where the body’s immune system attacks the peripheral nervous system, can cause muscle weakness, paralysis, and even death. On September 8, 2021, the EMA stated that GBS should be listed as a potential adverse event following vaccination. According to the EMA, as of July 31, 2021, 833 cases of GBS had been reported after AstraZeneca COVID-19 vaccination.195

Inovio Pharmaceuticals INO-4800 DNA Vaccine

Gene-based vaccines, which include DNA and mRNA types, encode for a specific viral protein from a pathogen - such as the spike protein for the SARS-CoV-2 virus. DNA vaccines deliver pieces of DNA into the nucleus of human cells in ways that result in production of pathogen protein antigens that subsequently, stimulate the immune system to produce antibodies specific to the pathogen’s antigen without becoming infected by the pathogen that can cause the disease. Compared to traditional vaccines, nucleic acid (genetic) vaccines are less inexpensive and easier to manufacture because they consist only of DNA or RNA, which is taken up and translated into protein by host cells.196

In early April 2020, Inovio pharmaceuticals began Phase 1 clinical trials of its experimental COVID-19 DNA vaccine, INO-4800. Inovio’s COVID-19 vaccine research has been funded by a $9 million grant from the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) and a $5 million grant from the Bill and Melinda Gates Foundation. It also had a partnership with Philadelphia’s Wistar Institute and Beijing Advaccine Biotechnology Co. in China to develop the vaccine in addition to a $11.9 million contract with the U.S. Department of Defense to provide the experimental DNA coronavirus vaccine for potential military use.197

Inovio’s INO-4800 vaccine injects a small piece of circular DNA, called a plasmid (pGX9501), that encodes for the entire length of the Spike glycoprotein of SARS-CoV-2198  to provoke the vaccine recipient’s cells into producing antibodies. The biggest challenge for DNA/RNA vaccines is getting patients’ cells to accept the introduced genetic material. At this point, the most effective technique appears to be electroporation, which is the delivering of short pulses of electrical current to the patient to open cell pores and allow the plasmids to enter. This vaccine, unlike many of its counterparts, is stable at room temperature for over a year. 199 200

On June 30, 2020, Inovio Pharmaceutical announced positive results from its Phase 1 clinical trials. In the initial trial, 40 healthy adults between 18 and 50 years of age were administered two vaccine doses four weeks apart. Participants received either a 1.0mg or 2.0mg dose administered using INOVIO's CELLECTRA® 2000 device – a device that delivers short pulses of electrical current to the patient in addition to the vaccine. The electricity creates temporary pores in a patient’s cell membranes and this process enables the DNA/RNA to enter.201 202

According to company officials, all 10 reported adverse events were considered Grade 1 and involved localized injection site redness.203

The World Health Organization (WHO) has acknowledged that gaps in scientific knowledge exists regarding DNA vaccines and that their immune responses are not fully understood.204

Some of the outstanding questions about DNA vaccine safety include:205

  • chronic inflammation because the vaccine continually stimulates the immune system to produce antibodies;
  • possible integration of plasmid DNA into the body’s host genome resulting in mutations;
  • problems with DNA replication;
  • triggering of autoimmune responses, and
  • activation of cancer-causing genes.

INOVIO’s CELLECTRA® 2000 electroporation device is also associated with higher rates of injection site pain in comparison to standard injections. A small clinical trial that involved the injection of a sterile solution followed by the use of the CELLECTRA® 2000 device reported mild to moderate injection pain, tenderness, redness and swelling, involuntary muscle contractions and increases in serum creatine phosphokinase (CK). CK is an enzyme found in the brain, heart, skeletal muscle, and other tissues and an increase in levels is indicative of muscle damage in the body.206

In late September 2020, the U.S. Food and Drug Administration (FDA) placed the INO-4800 experimental vaccine trials on partial hold and requested more information on the clinical trials and the device used to deliver the vaccine.207 While the Phase 3 clinical trials remained on hold, the FDA permitted the compnay to proceed with Phase 2 clinical trials. According to INOVIO:208

“The Phase 2 segment of the trial is designed to evaluate safety, tolerability and immunogenicity of INO-4800 in a 2-dose regimen (1.0 mg or 2.0 mg), in a three-to-one randomization to receive either INO-4800 or placebo for each dose to confirm the more appropriate dose(s) for each of three age groups with high risks of infection (18-50 years, 51-64 years and 65 years and older) for the subsequent Phase 3 efficacy evaluation. The Phase 3 segment of the INNOVATE trial remains on partial clinical hold until INOVIO satisfactorily resolves the FDA's remaining questions related to the CELLECTRA® 2000 device that will be used to deliver INO-4800 directly into the skin. The company plans to resolve the remaining device questions during the conduct of Phase 2 segment and prior to the start of the Phase 3 segment of the trial.”

In early November 2021, Inovio company officials announced that the FDA had lifted its partial hold on the U.S. late stage clinical trial.209

 

What is the history of COVID-19 vaccine use in America?

vaccine history

Immediately after the January 30, 2020 WHO declaration that a novel coronavirus (SARS-CoV-2) outbreak in China posed a “public health emergency of international concern,” the Gates Foundation  and World Health Organization (WHO)  issued press releases informing the world that experimental coronavirus vaccines already in development would be put on a fast track to licensure for global use.

A research and development plan published by WHO stated there was an “urgent need” to fill in scientific knowledge gaps about the “basic biology” of COVID-19 illness and clinical evolution of COVID-19 and its epidemiology, as well as the need to develop appropriate animal models for research because some previous SARS and MERS vaccine studies in animals showed enhanced respiratory disease can occur in vaccinated animals after exposure to the live virus. 

 

Vaccine Development Hampered by Enhanced Respiratory Disease

For the past two decades, coronavirus vaccine research has been hampered by one consistent vaccine adverse outcome in particular - paradoxical immune enhancement or disease enhancement. This outcome has not only been observed in SARS-CoV-1 and MERS-CoV vaccines, but also with vaccines using formalin-inactivation for measles (this vaccine was withdrawn in 1967) and respiratory syncytial virus (RSV) vaccines. Disease enhancement has also been observed with the live tetravalent dengue vaccine, Dengvaxia.   

Vaccine induced disease enhancement occurs when the vaccine primes detrimental T cell response or antibodies in the recipient and increases the risk for infection or severe disease. This means that a vaccinated person may seem fine until they contract the illness, but the excess non-neutralizing antibodies not only fail to protect the person from infection but actually make it easier for the virus to infect cells and cause damage and, as a result, the disease is much more severe than it would have otherwise been.   

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COVID-19 Vaccine Development Efforts

By mid-March and early April 2020, the WHO, National Institutes of Health  universities,  and global pharmaceutical corporations  had announced development of more than 50 experimental COVID-19 vaccines.   

Responding to the call by public health officials to lockdown the U.S. with in-home quarantines, Congress passed the CARES Act signed into law on March 27, 2020 that would cost American taxpayers over two trillion dollars. This federal legislation included $27 billion for development of COVID-19 vaccines, drug therapies and purchase of pandemic medical supplies. The legislation, however, did not include a cap placed on how much money drug companies could charge and profits they could make on the COVID-19 vaccines and drug therapies they develop with the use of money from the government. 

On March 30, 2020, the HHS Assistant Secretary of Preparedness and Response announced that the government was taking steps to “speed the development and manufacturing of vaccines to prevent COVID-19.”  

The Biomedical Advanced Research and Development Authority (BARDA) was created by Congress in 2006 under the Pandemic and All Hazards Preparedness Act,  legislation that has given billions of dollars to DHHS since then to develop “bioterrorism” and pandemic influenza vaccines.  That federal legislation also removed all civil liability from pharmaceutical companies for injuries and deaths caused by vaccines and drugs manufactured in response to declared public health emergencies, such as pandemics. 

Johnson & Johnson issued a press release on March 30, 2020, stating that BARDA had awarded Janssen Pharmaceutical Companies $1 billion to establish new U.S. vaccine manufacturing capabilities and additional production capacity outside the U.S to produce a global supply of more than 1 billion doses of the COVID-19 vaccine. 

According to a March 30, 2020 Reuters report, Moderna, Inc. “also signed a deal with the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services. The arrangements were part of the federal government’s effort to encourage drugmakers to be able to produce massive amounts of COVID-19 vaccines even before any are proven to work.” 

In May 2020, former President Donald Trump formally announced the framework and leadership of “Operation Warp Speed”, a private-public partnership aimed at making a COVID-19 vaccine available to the public by January of 2021. Trump appointed venture capitalist and former Chairman of Global Research and Development and Chairman of Global Vaccines at GlaxoSmithKline Dr. Moncef Slaoui as chief advisor on vaccine development. General Gustave F. Perna, the U.S. army’s four-star general responsible for global supply chain and materiel and installation readiness for the U.S. Army, was selected as chief operating officer and charged with COVID-19 vaccine distribution. 

"President Trump's vision for a vaccine by January 2021 will be one of the greatest scientific and humanitarian accomplishments in history, and this is the team that can get it done," said HHS Secretary Alex Azar. "Dr. Slaoui and General Perna are ideal leaders for this unprecedented effort to get vaccines, therapeutics, and diagnostics to American patients much faster than ever before. Since January, America's scientists and innovators have been working day and night on this national effort. President Trump has refused to accept business-as-usual timelines for vaccines and other essential tools, and instead has insisted that America, and the world, needs answers faster. Under the President's leadership, his administration and American industry will squeeze every last inefficiency out of the process and pour every resource we can into this effort."

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U.S. Food and Drug Administration Vaccine Approval process

On June 30, 2020, the U.S. Food and Drug Administration (FDA) announced that a COVID-19 vaccine would only receive approval if it were at least 50 percent more effective than a placebo at either preventing infection or reducing illness severity. 

The FDA released its guidance for industry regarding EUA approval for COVID-19 vaccines on October 6, 2020, and stated that they would be requiring that at least half of all Phase 3 clinical trial participants be followed for at least two months following administration of the second vaccine dose. The FDA also requested that vaccine makers submit information on a minimum of five cases of severe COVID-19 disease among individuals who received the placebo. 

Under EUA authority, the FDA Commissioner may permit “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN (CBRN = chemical, biological, radiological, nuclear) threat agents when there are no adequate, approved, and available alternatives.” 

On October 22, 2020, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) met to discuss COVID-19 vaccine safety and efficacy, and included groups representing ethnic and racial minorities.  VRBPAC is comprised of non-FDA “experts” whose charge is to provide “advice to the Agency regarding the safety and efficacy of the vaccine for the proposed indication.” 

Safety concerns dominated much of the meeting and several committee members expressed worry that the median two-month safety monitoring period appeared to be “arbitrary”. Additionally, if EUA approval was granted, there was concern that placebo control groups and blinding of the Phase 3 trials would be halted immediately and  additional vital data would be lost. 

A presentation on vaccine hesitancy by the Reagan-Udall Foundation for the Food and Drug Administration, a nonprofit established by Congress to advance the FDA’s overall mission, reported on the public’s concern over the speed of vaccine development and their overall distrust of the healthcare system and of government. Several committee members stated that allowing a COVID-19 vaccine to be approved under EUA would only increase vaccine safety concerns. 

Concerns that minority populations were under-represented in clinical trials were discussed, however, Dr. Doran Fink of the FDA's Office of Vaccines Research and Review stated that while under-representation was not ideal, this would not cause the vaccine to be restricted for use in this demographic.  Vaccine hesitancy among racial and ethnic minorities was also highlighted and attributed to past historical experiments that have resulted in mistrust of government and health officials. 

COVID-19 vaccine efficacy discussions included a presentation by Dr. Hilary Marston, of the National Institutes of Health, who recommended that the FDA require at least a 60 percent efficacy rate for any approved COVID-19 vaccine. 

Several committee members expressed concern that the FDA had allowed vaccine manufacturers to use broad definitions of COVID-19 disease as their primary endpoint criteria. Concerns included the potential that a vaccine that showed protection against mild disease could be licensed even though the product did not reduce hospitalizations or deaths. 

VRBPAC Committee members also did not unanimously support the idea of allowing data from adult vaccine trials to be used to measure vaccine efficacy for children.   VRBPAC Chair, Dr. Arnold Monto cautioned that due to differing immune responses and the potential risk of Multisystem Inflammatory Syndrome in Children (MIS-C), standard bridging of data may be inappropriate. 

Additional VRBPAC meetings for each vaccine candidate approval or EUA was promised by the FDA, however, the FDA is not required to follow any recommendations made by their federal committee. 

Despite previously stating that they were committed to use an advisory committee composed of independent experts to ensure deliberations about authorization or licensure are transparent for the public  the FDA declined to hold a VRBPAC meeting prior to granting a license to BioNTech for its mRNA COVID-19 vaccine. In the Summary Basis for Regulatory Action Document published to support approval of Comirnaty, the Pfizer-BioNTech mRNA COVID-19 vaccine, the FDA reported that it “did not refer this application to the VRBPAC because our review of the information submitted to this BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.” 

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Gene-Based Vaccines and Traditional Vaccines

Drug companies and government agencies racing to be the first to license a COVID-19 vaccine, began using different technology platforms to create experimental vaccines: inactivated virus, attenuated virus, recombinant protein subunit, virus-like particle, DNA, RNA and replicating and non-replicating viral vector.  Traditional viral vaccines contain attenuated or inactivated viruses or protein subunits in addition to adjuvants, such as aluminum, to stimulate an immune response that produces artificial immunity. For the past two decades, researchers have been experimenting with new technology platforms, notably ones that introduce foreign DNA and RNA directly into the body’s cells for the purpose of developing experimental vaccines for SARS, MERS, HIV and other diseases.    

Gene-based vaccines, which include DNA and mRNA types, encode for a specific viral protein from a pathogen - such as the spike protein for the SARS-CoV-2 virus. The genetic encoding instructs cells in the vaccine recipient to produce antigens that stimulate the immune system to produce antibodies specific to the antigen, without the recipient becoming infected by the pathogen that causes the disease. Compared to traditional vaccines, nucleic acid (genetic) vaccines are inexpensive and easier to manufacture because they consist only of DNA or RNA, which is taken up and translated into protein by host cells.   

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COVID-19 mRNA Vaccine Development

Messenger RNA (mRNA) vaccines inject human cells with mRNA, usually within lipid nanoparticles, to stimulate cells in the body to become manufacturers of viral proteins.    In March 2020, a virologist at Imperial College London told Chemistry World that one advantage of using mRNA technology to make vaccines for humans is that, “Rather than generating proteins in a manufacturing plant and purifying them, you are getting the muscle to do the job and make the protein itself.” 

While traditional vaccines typically work with a person’s acquired immune system (immunity gained from exposure to pathogens), COVID-19 mRNA vaccines also have the potential to trigger an immune response from a person’s innate immune system, or the immunity we are born with. However, there are many unknowns, such as length of immunity provided by COVID-19 mRNA vaccines, whether or not the correct viral proteins have been chosen, and the frequency and severity of vaccine reactions and disease enhancement. 

Moderna COVID-19 Vaccine

The National Institute of Allergy and Infectious Diseases (NIAID) headed by Dr. Anthony Fauci issued a press release on March 16, 2020 announcing that a Phase 1 human clinical trial conducted by Kaiser Permanente Washington Health Research Institute in Seattle had begun to evaluate an experimental mRNA vaccine for COVID-19 (mRNA-1273) co-developed by NIAID scientists and scientists at Moderna, Inc, based in Cambridge, Massachusetts. The Coalition for Epidemic Preparedness (CEPI) helped fund the manufacturing of the vaccine for the Phase 1 clinical trial. 

Moderna and NIAID began conducting human trials of the experimental mRNA-1273 COVID-19 vaccine prior to first conducting pre-clinical animal trials, which has been an important and customary part of vaccine development and testing process.  On March 30, 2020, Moderna stated that its COVID-19 vaccine might be ready for emergency use in certain individuals, including healthcare workers, by the fall of 2020.

“The Company further reported that while a commercially-available vaccine is not likely to be available for at least 12-18 months, it is possible that under emergency use, a vaccine could be available to some people, possibly including healthcare professionals, in the fall of 2020. Any emergency use would be subject to authorization by the appropriate regulatory agencies, based on the emergence of clinical data for mRNA-1273 that would support use of the vaccine prior to licensure.”  

Although neither DNA or mRNA vaccines had been tested in large-scale clinical trials, an April 3, 2020 article in Chemical and Engineering News highlighted the breakneck speed at which COVID-19 vaccines “are moving new technologies from the computer and into the clinic at an unprecedented rate.” What should be separate pre-licensure phases for proving safety and effectiveness - preclinical animal models, clinical testing, and manufacturing – were now “happening all at once.” 

Moderna announced on May 18, 2020, that Phase 1 human clinical trials of its experimental COVID-19 vaccine showed positive results, with eight of the 45 healthy adult volunteer trial subjects developing antibodies that may provide protection against the SARS-CoV-2 virus. 

The company also reported that four participants suffered Grade 3 vaccine reactions. Of the four participants who experienced Grade 3 reactions, three had received the 250-µg dose level and one had received the 100-µg dose level. The U.S. Department of Health and Human Services (HHS) describes a Grade 3 adverse event as

“severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care” such as “bathing, dressing and undressing, feeding self, using the toilet, taking medications.” 

On July 27, 2020, National Institute of Allergy and Infectious Diseases (NIAID) announced that Phase 3 clinical trials of the Moderna COVID-19 vaccine had begun. The vaccine, a joint venture between Moderna, Inc., and the NIAID, part of the National Institutes of Health (NIH), was expected to enroll 30,000 healthy COVID-19-negative adults at 89 clinical test sites. 

According to NIAID, study participants would be randomly assigned 1:1 to receive either two doses of the 100- µg experimental mRNA COVID-19 vaccine or two normal saline placebo doses. NIAID officials reported that the study’s primary goal was to evaluate vaccine safety and whether two vaccine doses could prevent symptoms of COVID-19. Additional secondary goals included evaluation of the vaccine’s ability to prevent severe COVID-19 disease or death, and the effectiveness of a single vaccine dose in preventing symptomatic COVID-19. 

Moderna COVID-19 Vaccine EUA

In the U.S., Moderna’s mRNA COVID-19 vaccine Phase 3 clinical trials initially stalled due to the inability by company officials to recruit enough minority volunteers – a requirement of the FDA for any vaccine maker seeking Emergency Use Authorization (EUA) for its product. Health officials blamed past unethical and immoral medical experiments that targeted minority populations and not employing people of color to recruit minority clinical trial volunteers.  However, on October 22, 2020, Moderna reported that it had completed enrollment of trial participants and had recruited 11,000 participants from ethnically diverse communities  and participants between 18 and 65 years of age with underlying conditions. 

On November 16, 2020, Moderna announced, that its experimental mRNA vaccine candidate showed a 94.5 percent efficacy against COVID-19. Company officials reported that their first interim results found a total of 95 COVID-19 cases among trial participants, with 90 cases in the placebo group and five in the vaccine group. According to Moderna, no severe cases of COVID-19 occurred among the vaccine recipients while 11 severe cases occurred in the placebo cases. 

On December 18, 2020, the FDA issued an EUA for Moderna’s mRNA COVID-19 Vaccine for use in persons 18 years of age and older. 

Anaphylaxis following vaccination with Moderna’s COVID-19 vaccine were also reported within days of the EUA approval. According to a report published by the CDC, between December 21, 2020 and January 10, 2021, 108 adverse events reports were identified as possible cases of severe allergic reaction to the vaccine. However, health officials considered only 10 cases to be anaphylaxis and reported that anaphylaxis occurred at a rate of 2.5 cases per million doses of Moderna COVID-19 vaccine administered. 

Deaths following Moderna’s COVID-19 vaccination were also reported. On Jan. 5, 2021, baseball Hall of Famer Hank Aaron was administered the Moderna vaccine in an event that appeared to encourage others, especially African-Americans, to receive the vaccine. Seventeen days later, on January 22, 2021, Aaron died. Health officials have denied that the COVID-19 vaccine played a role in his death, and report that it was purely coincidental. 

According to the federal vaccine adverse event reporting system (VAERS), as of the October 8, 2021 CDC data release there were a total of 309,258 reports submitted to VAERS associated with the experimental Moderna COVID-19 vaccine. Noted within these reports were 4,144 deaths; 5,498 permanent disabilities; 19,514 hospitalizations, 28,865 emergency room visits; and 4,585 life threatening events. Of the deaths reported in CDC’s October 8, 2021 data release, over 71 percent of overall reported deaths occurred in persons 65 years of age and older. Click for the most recent information on reports submitted to VAERS.

In early April 2021, Moderna CEO Stéphane Bancel reported that a third vaccine dose would be needed within one year. In an interview with Business Insider, Bancel stated that "I hope this summer to get the vaccine authorized for a boost so that we can help people getting boosted before the fall, so that we all have a normal fall and not a fall and winter like we just saw in the last 6 months." Moderna officials have reported that the vaccine is 90 percent effective six months after the second vaccine dose. 

On July 8, 2021, the CDC and FDA announced that booster doses of COVID-19 vaccines were not required at this time and they, along with the National Institutes of Health (NIH), were actively engaged “in a science-based, rigorous process to consider whether or when a booster might be necessary.” 

One month later, however, the FDA authorized use of a third dose of the Moderna COVID-19 vaccine in persons with certain immunosuppressive conditions, such as solid organ transplant recipients and individuals with similar conditions. 

On August 18, 2021, Health and Human Services (HHS) announced a plan to begin administration of COVID-19 mRNA booster doses beginning the week of September 20, 2021. Public health officials recommended that the third dose be administered eight months following receipt of the second COVID-19 booster dose.  Leading health officials, however, have reported that review of the application to support the use of a third Moderna vaccine dose would likely not be completed prior to the White House’s September 20th timeline to begin administration of the additional dose. According to health officials, data submitted to the FDA as of September 1, 2021 was “found inadequate and needs strengthening.” 

In early May 2021, Moderna reported that the vaccine was 96 percent effective in adolescents between 12 and 17 years of age and that the company was planning to submit data for full FDA approval by the end of the month.  As of October 16, 2021, the vaccine is only authorized for use in persons 18 years of age and older. 

Moderna Vaccine Contamination Concerns

In late August 2021, Japanese health officials announced that it had suspended the use of 1.63 million Moderna mRNA vaccine doses after contaminants were noted in certain vials. These contaminants were reported to be stainless steel particles that were attributed to the manufacturing process. Company officials from Moderna along with representatives from Takeda Pharmaceuticals, the company that distributes the vaccine for use in Japan, reported that they did not believe that the stainless-steel contaminants would cause adverse health problems. Company officials reported that the particles were likely caused by friction between metal in the machinery used to place the stoppers on the vaccine vials. 

Three deaths following receipt of the contaminated vaccines have been reported by Japanese health officials as of September 7, 2021. The deaths, however, are currently considered coincidental and unrelated to vaccination. 

On September 7, 2021, Japan has stopped use of the Moderna vaccine and have announced plans to begin use of the Novavax COVID-19 vaccine.  

Profits from Moderna COVID-19 Vaccines

Profits from sales of the Moderna COVID-19 vaccine are expected to earn the company approximately $19.2 Billion dollars in 2021. 

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Pfizer-BioNTech COVID-19 Vaccine

Another experimental mRNA COVID-19 vaccine developed in a partnership between U.S. based pharmaceutical giant Pfizer, and German drug maker BioNTech, began human trials in late April 2020 in Germany. In early May 2020, Phase 1 and Phase 2 clinical U.S. trials evaluated the safety, tolerability, immunogenicity and potential efficacy of four different SARS-CoV-2 mRNA vaccine candidates using a two-dose or single-dose schedule, at up to three different dose levels and in three age groups (18 to 55 years old, 65 to 85 years old and 18 to 85 years old). 

Trial participants were expected to receive one of four vaccine candidates—BNT162a1, BNT162b1, BNT162b2, BNT162c2 or a placebo.  Each vaccine candidate represented a different mRNA formulation and target antigen. Albert Bourla, CEO of Pfizer, stated that if one or two variations of the vaccine candidates appeared successful, human trials would expand to include thousands of participants by September 2020. Additionally, Bourla stated:

“If things go well, and we feel that the product is safe and efficacious, and the FDA [Food and Drug Administration and EMA [European Medicines Agency and other regulatory agencies feel the same, we will be able to deliver millions of doses in the October time frame.” 

The Phase 1/2 trials involved 45 healthy adults between the ages of 18 and 55 years and over 50 percent of participants experienced adverse reactions. Two participants suffered severe reactions. A Grade 3 fever of over 101.3°F two days after vaccination was experienced by one adult and sleep disturbance one day after vaccination was experienced by another. 

On July 27, 2020, Pfizer and BioNTech announced the beginning of Phase 2/3 global trials (except China) of their BNT162b2 vaccine candidate. This experimental vaccine would be a 30µg level dose administered in a 2-dose regimen. Company officials reported that trials would include up to 30,000 adults between 18 and 85 years of age and if successful, they would pursue regulatory approval of some form by October 2020. If approved, their plan was to supply up to 100 million doses globally by the end of 2020, and 1.3 billion doses by the end of 2021. 

In mid-September, Pfizer and BioNTech reported that they had submitted an amended plan to the FDA to increase the number of trial participants to 44,000 and permit inclusion of individuals with chronic and stable Hepatitis B, Hepatitis C, and HIV as well as adolescents as young as 16 years of age.  They also reported that trial participants were reporting mild-to-moderate adverse reactions which included headache, fatigue, chills, and muscle pain. Fevers, including high fevers, were also reported. Pfizer’s head of vaccine research and development stated that the data was being monitored by an independent monitoring committee that "has access to unblinded data so they would notify us if they have any safety concerns and have not done so to date." 

Pfizer-BioNTech COVID-19 Vaccine EUA

On November 9, 2020, Pfizer-BioNTech issued a press release reporting that their experimental COVID-19 vaccine had an efficacy rate of over 90 percent “at 7 days after the second dose” in trial participants who had no prior history of SARS-CoV-2 infection.  Pfizer-BioNTech applied for Emergency Use Authorization (EUA) approval from the FDA on November 20, 2020  and received EUA approval on December 11, 2020 for use in persons 16 years of age and older. 

The experimental vaccine was previously granted EUA status in the U.K. on December 2, 2020  and within days of the vaccine’s initial roll-out, reports of anaphylaxis following vaccination began to surface. This prompted U.K. health officials to issue a warning against administration of the vaccine in persons with a previous history of anaphylaxis to any medicine or food. 

Immediately following the FDA issuance of an EUA for Pfizer-BioNTech’s COVID-19 vaccines, reports of anaphylaxis began to appear in the U.S. media. Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, suggested that a chemical ingredient called polyethylene glycol (PEG)—a polymer derived from petroleum used as an excipient (a diluting agent) in both the BNT162b2 vaccine and Moderna’s COVID-19 vaccine known as mRNA-1273, was likely responsible for the severe reactions. 

Between December 14 and 23, 2020, 21 cases of anaphylaxis were reported to the federal Vaccine Adverse Events Reporting System (VAERS), with 71 percent occurring within 15 minutes of vaccine administration. Of these cases, 17 reports were in persons with a past history of allergic reaction, including seven who had previously reported a history of anaphylaxis. Public health officials reported that anaphylaxis following Pfizer-BioNTech’s COVID-19 vaccine occurred at a rate of 11.1 cases per million doses administered. 

In addition to reports of anaphylaxis, deaths following Pfizer-BioNTech’s vaccine administration were also reported to VAERS. In January 2021, a 56-year-old obstetrician developed a bleeding disorder within 72 hours of vaccination, and died 16 days later of a stroke. 

As of the October 8, 2021 CDC release of data, reports submitted to VAERS for the Pfizer-BioNTech’s experimental COVID-19 vaccine for serious vaccine adverse events were 426,948. Noted within these reports were 11,350 deaths; 17,699 permanent disabilities; 54,335 hospitalizations; 52,875 emergency room visits; and 12,143 life threatening events. Of the reported deaths for this release of data, 50 percent of the deaths did not denote an age, with 40 percent occurring in persons 65 years of age and older. Click for the most recent information on reports submitted to VAERS.

In January 2021, health officials in Norway reported that they were investigating the deaths of 23 elderly individuals following vaccination with the Pfizer-BioNTech COVID-19 vaccine. The Norwegian Medicines Agency (NOMA) concluded that in 13 of the 23 deaths, common mRNA vaccine adverse reactions, such as diarrhea, fever, and nausea may have contributed to the deaths in the frail patients.  Deaths following the Pfizer-BioNTech COVID-19 vaccine were also reported in Israel,  Germany,  Portugal and Switzerland. 

In mid-December 2020, pharmacists administering the Pfizer-BioNTech COVID-19 vaccine discovered that vials contained six or even seven vaccine doses, instead of five – the amount listed on the product vial. The extra doses were attributed to overfill of the vials and dependent on the type of needle and syringe used to administer the vaccines.  In January 2021, the FDA officially granted Pfizer’s request to update the EUA Fact Sheet to clarify that each vial contained six doses.   

In order for all six vaccine doses to be extracted from the vial, special syringes known as low dead space syringes are required, which are in short supply. The lack of proper syringes caused controversy in Europe in January 2021 when it was revealed that Pfizer would be paid for six vaccine doses of the vaccine even though it was only possible to extract five doses from the vial. The U.S. government finalized a contract with Pfizer that would permit government officials to track which vaccine shipments came with dead space syringes and which did not. Shipments accompanied by dead space syringes would be counted as having six doses per vial, while those with regular syringes would count as having only five. 

On May 10, 2021, the FDA expanded the EUA granted Pfizer/BioNTech to distribute its experimental mRNA vaccine in the U.S. to include administration to children as young as 12 years old  and the CDC’s ACIP voted to approve its use in this population on May 12, 2021. 

The approval for use in adolescents 12 to 15 years was based on a small clinical trial involving 2,260 teens, of which 1,131 received the vaccine and 1,129 received a saline placebo.  According to the FDA’s Fact Sheet for Healthcare Providers Administering Vaccine: 

“In a clinical study, adverse reaction in adolescents 12 through 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%).”

During the clinical trial, nearly 11 percent of 12- to 15-year-olds experienced a severe or Grade 3 vaccine reaction, with one study participant experiencing a Grade 4 reaction of a fever of 40.4°C. Five adolescents who received the Pfizer vaccine experienced a serious adverse event (SAE) during the trial, however, none of these events were considered by clinical trial investigators to be related to vaccination. 

On July 16, 2021, the FDA announced that it had accepted the Biologics License Application (BLA) from Pfizer requesting full licensure and had granted a priority review of the application.   In early August 2021, the FDA announced that it was aiming to fully approve the Pfizer-BioNTech COVID-19 vaccine by Labor Day. 

Pfizer-BioNTech COVID-19 Vaccine Approval

On August 23, 2021 the FDA licensed and granted EUA status to Comirnaty COVID-19 vaccine, an mRNA vaccine developed BioNTech, for use in persons 16 years of age and older.  The FDA also stated that use of Comirnaty and the experimental Pfizer-BioNTech mRNA COVID-19 vaccine are interchangeable due to having the same formulation.    

The FDA also stated that use of Comirnaty and the experimental Pfizer-BioNTech mRNA COVID-19 vaccine are interchangeable due to having the same formulation.     However, the FDA also stated that the Pfizer-BioNTech experimental vaccine and the BLA approved Comirnaty were legally distinct, but did not disclose how and why the two vaccines are legally distinct.      As of October 20, 2021 the FDA has now stated that the “vaccine has been known as the Pfizer-BioNTech COVID-19 Vaccine, and will now be marketed as Comirnaty. 

Following FDA approval, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended use of the 2-dose vaccine series in persons 16 years of age and older. 

When a product receives a priority review designation by the FDA, the decision to take action on the application is usually done within 6 months.  In the case of the Pfizer – BioNTech vaccine, the decision to grant full approval was completed in less than four months. 

Prior to granting approval of Comirnaty, the FDA declined to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting  despite previously stating that they were committed to use an advisory committee composed of independent experts to ensure deliberations about authorization or licensure are transparent for the public.” 

In June 2021, a group comprised of international scientists, clinicians, and patient advocate organizations formally submitted a Citizen Petition with the FDA and requested that the regulatory agency delay full approval of COVID-19 vaccines. In their petition, the Coalition Advocating for Adequately Licensed Medicines (CAALM) appealed to the agency to slow down the approval process to ensure that the scientific data was thoroughly assessed. In their petition, the group detailed safety and efficacy criteria that the FDA needed to provide prior to full licensure. These included: 

  • Completion of a minimum follow-up for at least two years of individuals who participated in the clinical trials, including trials that are no longer placebo controlled;
  • Ensuring that evidence is clear that the benefits of vaccination outweigh the risks in specific populations such as in persons with previous SARS-CoV-2 infection, pregnant women, nursing women, infants, children, adolescents as well as in older adults, persons with immunosuppressive disorders, blood disorders, and those with cancer:
  • Requiring a complete safety review of the spike proteins being produced by the body after vaccination, as well as the spike proteins’ full distribution within the body, the pharmacokinetics, and tissue specific toxicity;
  • Completion of vaccine distribution studies at the injection site and the impact of the mRNA technologies in the tissues of the body;
  • A complete assessment and review of all severe adverse events and deaths reported to VAERS and other global vaccine safety monitoring systems following COVID-19 vaccination;
  • Full assessment of the safety of the vaccine in persons receiving more than two vaccine doses;
  • Include experts in gene therapy and delivery in VRBPAC meetings due to the significant differences between gene-based vaccines and traditional vaccines;
  • Ensure that individuals involved in reviewing clinical data submitted to support full approval are free of conflicts of interest with vaccine makers.

The FDA, however, disregarded the request made by the petitioners, and granted full approval of the Pfizer-BioNTech mRNA COVID-19 vaccine in persons 16 years of age and older without addressing the concerns expressed by CAALM.  

Additionally, in the Summary Basis for Regulatory Action Document published to support approval of Comirnaty, the FDA reported that it “did not refer this application to the VRBPAC because our review of the information submitted to this BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.” 

The FDA has also determined that Comirnaty is interchangeable with the Pfizer-BioNTech mRNA vaccine, which also has an EUA status. This means that both vaccines can be used interchangeably in individuals 12 years and older and as a third dose in persons who are immunocompromised.  Following FDA approval, ACIP voted to recommend the 2-dose vaccine series for use in all persons 16 years of age and older. 

Pfizer-BioNTech mRNA COVID-19 Booster doses

In the spring of 2021 Pfizer CEO Albert Bourla reported that a third vaccine dose would likely be needed within 12 months, and annual shots might also be necessary.  On July 8, 2021, the FDA and CDC announced that they were not recommending booster doses, but reported that they were monitoring data. The Federal agencies also stated that they “are prepared for booster doses if and when the science demonstrates that they are needed.” 

One month later, however, the FDA authorized use of a third dose of the Pfizer-BioNTech COVID-19 vaccine in persons with certain immunosuppressive conditions, such as solid organ transplant recipients and individuals with similar conditions. 

On August 18, 2021, Health and Human Services (HHS) announced a plan to begin administration of COVID-19 mRNA booster doses beginning the week of September 20, 2021. Public health officials stated that they would be recommending that the third dose be administered eight months following receipt of the second COVID-19 booster dose. 

Not all public health officials agreed with the booster dose recommendation. Following the White House’s announcement on booster doses, two senior FDA vaccine officials announced their resignations. Their decision to leave the agency was reported to be related to the White House’s announcement on booster doses ahead of the FDA’s completion of review on the data to support this recommendation. 

On September 13, 2021, the Lancet published a report authored by 18 scientists, including several from the World Health Organization and the FDA, against a broad recommendation of mRNA booster doses in the general population. The authors expressed concerns that the introduction of booster doses too soon or too frequently could result in serious immune-related adverse events and may deter acceptance of the use of COVID-19 and other vaccines. While the authors reported that certain populations, such as those with immunosuppressive conditions, may benefit from a booster dose, they indicated that ensuring a primary vaccine series in previously unvaccinated individuals would save more lives than boosting previously vaccinated populations. 

On September 17, 2021, the FDA’s Vaccine and Related Biological Products Advisory Committee (VRBPAC) voted to authorize use of a third booster dose of the Pfizer-BioNTech mRNA COVID-19 vaccine under EUA in persons 65 years of age and older as well as those who are at high risk of severe illness. The booster dose for this population is recommended at 6 months following administration of the second dose. 

The FDA amended the Pfizer-BioNTech EUA on September 22, 2021 and authorized a booster dose in all persons 65 years and older, in individuals 50 through 64 years at high risk for COVID-19, and in persons 18 through 64 “whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.” 

While the CDC’s ACIP voted on September 23, 2021 to recommend booster doses in all persons 65 and older, in persons 50 through 64 years with pre-existing health conditions that put them at increased risk from COVID-19 infection, and in persons 18 through 49 who are at risk of infection due to pre-existing health conditions if the individual believes that they need one, they voted against recommending a booster dose for all persons 18 through 64 years whose living or employment situation places them at high risk for COVID-19 infection. CDC Director Dr. Rochelle Walensky, however, overruled ACIP and went ahead and issued a recommendation for a booster dose of Pfizer-BioNTech COVID-19 vaccine in all persons 18 and older who work or live in high-risk settings. 

Pfizer-BioNTech mRNA COVID-19 Vaccine Profits

In February 2021, Pfizer reported that their expected 2021 earnings from COVID-19 sales were estimated at $15 billion dollars.  However, as of late July 2021, Pfizer had increased its earnings estimate from sales of its COVID-19 vaccine to $33.5 Billion. The company also increased the price per dose of the vaccine from $19.50 to $24.00. 

Pfizer-BioNTech mRNA COVID-19 Vaccine Contamination Concerns

In early September 2021, Japanese health officials reported that “floating matter” was found in five unused vials of COVID-19 vaccines belonging to the same vaccine lot. Vaccines from the same lot continued to be administered after being visually inspected. Pfizer company officials responded by stating that the material was probably undissolved vaccine ingredients and would not impact the safety or efficacy of the product. Additionally, Pfizer also reported that as of September 5, 2021, floating matter had been reported in at least 95 vials. 

Heart Inflammation following mRNA vaccination

In May 2021, Israeli health officials reported a possible link between the Pfizer COVID-19 vaccine and myocarditis after reporting that 62 cases had been reported following vaccination. Of these cases, 56 had occurred following the second shot, and most had involved persons 30 years of age and younger. A Pfizer spokesperson, however, stated that a causal link had not been established and that they had not observed a higher rate of myocarditis post-vaccination then what would have been expected in the overall population. 

On May 17, 2021, the Advisory Committee on Immunization Practices (ACIP) COVID-19 Vaccine Safety Technical (VaST) Work Group met and reviewed information on myocarditis following mRNA vaccines. VaST reported that most of the cases had occurred in teens and young adults, and more cases had occurred in males. Additionally, there were more cases reported after the second vaccine dose, and most occurred on average within four days of vaccination. Members of VaST reported that few cases had been reported but that information on myocarditis following COVID-19 vaccination should be given to vaccine providers. 

Reports of myocarditis and pericarditis following mRNA vaccines continued to increase and on June 11, 2021, the CDC scheduled an emergency ACIP meeting for June 18, 2021 to discuss the higher than expected number of cases. A total of 301 cases following Moderna vaccination and 488 cases following Pfizer vaccination had been reported at the time the meeting was scheduled. 

The meeting, however, was postponed due to the newly created Juneteenth National Independence Day holiday, with the CDC announcing that it would discuss concerns the following week at the regularly scheduled June ACIP meeting.  By the June 23, 2021 meeting, CDC officials reported that through June 11, 2021, 1,226 cases of myocarditis/pericarditis had been reported to VAERS, with 791 occurring after Pfizer vaccination and 435 after Moderna vaccination. Most cases were reported in males, and most occurred following the second dose. 

In the data presented during the June 23, 2021, the CDC reported that in females between the age of 12 and 17 years, after the second dose, the case rate of myocarditis/ pericarditis was 9.1 per million doses administered. In males 12 to 17 years of age, however, the rate after the second vaccine dose was 66.7 per million doses. Cases among females 18 to 24 years old after dose two were reported at 5.5 per million, while after dose two, males of the same age range were affected at a rate of 56.3 per million doses. Most cases of myocarditis/pericarditis resulted in hospitalization, and while most were reported as being resolved, the long-term health outcomes were reported to be unknown.   

The CDC, however, declined to pause use or make changes to the vaccine recommendations, as they reported the benefits to vaccination outweighed the risk. Additionally, they stated that persons with a history of myocarditis and pericarditis could still receive an mRNA vaccine and persons who developed pericarditis after the first mRNA vaccine dose could receive the second dose after symptoms resolved. The CDC also advised that individuals who developed myocarditis after the first dose could consider receiving a second dose under certain circumstances. No data to support this recommendation was provided. 

The FDA reported that the Moderna and Pfizer Fact Sheets would be updated to include a warning of the risk of myocarditis/pericarditis. 

A study of myocarditis after mRNA vaccines on members of the military has found a higher than expected number of cases following vaccination.  Additional studies have also associated mRNA vaccines with heart inflammation, with researchers reporting the need for further investigation. 

A real-world study on the Pfizer-BioNTech vaccine conducted by Israeli scientists found that vaccination most likely caused myocarditis in one to five individuals per 100,000 who would not have developed the condition. Their study also found that young males were at highest risk for developing the condition. 

A preprint study posted on September 8, 2021 on MedRxiv found that teenage boys were most likely to be hospitalized for heart inflammation from mRNA COVID-19 vaccines than from COVID-19 disease. This study was based on filed reports to the Vaccine Adverse Events Reporting System (VAERS) between January 1 and June 18, 2021 in teens between the ages of 12 and 17 years of age. Researchers concluded that: 

“For boys with no underlying health conditions, the chance of either cardiac adverse event (CAE), or hospitalization for CAE, after their second dose of mRNA vaccination are considerably higher than their 120-day risk of COVID-19 hospitalization, even at times of peak disease prevalence. The long-term consequences of this vaccine-associated cardiac inflammation are not yet fully defined and should be studied.”

Study authors suggested that the U.S. could consider a policy change that would delay vaccination in healthy children who have a low risk of developing severe COVID-19 illness or recommend only a single vaccine dose of mRNA vaccine. 

According to the CDC, as of October 6, 2021, 1,640 reports of myocarditis and pericarditis following COVID-19 mRNA vaccines had been reported to VAERS among persons 30 years of age and younger. Most cases have occurred in teenage boys. 

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Dosing Schedules for mRNA COVID-19 vaccines

Both mRNA COVID-19 vaccines are authorized to be given intramuscularly(IM) in a two-dose series. Doses of the Pfizer-BioNTech vaccine should be administered 21 days apart, while doses of the Moderna vaccine are to be given 28 days apart. In early January 2021, following reports in the media of alternative vaccine schedules which included giving a single vaccine dose, giving half doses, and using vaccine brands interchangeably, the FDA issued a press release to emphasize the need for clinicians to follow the authorized EUA dosing schedules. Agency officials reported that without clinical data to support alternative dosing schedules, the public could be put at risk and might ultimately undermine efforts to protect people against COVID-19. 

In contrast, U.K. health officials announced in early January 2021 that it was prioritizing first dose administration to as many people as possible, and delaying the booster dose until more vaccines became available. The U.K. Joint Committee on Vaccination and Immunization (JCVI) stated that: 

“Given the high level of protection afforded by the first dose, models suggest that initially vaccinating a greater number of people with a single dose will prevent more deaths and hospitalizations than vaccinating a smaller number of people with two doses.”

The University of Oxford is currently studying the use of different combinations of COVID-19 vaccines in persons 50 years of age and older. As of October 16, 2021, studies were ongoing to evaluate the safety and effectiveness of using a different COVID-19 vaccine as the second vaccine dose. Vaccines involved in the clinical trials included Pfizer-BioNTech, Moderna, AstraZeneca, and Novavax.  Preliminary results are expected by early summer 2021 but the study is expected to continue for at least one year. 

According to a study published in The Lancet on May 12, 2021, adults 50 years and older who received a mixed dose combination of the Pfizer-BioNTech vaccine and the AstraZeneca COVID-19 vaccines experienced more mild and moderate side effects than those administered only one type of vaccine. Systemic reactions, especially fever, were significantly higher after the second vaccine dose in persons who received the AstraZeneca vaccine followed by a dose of the Pfizer-BioNTech vaccine when compared to persons who received two doses of the Pfizer-BioNTech vaccine. There were also more reports of joint and muscle pain, chills, malaise, fatigue, and headache after the second vaccine dose in person who received a mixed dose schedule. 

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Janssen/Johnson & Johnson COVID-19 Vaccine

In March 2020, Janssen/Johnson & Johnson announced that it had expanded its partnership with BARDA to reach its goal of providing one billion COVID-19 vaccine doses. Company officials reported that human trials of an experimental COVID-19 vaccine utilizing its AdVac® and PER.C6® technologies would likely begin in September 2020.  The AdVac technology uses an adaptation of human Adenovirus 26 to transport the genetic code of the SARS-CoV-2 spike protein into the body to trigger an immune response.    PER.C6 are proprietary cells owned by Janssen Pharmaceutical that were developed in 1985 from retinal cells of an 18-week-old aborted fetus. 

The Janssen/Johnson & Johnson experimental COVID-19 vaccine entered Phase 2 trials in Spain in mid-September 2020.  Clinical trials, however, were halted on October 12, 2020 after a participant developed an “unexplained illness.”  Sources familiar with the event reported that a male in his 20’s had a stroke after receiving the experimental vaccine.  Clinical trials in the U.S  resumed in late October 2020. 

On January 29, 2021, company officials reported that overall, their COVID-19 vaccine was 66 percent effective at preventing moderate to severe symptoms, 85 percent effective at severe illness, and 100 percent effective at preventing COVID-19-related hospitalizations and deaths. 

Janssen/Johnson & Johnson COVID-19 Vaccine EUA

On February 27, 2021, the FDA issued an EUA for Janssen/Johnson & Johnson’s experimental vaccine for use in persons 18 years of age and older. 

Common side effects reported after vaccine administration with the Janssen COVID-19 in clinical trials included injection site pain, headache, fatigue, myalgia, nausea, fever, injection site redness and swelling. 

Serious adverse events reported after vaccine administration included severe pain in the injected arm, hives, hypersensitivity, deep vein thrombosis, pulmonary embolism, transverse sinus thrombosis, severe generalized weakness with fever and headache, tinnitus (ringing or buzzing noises in the ears) and seizures. 

On April 13, 2021, the FDA and CDC paused use of the vaccine after serious blood clots were reported in women between the ages of 18 and 49.  By April 23, 2021, 15 cases and 3 deaths had been associated with the rare blood clot disorder, now referred to by health officials as thrombosis with thrombocytopenia syndrome (TTS). All cases were reported in women, with 2 occurring in women over 50 years of age. The CDC’s Advisory Committee on Immunization Practices (ACIP) voted to resume full use of the vaccine in all persons 18 years of age and older on April 23, 2021, by a vote of 10 to 4 (with one voting member abstaining due to a conflict of interest). Those who voted against the recommendation expressed concern regarding the lack of warning on the risk of TTS in women under 50 years of age.   

On April 23, 2021, the FDA updated the Janssen/Johnson & Johnson’s COVID-19 Fact Sheet and acknowledged that: 

“Reports of adverse events following use of the Janssen COVID-19 Vaccine under emergency use authorization suggest an increased risk of thrombosis involving the cerebral venous sinuses and other sites (including but not limited to the large blood vessels of the abdomen and the veins of the lower extremities) combined with thrombocytopenia and with onset of symptoms approximately one to two weeks after vaccination. Most cases of thrombosis with thrombocytopenia reported following the Janssen COVID-19 Vaccine have occurred in females ages 18 through 49 years; some have been fatal. The clinical course of these events shares features with autoimmune heparin-induced thrombocytopenia. In individuals with suspected thrombosis with thrombocytopenia following the Janssen COVID-19 Vaccine, the use of heparin may be harmful and alternative treatments may be needed. Consultation with hematology specialists is strongly recommended.”

By May 7, 2021, there had been 28 cases of TTS and 3 deaths confirmed by the CDC to be related to the Johnson & Johnson/Janssen COVID-19 vaccine. Moreover, TTS has been reported in men and in women between 50 and 60, in addition to women between 18 and 49 years. 

As of October 6, 2021, 47 cases of TTS following the Janssen/Johnson & Johnson COVID-19 vaccine had been confirmed by the CDC and FDA. 

On July 12, 2021, the FDA announced that it would be issuing a warning that the Johnson & Johnson/Janssen COVID-19 vaccine could trigger Guillain-Barré syndrome (GBS). Health officials have reported 100 cases of GBS following vaccination, with 95 considered serious and requiring hospitalization, and one death. According to the FDA: 

"Although the available evidence suggests an association between the Janssen vaccine and increased risk of GBS, it is insufficient to establish a causal relationship….Importantly, the FDA has evaluated the available information for the Janssen COVID-19 Vaccine and continues to find the known and potential benefits clearly outweigh the known and potential risks."

As of October 6, 2021, 228 cases of GBS following the Janssen/Johnson & Johnson COVID-19 had been identified in the VAERS data. According to the CDC, most cases occurred within 2 weeks of vaccination and among men, primarily those aged 50 and older. 

In early September 2021, the European Medicines Agency reported that its Pharmacovigilance Risk Assessment Committee (PRAC) was investigating a link between the Johnson & Johnson/Janssen COVID-19 vaccine and venous thromboembolism (blood clots in the veins). According to PRAC, in the initial clinical trials of the vaccine, a higher rate of venous thromboembolism was noted in the vaccine group when compared to the placebo group. Additional data collected from two larger clinical trials were expected to be submitted to PRAC in advance of vaccine marketing authorization, to determine whether the condition was linked to vaccination.   

In clinical trials, the vaccine was reported to be 66.9 percent effective in preventing moderate to severe COVID-19 occurring at least 14 days after vaccination and 66.1 percent effective in preventing moderate to severe COVID-19 occurring at least 28 days after vaccination. 

Data is currently not available to determine how long the vaccine will provide protection, and there is no evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person. 

As of the October 8, 2021 CDC release of data, vaccine adverse events submitted to VAERS associated with the Johnson & Johnson/Janssen vaccine totaled 61,939, with 7,982 reports noted as serious. Included in these reports were 1,228 deaths; 1,574 permanent disabilities; 7,948 emergency room visits; and 5,659 hospitalizations. Click for the most current VAERS release data.

Johnson & Johnson/Janssen COVID-19 Vaccine Production Concerns

On March 31, 2021, The New York Times reported that vaccine ingredients were mixed up by employees at an Emergent BioSolutions plant in Baltimore, resulting in up to 15 million ruined Johnson & Johnson vaccine doses. The mistake, which was determined by federal investigators to be the result of “human error”, was caught before any doses were released for distribution. The Baltimore plant was enlisted by the federal government in 2020 to manufacture vaccines developed by both Johnson & Johnson and AstraZeneca. While these vaccines use similar technologies, their ingredients and manufacturing processes are not interchangeable. According to The New York Times, in February 2021, one or more workers erred in the production process that was not discovered by Johnson & Johnson quality control checks for several days. 

This was not the first time that the Emergent BioSolutions Baltimore plant had been cited for errors. In April 2020, an FDA investigator had discovered that employees at the plant lacked adequate training, testing protocols were not being followed, records were not properly secured, and policies to ensure that mix-ups or contaminations would not occur were found to be inadequate. Despite these safety issues, the plant was awarded $628 million by the U.S. government and also secured deals worth more than $740 million with AstraZeneca and Johnson & Johnson to manufacture COVID-19 vaccines for both companies at the Baltimore site. 

On April 20, 2021, the FDA cited the Baltimore Emergent BioSolutions plant for multiple quality control and sanitary issues, including their failure to adequately review and investigate the events that resulted in the manufacturing of 15 million botched Johnson & Johnson vaccine doses. Additionally, the FDA reported that they were not confident that previously released batches of the vaccines were not subject to cross-contamination. Unsanitary conditions at the plant included chipping paint from the walls in the hallways surrounding the manufacturing rooms, “brown residue” on walls, “black residue” and debris on the floor, and congested work areas. Plant employees were noted to be carrying unsealed bags containing medical waste and even “throwing unsealed bags of special medical waste into the service elevator accessing the warehouse corridor.” 

Johnson & Johnson/Janssen COVID-19 Vaccine Profits

In mid-April 2021, Johnson & Johnson reported $100 million in first quarter earnings  from its COVID-19 vaccine.  Company officials have reported that annual vaccine doses will likely be needed for several years. 

Johnson & Johnson/Janssen Booster Doses

On July 8, 2021, the CDC and FDA report that vaccine booster doses were not currently needed but they were continuing to review the data.  However, one month later, in August 2021, a third dose of mRNA COVID-19 vaccine was recommended by the FDA in persons with immunosuppressive conditions such as solid organ transplant recipients. The recommendation did not include the use of a booster dose in immunocompromised individuals who received the Johnson & Johnson/Janssen COVID-19 vaccine. 

As of September 27, 2021, the CDC is reporting that a booster dose of the Johnson & Johnson/Janssen COVID-19 vaccine will likely be needed and that more data on the safety and effectiveness of a booster dose is expected in the near future. 

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Ongoing Vaccine Development

AstraZeneca-University of Oxford COVID-19 vaccine

A vaccine development team from the University of Oxford in the United Kingdom endeavored to make an experimental COVID-19 vaccine candidate by the end of the summer of 2020. On April 23, 2020, human trials of the ChAdOx1 nCoV-19 experimental vaccine using a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein began. 

The University of Oxford reported that the initial clinical trials of ChAdOx1 nCoV-19 would involve 800 individuals. Half would receive the experimental vaccine while the other half would serve as the control group and receive a meningitis vaccine (MenACWY). 

Preliminary results of the AstraZeneca’s Phase 1 and Phase 2 trials were published in July 2020 in The Lancet.  This study involved 1,077 healthy adults between 18 and 55 years of age who were randomly given either the ChAdOx1 nCoV-19 vaccine (AZD1222) or the meningococcal conjugate (MenACWY) vaccine. Systemic and local reactions were more common in the trial group given the experimental COVID-19 vaccine, and a selection of participants from both groups received prophylactic paracetamol (acetaminophen) before vaccinations were administered.

In April 2020, Oxford University partnered with AstraZeneca to develop, manufacture, and distribute the ChAdOx1 nCoV-19 vaccine (now referred to as AZD1222) and U.S. Phase 3 clinical trials began in late August 2020. Their goal was to enroll 30,000 vaccine participants through 62 sites. On September 8, 2020, the pharmaceutical company announced that it was putting the trial on hold after a female participant in the U.K. developed transverse myelitis, a rare but serious neurological disorder, which causes inflammation of the spinal cord.  This was the second time that AZD1222 vaccine trials were placed on hold. In July 2020, trials were paused after a woman developed multiple sclerosis; however, company officials reported that her diagnosis was not related to vaccination. 

While clinical trials resumed quickly in several countries including Great Britain, Japan, South Africa, India,  and Canada,   trials in the U.S. remained on hold until October 23, 2020.  

On October 1, 2020, the European Medicines Agency (EMA) stated that it had started reviewing AstraZeneca’s COVID-19 clinical trial data in real time, and anticipated that following approval, all adults in Britain could receive at least one vaccine dose within 6 months. 

At the January 27, 2021 advisory committee meeting of the U.S. Centers for Disease Control (CDC), company officials from AstraZeneca reported that across the four studies, serious adverse events occurred in 168 participants, with 79 occurring among persons who received the experimental COVID-19 vaccine, and 89 among persons who received either the MenACWY vaccine or saline control. In total, 175 serious adverse events were reported; however, only four events were considered as possibly related to vaccination by clinical trial investigators. Company officials also reported that most solicited adverse events were mild to moderate and the majority resolved within a few days of vaccination. 

The European Union approved the vaccine for use in individuals 18 years and older on January 29, 2021, despite limited data to support its effectiveness in adults over the age 55 years. The University of Oxford and AstraZeneca’s COVID-19 vaccine is estimated to have an efficacy of about 60 percent. 

Health officials in South Africa have halted use of the AstraZeneca COVID-19 vaccine after it was found to be less than 25 percent effective against the B.1.351 variant, which is most common SARS-CoV-2 virus variant circulating in South Africa. 

On March 12, 2021, CNN reported that while AstraZeneca, and UK and European regulators stated there was no evidence of this experimental COVID-19 vaccine causing blot clots, a number of countries had already suspended use of the vaccine. These countries included Denmark, Norway, Iceland, and Thailand. Other countries, like Austria and Italy chose instead to suspend specific batches of the vaccine, while Spain delayed rollout of the AstraZeneca vaccine. 

The World Health Organization (WHO) issued a statement on March 19, 2021 stating that their Global Advisory Committee on Vaccine Safety reviewed data on the vaccine in relation to blood clots and low platelets after vaccination and concluded that the rates of these events are fewer than when they occur naturally in the generalized population. The WHO added and that these events would continue to be monitored. 

Soon thereafter, Canadian health officials joined France and limited the vaccine’s use in persons under 55 years of age, stating “From what is known at this time, there is substantial uncertainty about the benefit of providing AstraZeneca COVID-19 vaccine to adults under 55 years of age,” and had requested a new risk analysis on the vaccine’s risks and benefits broken down by age and gender.  On March 30, 2021, Germany limited its use to persons over the age of 60. 

On April 7, 2021, the European Medicines Agency (EMA) safety committee (PRAC) concluded that “unusual blood clots with low blood platelets should be listed as very rare side effects of Vaxzevria (formerly COVID-19 Vaccine AstraZeneca).” In their report, PRAC reminded health care professionals and vaccine recipients to be aware of the possibility of “blood clots combined with low levels of blood platelets occurring within 2 weeks of vaccination.” PRAC reports that the blood clots occurred in the abdomen (splanchnic vein thrombosis), brain (cerebral venous sinus thrombosis or CVST), and arteries, in conjunction with low levels of blood platelets and at times with bleeding. 

According to PRAC, “One plausible explanation for the combination of blood clots and low blood platelets is an immune response, leading to a condition similar to one seen sometimes in patients treated with heparin (heparin induced thrombocytopenia, HIT).” New studies and revised protocols to ongoing clinical trials have been requested by safety officials. 

In a preprint study pending peer review released on April 20, 2021, German researchers describe what they believe to be the two-step mechanism responsible for the serious clotting reaction following the AstraZeneca COVID-19 vaccine. According to the scientists, the first step involves the activation of blood platelets when they come into contact with the adenovirus outer shell and the proteins from the cells where the vaccine grows. When this occurs in large numbers, a signal wakes up B-cells that then produces an enormous number of antibodies against the platelet factor 4 protein, which is what assists to coordinate blood clotting. The body then believes that it is responding to a huge number of pathogens in the body, and causes antibodies to bind to the platelets, pull in white blood cells, and cause a systemic disruption. The second step involves the calcium-binder and stabilizer, EDTA, that is an ingredient in the AstraZeneca vaccine. EDTA causes the blood vessel walls to open up and permit entry of the protein and platelet complexes to begin circulation in the blood stream which triggers the syndrome. 

While many cases of the serious blood clotting disorder have occurred in women, lead author Dr. Andreas Greinacher reported that this disorder was not specific to one gender. Greinacher noted that since most health-care workers are women and part of the initial group of people to receive the vaccine, the tendency for cases to be reported among females was significantly higher. 

An in-depth review of 24 cases of splanchnic vein thrombosis and 62 cases of cerebral venous sinus thrombosis reported to the EU drug safety database, EudraVigilance, as of March 22, 2021 was completed by the committee. Of these cases, 18 were reported as fatal. The committee, however, continues to recommend the vaccine, stating that “The reported combination of blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.” 

Vaccine use has resumed in many countries; however, some countries have restricted use of the product to persons over the age of 60 or 65 years of age. As of April 19, 2021, the vaccine remained suspended in Cameroon, Norway, and Denmark.  On April 14, 2021, Danish health officials announced that it was halting use of the vaccine after studies had noted that blood clots occurred at a rate of one in 40,000 people. 

As of April 22, 2021, more than 220 cases of blood clots in conjunction with low platelets had been reported by European regulators following AstraZeneca vaccination. 

The AstraZeneca COVID-19 vaccine has also been linked to Guillain-Barré Syndrome (GBS). GBS, a serious neurological disorder where the body’s immune system attacks the peripheral nervous system, can cause muscle weakness, paralysis, and even death. On September 8, 2021, the EMA stated that GBS should be listed as a potential adverse event following vaccination. According to the EMA, as of July 31, 2021, 833 cases of GBS had been reported after AstraZeneca COVID-19 vaccination. 

Inovio Pharmaceuticals INO-4800 DNA vaccine candidate

In early April 2020, Inovio pharmaceuticals began Phase 1 clinical trials of its experimental COVID-19 DNA vaccine, INO-4800. Inovio’s COVID-19 vaccine research has been funded by a $9 million grant from the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) and a $5 million grant from the Bill and Melinda Gates Foundation. It also has a partnership with Philadelphia’s Wistar Institute and Beijing Advaccine Biotechnology Co. in China to develop the vaccine in addition to a $11.9 million contract with the U.S. Department of Defense to provide the experimental DNA coronavirus vaccine for upcoming clinical trials and potential manufacturing of the vaccine for military personnel in the future. 

Inovio’s INO-4800 vaccine injects a small piece of circular DNA, called a plasmid (pGX9501), that encodes for the entire length of the Spike glycoprotein of SARS-CoV-2   to provoke the vaccine recipient’s cells into producing antibodies. The biggest challenge for DNA/RNA vaccines is getting patients’ cells to accept the introduced genetic material. At this point, the most effective technique appears to be electroporation, which is the delivering short pulses of electrical current to the patient to open cell pores and allow the plasmids to enter. This vaccine, unlike many of its counterparts, is stable at room temperature for over a year.    

On June 30, 2020, Inovio Pharmaceutical announced positive results from its Phase 1 clinical trials. Participants received either a 1.0mg or 2.0mg dose administered using INOVIO's CELLECTRA® 2000 device. According to company officials, all 10 reported adverse events were considered Grade 1 and involved localized injection site redness. 

INOVIO’s CELLECTRA® 2000 electroporation device delivers short pulses of electrical current to the patient in addition to the vaccine. The electricity creates temporary pores in a patient’s cell membranes and this process enables the DNA/RNA to enter.    The device is also associated with higher rates of injection site pain in comparison to standard injections.

In late September 2020, the U.S. Food and Drug Administration (FDA) placed the INO-4800 experimental vaccine trials on partial hold and requested more information on the clinical trials and the device used to deliver the vaccine.  While the Phase 3 clinical trials remain on hold as of December 9, 2020, the FDA has permitted Inovio to proceed with Phase 2 clinical trials.

Inovio company officials report that they expect to provide regulators with the answers to any questions by the end of the second quarter of 2021. Vaccine trials, however, are progressing in China in partnership with Advaccine Biopharmaceuticals Suzhou Co Ltd. 

In October 2020, it was reported that Inovio’s experimental COVID-19 vaccine neutralized SARS-CoV-2 viruses with the D614G mutation that had become globally dominate. 

Inovio announced in November 2020 that their INNOVATE Phase 2/3 randomized, blinded, placebo-controlled safety and efficacy trial would be funded by the U.S. Department of Defense and by December of 2020 had published Phase 1 clinical trial data suggesting that the vaccine generated both humoral (neutralizing antibodies) and/or cellular responses in CD4 and CD8 T cells. 

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Novavax COVID-19 Vaccine

Maryland-based Novavax Inc, a biotechnology company which has never successfully delivered a product to market,  has developed an experimental vaccine using recombinant nanoparticle technology. Referred to as a protein subunit vaccine,  NVX‑CoV2373 contains Novavax’s patented saponin-based Matrix-M™ adjuvant designed to enhance the immune response and stimulate high levels of neutralizing antibodies. 

Matrix-M1 contains nm (nanometers) of nanoparticles composed of Quillaja saponins, phospholipid and cholesterol. Quillaja saponins are chemical compounds extracted from the soapbox tree and are used as emulsifiers in food additives and beverages. 

Phase 1/2 clinical trials involved 131 participants, with 83 administered the NVX-CoV2373 vaccine containing the Matrix-M1 adjuvant to help stimulate an immune response to produce a strong antibody response.  Of the remaining trial participants, 25 were given the NVX-CoV2373 vaccine without the Matrix-M1 adjuvant and 23 participants were given a placebo of sterile 0.9 percent normal saline. Participant received two intramuscular injections in the deltoid muscle administered three weeks apart. 

According to the results of the clinical trial, two of the 83 participants (one each in groups D and E) suffered “severe adverse events” (fatigue, headache, and malaise) after the first dose. Two participants—one each in groups A and E—had “reactogenicity events” (malaise, fatigue, and tenderness). Following administration of the second dose, one participant in group D had a “severe local event” (tenderness) and eight participants—one or two in each group—had “severe systemic events.” The most common of these severe systemic events were fatigue and joint pain. One participant in group D developed a fever greater than 100 °F. 

Phase 3 clinical trials of NVX-CoV2373 began in the United Kingdom in late September 2020. This trial, a randomized, placebo-controlled, observer-blinded trial, was expected to enroll up to 10,000 volunteers. Half of the volunteers would be administered two intramuscular doses of the experimental vaccine candidate 21 days apart, while the remaining participants would receive a placebo. 

On November 9, 2020, Novavax received “fast track” status from the U.S. Food and Drug Administration. This designation permitted the company to submit clinical data to the FDA when it became available rather than waiting for all results to be collected. 

In late January 2021, company officials reported that the experimental vaccine was 89.3 percent effective at protecting individuals from illness. This data was based on interim results of late-stage clinical trials conducted in the U.K. The vaccine, however, was found to be only 49.4 percent effective in South African clinical trials, where the B.1.351(Beta) variant was most predominant. 

By February 2021 Novavax had secured a memorandum of understanding with Canada  and Takeda Pharmaceutical Company Ltd.  (Japan) to produce the vaccine, while the European Medicines Agency (EMA) started their rolling reviews of the experimental vaccine.  As Phase 3 trials continued in the United States and the United Kingdom, Novavax had secured advance commitments and purchase agreements totally over 1.2 billion doses of NVX-CoV2373 with GAVI, The Vaccine Alliance (formerly the Global Alliance for Vaccines and Immunization);  Switzerland;   Australia;  New Zealand;  and Canada. 

On March 1, 2021, Novavax released pre-peer reviewed research results on their experimental NVX-CoV2373 vaccine. The Phase 2 component of their Phase 1/2 trial was a randomized placebo controlled trial to identify dosing regimen for the vaccine.

Vaccine arms of about 250 participants received one or two intramuscular doses at 5-μg or 25-μg or placebo, 21 days apart. Subsequent to randomization, 45 percent of participants were 50 to 84 years of age, and side effects were reported as mild and lasted about three days, with intensification after the second dose with the higher dosage of the vaccine.

The lower dose antibody response was reported as 100 percent for all age groups with neutralizing antibody rates exceeding those present in convalescent sera. The study concluded by stating that the two-dose regimen at the lower dose of 5-μg was suited for young and old alike and was highly protective. 

In September 2021, Novavax company officials announced that it was initiating a Phase 1/2 study of a combination COVID-19-seasonal flu vaccine. The clinical trial will combine Novavax' recombinant protein-based NVX-CoV2373 COVID-19 vaccine and their NanoFlu™ vaccine candidates and patented saponin-based Matrix-M™ adjuvant in a single vaccine product.

Clinical trials will involve 640 healthy Australians between 50 and 70 years of age. Trial participants, however, must have previously been infected with SARS-CoV-2 or been vaccinated with an approved COVID-19 vaccine at least eight weeks prior to enrollment in the vaccine trial. Participants will be randomized to different cohorts to evaluate the safety and efficacy of different vaccine formulations and doses. Participants will receive two vaccine doses, spaced 56 days apart. Results from the clinical trial are expected to be available in the first part of 2022. 

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COVID-19 Vaccine Development in China

Convidicea. CanSino Biologics, Inc. of Tianjin, China, in partnership with China’s Academy of Military Medical Sciences’ Institute of Biotechnology, also began development of a COVID-19 vaccine, Convidicea (Ad5-nCoV), that employs a chimpanzee adenovirus vector using the HEK293 cell lines derived from tissue of an aborted fetus. Phase 1 clinical trials of the CanSino vaccine enrolled 108 participants, where 87 of whom (81 percent) experienced at least one adverse reaction within seven days of vaccination. The most common reactions included headache, pain, fever, and fatigue. 

On May 12, 2020, the National Research Council of Canada (NRC) announced a collaborative agreement with the Chinese company to “advance bioprocessing and clinical development in Canada” of Convidicea vaccine.  This agreement, however, was scrapped in late August due to shipping delays. 

By December of 2020, Convidicea clinical trials had been launched in Saudi Arabia,  Moscow,  Mexico,  and Chile,  with advanced purchase agreements totaling 35 million doses.   

Pakistan and Mexico approved Convidicea under emergency prior to approval by any international health organizations and completion of Phase 3 trials in early 2021.     

CoronaVac. Beijing-based Sinovac Biotech Ltd began Phase 3 trials in July of CoronaVac, an inactivated coronavirus vaccine utilizing traditional vaccine manufacturing processes. To develop its vaccine, Sinovac obtained SARS-CoV-2 virus from patients globally, cultured and grew the virus in vero cells, which are derived from monkey kidneys. The virus was then inactivated with beta-propiolactone, a chemical derived from formaldehyde, and prepared and bottled as a vaccine. 

In September 2020, reports indicated that health officials in China had already begun administering experimental COVID-19 vaccines under their emergency use laws to their citizens prior to completion of Phase 3 clinical trials. Frontline healthcare workers, public officials, border security personnel, persons considered high-risk for COVID-19 infection as well as pharmaceutical company officials and their families were first to be given the experimental vaccines. Persons receiving the vaccines were required to sign a “nondisclosure agreement” which would prevent them from sharing any details to the media. 

On November 9, 2020, CoronaVac Phase 3 clinical trials were halted in Brazil due to a death that occurred in a vaccine trial recipient. Two days later, clinical trials resumed, and the death was reported as a suicide that was not related to vaccination. 

As of December 16, 2020, CoronaVac was reported to be 50.65 percent effective against COVID-19 illness in Brazil among health care workers 18 years of age and older. Company officials reported the vaccine to be 91.25 percent effective in clinical trials conducted in Turkey; however, this data was based on a preliminary analysis of only 29 cases. The Indonesia trial reported a vaccine effectiveness of 65.3 percent. China approved the vaccine for use by the general public in early February 2021.  As March 2021 began, CoronaVac is in use or scheduled for use in Tunisia, the Philippines, Mexico, Malaysia, Turkey, Indonesia.  Brazil followed suit in March 2021,  though a week earlier it was reported that a small study awaiting peer-review found that CoronaVac may not be as effective against the new COVID-19 Amazonian variant that is reported as aggressively spreading in Brazil. 

In June 2021, China authorized CoronaVac vaccine for children between the age of 3 and 17 years.  By July 2021, company officials announced that a non-peer reviewed study found that the use of a third vaccine dose invoked a strong immune response and that adverse events were lower than those seen following the initial 2-dose series.

A study published in the Lancet reported an increased risk of Bell’s Palsy following CoronaVac vaccine but that the benefits of vaccination outweighed the risk. 

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Russian COVID-19 Vaccine Development

A COVID-19 vaccine using viral vector technology, Sputnik V, developed in partnership between the Russian research institution, the Gamaleya National Center of Epidemiology and Microbiology, and the Russian Direct Investment Fund, received approval for widespread use by Russian authorities in early August 2020. Sputnik V uses two different strains of adenovirus and requires a second vaccine dose after 21 days to boost the immune response. The Lancet published data on the vaccine’s Phase 1/2 trials on September 4, 2020. Concerns about the lack of transparency related to pre-licensing clinical trial results had been expressed by some in the scientific community. 

On February 2, 2021, interim results from the Sputnik V (Gam-COVID-Vac) Phase 3 trials were published in The Lancet, which reported the vaccine to be 91.6 percent effective at 21 days following administration of the first vaccine dose (on the day that dose 2 was administered). Clinical trials of this vaccine included healthy adults 18 years of age and older who were negative for SARS-CoV-2 at baseline. Seventy serious adverse events were reported among 68 trial participants across both the vaccine group and the control group; however, trial investigators declared that none were related to vaccination. Four deaths occurred during the Phase 3 trials, three in vaccine recipients and one in the placebo group. No deaths were considered to be related to vaccination. Researchers report that the durability of vaccine acquired immunity is not known and it is not known whether the vaccine can halt transmission of SARS-CoV-2. 

In early February 2021, Russian vaccine developers reported that they were in discussions with China’s CanSino Biologics to study whether the second dose of the Sputnik V vaccine could be replaced with the COVID-19 vaccine manufactured by the Chinese vaccine maker. Vaccine researchers are looking to find out if combining COVID-19 vaccines made by different pharmaceutical companies could still offer adequate vaccine acquired immunity, or even better protection against the emerging virus variants. 

By March 2021, Sputnik V vaccine distribution agreements spanned more than 50 countries. On June 17, 2021, company officials reported that a booster dose targeting the Delta variant would soon be available. 

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COVID-19 Variants and Booster Doses

Since the fall of 2020, multiple variants of the SARS-CoV-2 virus have emerged.   U.S. public health officials report that while the current COVID-19 vaccines approved under EUA appear to be effective against the variants, they are in the process of developing guidance to help vaccine manufacturers adapt their products as needed. FDA officials report that:

“For authorized vaccines, our teams are currently deliberating and discussing the types of data needed to support changes in the composition of the vaccine, either through altering the existing vaccine or through the addition of new vaccine component(s), including how sponsors could demonstrate immune response to new variants through streamlined clinical programs that still gather the crucial data the FDA needs to demonstrate effectiveness, but can be executed quickly to gather this data.” 

Pfizer-BioNTech reports its COVID-19 vaccine to be just as effective against the U.K.’s B.1.1.7 (Alpha) as the earlier variant of SARS-CoV-2 virus.  The vaccine, however, appears to be less effective against the South African B.1.351 (Beta) variant.  In April 2021, researchers from Tel Aviv University reported findings of a small study on the effectiveness of the Pfizer-BioNTech vaccine against the B.1.351 (Beta) variant. The study, which was released prior to peer review, found that vaccinated people were eight times more likely to become infected with this SARS-CoV-2 variant than unvaccinated individuals.   

On February 25, 2021, Pfizer-BioNTech announced that they had begun evaluating the safety and effectiveness of a third dose of their COVID-19 vaccine. The study was designed to learn more about the effects of a booster dose on currently circulating and newly emerging SARS-CoV-2 variants. Specifically, Phase 1 clinical trial participants would be offered a 30µg booster dose of the current vaccine 6 to 12 months after completing the two-dose vaccine series. 

Additionally, company officials reported that they were in discussions with the FDA and the European Medicines Agency regarding plans for a clinical study of variant specific vaccines, including a vaccine targeting the South African B.1.351 (Beta) variant. 

Moderna reports that its COVID-19 vaccine appears to offer vaccine-acquired protection against the U.K’s B.1.1.7 (Alpha) variant. The vaccine, however, had a six-fold reduction against the South African B.1.351 (Beta) variant when compared to the initial SARS-CoV-2 virus. 

On February 24, 2021, company officials announced that it had completed manufacturing of materials for a variant-specific vaccine targeting the South African B.1.351 (Beta) variant. Additionally, Moderna stated that they were planning to move forward with two unique study strategies. 

First, Moderna reported planned to evaluate three approaches to boosters. These included: clinical trials of a booster dose of a vaccine targeting the South African B.1.351(Beta) variant; clinical trials of a multi-variant vaccine dose targeting the original SARS-CoV-2 virus and the South African B.1.351(Beta) variant; and clinical trials of a 50µg booster dose of the current vaccine. Second, company officials reported plans to begin studies on the use of the vaccine candidate targeting the South African B.1.351(Beta) variant dose and the experimental multi-variant vaccine dose as a primary vaccination series in persons who are seronegative for SARS-CoV-2. 

Health officials in South Africa have halted use of the AstraZeneca COVID-19 vaccine after the vaccine was found to be less than 25 percent effective against the B.1.351 (Beta) variant, which is most common SARS-CoV-2 virus variant circulating in South Africa. 

On May 4, 2021, the CDC classified the SARS-CoV-2 variant B.1.617 (Delta) and it’s three sub lineages, B.1.617.1, B.1.617.2, and B.1.617.3, as variants of interest.  These variants, which originated in India, were declared variants of concern by the World Health Organization (WHO) on May 10, 2021. According to the WHO, these variants were associated with increased transmissibility and decreased neutralization. As a result, vaccinated individuals and persons who have previously recovered from a COVID-19 infection may be at risk for infection from this variant. 

A technical briefing published by Public Health England on June 11, 2021 noted that almost one third of individuals who died from the COVID-19 Delta variant were fully vaccinated.  In the June 18, 2021 Public Health England Technical report, the death rate in fully vaccinated individuals was 6.6 times higher than among unvaccinated people. 

By the end of June 2021, almost 90 percent of COVID-19 cases in Israel were reported as being from the Delta variant, with 50 percent occurring in fully vaccinated adults.  By late June 2021, Israeli officials report a 30 percent decrease in the vaccine’s ability to prevent infection and mild to moderate illness from COVID-19 disease caused by the Delta variant.   The vaccine’s effective against the Delta variant continued to drop and by the end of July 2021, the vaccine was reported to be only 39 percent effective in Israel. 

On July 27, 2021, the CDC issued a Health Alert Network health advisory regarding the increasing rates of COVID-19 infections related to the Delta variant. In this alert, the CDC noted that the Delta variant accounted for approximately 80 percent of all COVID-19 cases in the U.S. and that fully vaccinated individuals could still become infected and transmit the virus to others. 

Pfizer company officials reported that they would be seeking approval for a third booster dose to target the Delta variant by August 2021. 

On July 8, 2021, the CDC and FDA issued a joint press release stating that COVID-19 vaccine booster doses were not required at this time. They did, however, state that federal health officials were monitoring data and they would continue to inform the public.  However, one month later, in August 2021, the FDA approved use of a third dose of mRNA vaccine in persons with certain immunosuppressive conditions such as solid organ transplant recipients. The CDC’s ACIP recommended use of the third vaccine dose on August 13, 2021. 

One week later, on August 18, 2021, the U.S. Department of Health and Human Services (HHS) released a public statement on a plan for COVID-19 vaccine booster doses beginning September 20, 2021. Public health officials reported that booster doses should be given eight months following the receipt of the second dose of mRNA vaccine. Booster doses of the Johnson & Johnson/Janssen COVID-19 vaccine were also anticipated; however, health officials reported a lack of available data to advise the use of an additional dose.  CDC Director Dr. Rochelle Walensky also reported that annual COVID-19 vaccine doses were not anticipated because health officials believe that a third dose will provide sufficient long-term protection. 

Prior to the September 17, 2021 FDA Vaccine and Related Biological Products Advisory Committee (VRBPAC) meeting, Pfizer released data showing that the COVID-19 vaccine waned by 6 percent each month and reported that within 6 to 8 months, the vaccine offered limited protection. Company officials also acknowledged that the failure of the vaccine to protect individuals was related to waning vaccine effectiveness and not because of escaping protection from the Delta variant. 

On September 17, 2021, VRBPAC voted to authorize use of a third booster dose of the Pfizer-BioNTech mRNA COVID-19 vaccine under EUA in persons 65 years of age and older as well as those who are at high risk of severe illness. The booster dose for this population is recommended at 6 months following administration of the second dose. 

The FDA amended the Pfizer-BioNTech EUA on September 22, 2021 and authorized a booster dose in all persons 65 years and older, in individuals 50 through 64 years at high risk for COVID-19, and in persons 18 through 64 “whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.” 

While the CDC’s ACIP voted on September 23, 2021 to recommend booster doses in all persons 65 and older, in persons 50 through 64 years with pre-existing health conditions that put them at increased risk from COVID-19 infection, and in persons 18 through 49 who are at risk of infection due to pre-existing health conditions if the individual believes that they need one, they voted against recommending a booster dose for all persons 18 through 64 years whose living or employment situation places them at high risk for COVID-19 infection. CDC Director Dr. Rochelle Walensky, however, overruled ACIP and went ahead and issued a recommendation for a booster dose of Pfizer-BioNTech COVID-19 vaccine in all persons 18 and older who work or live in high-risk settings. 

According to a pre-peer review study conducted by researchers from the Mayo Clinic and nference, a data analytics company, by July 2021, the Pfizer-BioNTech COVID-19 vaccine was reported to be only 42 percent, while the Moderna was reported to be 76 percent effective. This study was conducted during a time when approximately 70 percent of the case were reported as being of the Delta variant.  A CDC study published in mid-August 2021 reported that among nursing care facility residents, mRNA vaccines were only 53.1 percent effective against the Delta variant. 

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COVID-19 Vaccine Allocation

On October 2, 2020, the National Academies of Sciences, Engineering, and Medicine released its final report which recommended a four-phase plan for the equitable allotment of a COVID-19 vaccine. According to the plan outlined by the Academies, during the time when vaccine supply is limited, the following phases of vaccine administration should be followed “to maximize societal benefit by reducing morbidity and mortality caused by the transmission of SARS-CoV-2.” 

  • Phase 1a – Front-line health care workers who are at risk of exposure to SARS-  CoV-2 and of transmitting the virus to others.
  • Phase 1b – Persons of all ages with underlying health conditions and comorbidities which places them at a high risk of severe illness or death from COVID-19. This also includes persons 65 years of age and older who are living in group settings which include nursing homes, jails, shelters, etc.
  • Phase 2 – Essential workers, including childcare workers, school staff, and K-12 teachers. Persons considered at moderate risk of severe illness are also included in this group. Phase 2 also includes any persons 65 and older not included in Phase 1.
  • Phase 3 – Children and young adults, as well as persons who work in areas considered to be at a moderate high risk of exposure but at low risk for severe illness.
  • Phase 4 – Any remaining individuals.

Notably, the above recommended allocation plan would distribute COVID-19 vaccines to individuals with underlying health conditions and morbidities that had been identified by the National Academies of Sciences, Engineering, and Medicine as placing them at higher risk for severe complications from COVID-19, despite the fact that these vaccines were not tested on these at-risk populations. In real-world terms, because experimental COVID-19 vaccine clinical trials were conducted with healthy individuals, the potential for vaccine adverse events in at-risk populations are unknown. 

On December 1, 2020, the CDC’s Advisory Committee on Immunization Practices (ACIP), which makes non-binding use recommendations that may be adopted by the CDC, recommended that both health care providers and residents of long-term care facilities be offered COVID-19 vaccination in the initial phase (Phase 1a) of vaccine distribution. 

ACIP updated its COVID-19 vaccine allocation recommendations on December 20, 2020, and stated that in the second phase of the vaccine allocation (Phase 1b), persons 75 years of age and older and non-healthcare frontline workers should receive the vaccine. The third phase of vaccine allocation (Phase 1c) recommendations included persons aged 65 to 74, persons between 16 and 64 years with high-risk medical conditions, and essential workers who were not included in the Phase 1b rollout. 

As of May 12, 2021, all persons 12 years of age and older were considered eligible for the COVID-19 vaccine and the CDC reports that vaccines are widely availability in the U.S. 

A third dose of mRNA vaccine has also been authorized for use by the FDA and recommended by ACIP for use in persons with certain immunosuppressive conditions such as solid organ transplant recipients and in persons with similar immunocompromising conditions. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

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Updated October 20, 2021

 

How effective are COVID-19 vaccines?

vaccine effectiveness

FDA COVID-19 Vaccine Approval Considerations

On June 30, 2020, the U.S. Food and Drug Administration (FDA) stated that a COVID-19 vaccine would only receive approval if it were at least 50 percent more effective than a placebo at either preventing infection or reducing illness severity. 

The FDA released its guidance for industry regarding Emergency Use Authorization (EUA) approval for COVID-19 vaccines on October 6, 2020, and stated that it would be requiring that at least half of all Phase 3 clinical trial participants be followed for at least two months following administration of the second vaccine dose. The FDA also requested that vaccine manufacturers submit information on a minimum of five cases of severe COVID-19 disease among individuals who received the placebo. 

However, vaccine trial designs have faced criticism and in October of 2020 the British Medical Journal (BMJ) noted that Phase 3 trials for Moderna, Pfizer, AstraZeneca COVID-19 vaccines would not answer basic questions around preventing infection and reducing the likelihood of severe illness. 

A September 2020 article in Forbes by noted biologist William Haseltine, PhD  revealed that COVID-19 vaccine studies by Moderna, Pfizer, AstraZeneca and Johnson & Johnson intend “to complete interim and primary analyses that at most include 164 participants.”  

According to Dr. Haseltine, with an efficacy success requirement of 70 percent, this equates to interim analysis based on the results of infection ranging from 32 (Moderna) vaccine to 77 (Johnson & Johnson) vaccine recipients. Dr. Haseltine concluded by saying that COVID-19 vaccine trials were in essence designed to succeed. The article also contained many of the same concerns noted in the October 2020 BMJ article and added that “vaccines currently under trial will not be the silver bullet” ending the pandemic. 

 

Durability of Vaccine Acquired Immunity

In February 2021, the CDC stated that currently available mRNA COVID-19 vaccines are believed to offer fully vaccinated individuals at least three months of vaccine-acquired immunity. In their quarantine guidance released on February 11, 2021, the CDC stated that fully vaccinated people (those who have received two doses of COVID-19 vaccine) who are exposed to SARS-CoV-2 through close contact are not required to quarantine as long as vaccination has occurred within three months and they remain asymptomatic. 

However, in March 2021 the CDC’s website stated that it is unknown how effective, or for what length of time experimental COVID-19 vaccines would provide immunity against COVID 19 illness. The website also reported that it is also unknown how effective the vaccine will be in mediating the severity of illness, should the vaccine fail to prevent COVID-19.   

On April 27, 2021, fully vaccinated individuals were still being told that they must stay at least 6 feet apart from others; wear masks in certain outdoor crowded public settings and indoor public settings; and when in gatherings with unvaccinated individuals. Vaccinated individuals were also being told to take precautions when visiting unvaccinated individuals who are at an increased risk for severe COVID-19 disease and to be vigilant about symptoms and get tested when they occur. The CDC, however, stated that vaccinated individuals could travel domestically and internationally without quarantining, and that pre- and post- travel testing was not required, unless the international destination required it. Persons entering the U.S., however, were still required to show a negative COVID-19 test result before boarding a flight and testing was still advised 3-5 days following international travel. 

In May 2021, the CDC announced that fully vaccinated individuals could resume activities without masking or physically distancing, except where required by law, workplace or local requirements. Additionally, they could travel domestically without testing or self-quarantine, and travel internationally without testing unless their destination required it, and would not be required to self-quarantine on return. Vaccinated persons exposed to someone with SARS-CoV-2 were also advised that they would not need to self-quarantine or test unless symptomatic. 

Since emergency use of the experimental COVID-19 vaccines was authorized by the FDA in December 2020, there have been reports of fully vaccinated individuals testing positive for SARS-CoV-2. In late January 2021, Congressman Stephen Lynch of Massachusetts tested positive for the virus despite receiving the two recommended vaccine doses earlier in the month.  Four individuals from Oregon also tested positive for the virus two weeks after receiving the second vaccine dose. Health officials reported their symptoms to range from none to mild. 

In early April 2021, Michigan health officials reported that between Jan 1 and March 31, 2021, at least 246 Michigan residents considered fully vaccinated against COVID-19 had tested positive for the virus, and three individuals had died. 

As of April 30, 2021, 10,262 cases of COVID-19 had been reported in fully vaccinated individuals, and included 995 hospitalizations, and 160 deaths. The CDC has acknowledged that the number of breakthrough cases is likely much higher since the reporting system is passive and voluntary, and relies on local and state health departments to provide this information. 

In late April 2021, the CDC announced that it was only going to be reporting the number of breakthrough cases that resulted in hospitalization and death “to help maximize the quality of the data collected on cases of greatest clinical and public health importance.”  As a result, the public will not be made aware of the actual number of reported breakthrough cases occurring fully vaccinated individuals.

On July 27, 2021, the CDC issued a health alert and reported that fully vaccinated individuals could still become infected and be capable of transmitting the virus to others. Public health officials reported that the SARS-CoV-2 variants currently circulating in the U.S., especially the Delta variant, were highly transmissible and increasing rate of infections. The CDC also recommended that all persons, including fully vaccinated individuals, should wear masks in public indoor spaces in communities with high or substantial transmission rates. 

While this health alert reported that most COVID-19 cases, hospitalizations, and deaths were occurring in unvaccinated individuals,  data released from an outbreak in Massachusetts reported that 74 percent of cases occurred in fully vaccinated individuals. Additionally, four of the five hospitalizations reported during this study occurred in fully vaccinated individuals. 

As of October 12, 2021, there have been 24,717 hospitalizations and 7,178 deaths in SARS-CoV-2 positive individuals who were reported to be fully vaccinated. The CDC reports that 3,647 (15 percent) of hospitalizations and 951 (13 percent) of deaths were not directly attributed to COVID-19. 

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Pfizer-BioNTech COVID-19 Vaccine EUA

On December 11, 2020, the FDA issued an EUA for Pfizer-BioNTech’s messenger RNA (mRNA) COVID-19 Vaccine for use in persons 16 years of age and older. 

According to a press release issued by Pfizer-BioNTech on November 9, 2020, the efficacy rate of their COVID-19 vaccine was over 90 percent “at 7 days after the second dose” in trial participants who had no prior history of SARS-CoV-2 infection.  It is not yet known how long vaccine-acquired immunity from the Pfizer-BioNTech vaccine will persist. 

In data submitted to the FDA, Pfizer-BioNTech reported that 170 cases of laboratory confirmed SARS-CoV-2 infections had occurred in clinical trial participants, with eight reported in the vaccine group, and 162 in the placebo group. However, clinical data also reported a category of disease referred to as “suspected COVID-19” illness. This category involved persons who had symptoms of COVID-19 but were not laboratory confirmed. In the Pfizer study, 3410 cases of suspected COVID-19 were reported, with 1,594 occurring in the vaccine group, and 1,816 in the placebo arm. 

In a published editorial, associate editor of the British Medical Journal (BMJ), Dr. Peter Doshi, questioned Pfizer-BioNTech’s efficacy data: 

“With 20 times more suspected than confirmed cases, this category of disease cannot be ignored simply because there was no positive PCR test result. Indeed this makes it all the more urgent to understand. A rough estimate of vaccine efficacy against developing covid-19 symptoms, with or without a positive PCR test result, would be a relative risk reduction of 19% (see footnote)—far below the 50% effectiveness threshold for authorization set by regulators. Even after removing cases occurring within 7 days of vaccination (409 on Pfizer’s vaccine vs. 287 on placebo), which should include the majority of symptoms due to short-term vaccine reactogenicity, vaccine efficacy remains low: 29% (see footnote).”

(Footnote - Calculations in this article are as follows:  19% = 1 – (8+1594)/(162+1816); 29% = 1 – (8 + 1594 – 409)/(162 + 1816 – 287). I ignored denominators as they are similar between groups.) 

Doshi also noted that clinical trials were not designed to determine whether the COVID-19 vaccine could stop transmission of the SARS-CoV-2 virus, and that evaluation of the impact of the vaccine on the reduction of hospitalizations and deaths should be performed. Clinical trial data also revealed that eight people who previously tested positive for SARS-CoV-2 were found to have confirmed, symptomatic COVID-19 illness post-vaccination. This included one person in the vaccine arm, and seven in the placebo group. These results may indicate that COVID-19 vaccines might not prevent reinfection in previously infected individuals. In addition, Doshi stated that false negative PCR test results would significantly decrease the vaccine’s efficacy, as well as that “suspected” COVID-19 cases may be due to other viruses. 

There is also insufficient data to support the use of Pfizer-BioNTech’s COVID-19 vaccine in persons who are positive for SARS-CoV-2 at the time of vaccination. In clinical trials, there was one case of COVID-19 illness in both the vaccine group and the placebo group in persons who were found to be positive for SARS-CoV-2 at baseline. Based on the limited data of this sub-population provided to the FDA by Pfizer-BioNTech, the vaccine efficacy in this population was reported at -7.1 percent (Confidence Ratio -8309.9, 98.6). 

While the FDA approved use of the experimental vaccine in 16 and 17-year-old individuals, in clinical trials, only 153 adolescents were enrolled, with 77 receiving the vaccine, and 76 receiving the placebo.  In the spring of 2021, Pfizer-BioNTech began testing their product for use in children 12 to 15 years of age.  According to a press release issued by Pfizer on March 31, 2021, the vaccine was reported to be 100 percent effective in this population, based on a study of 2,260 adolescents 12 to 15 years of age.  On April 9, 2021, company officials announced that they had submitted a request to the FDA for approval of the vaccine for use in this population. 

On May 10, 2021, the FDA expanded the EUA granted Pfizer/BioNTech to distribute its experimental mRNA vaccine in the U.S. to include administration to children as young as 12 years old  and the CDC’s ACIP voted to approve its use in this population on May 12, 2021. 

The approval for use in adolescents 12 to 15 years was based on a small clinical trial involving 2,260 teens, of which 1,131 received the vaccine and 1,129 received a saline placebo.  According to data provided by the vaccine manufacturer, the vaccine was reported to be 100 percent effective at preventing COVID-19. In the clinical trial, there were no cases of COVID-19 in the vaccine arm and 18 cases in the placebo arm. There were no cases of severe COVID-19 illness or death reported among clinical trial participants. 

In late March 2021, phase 1/2/3 clinical trials of the Pfizer-BioNTech vaccine in infants and children 6 months to 11 years of age were initiated. According to the press release issued on March 31, 2021, “the study is evaluating the safety, tolerability, and immunogenicity of the Pfizer-BioNTech COVID-19 vaccine on a two-dose schedule (approximately 21 days apart) in three age groups: children aged 5 to 11 years, 2 to 5 years, and 6 months to 2 years.”      

Complete study data from the clinical trials are not currently available for review. Officials from Pfizer-BioNTech have stated that they will only begin to make the data public two years following completion of the study, though the experimental vaccine is in use within the general population. 

The Pfizer-BioNTech COVID-19 vaccine must be shipped and stored between -80ºC to -60ºC (-112ºF to -76ºF) and protected from light until ready to use.  However, on February 25, 2021, the FDA announced that frozen undiluted vials of the Pfizer-BioNTech COVID-19 could also be transported and stored at temperatures typically found  in pharmaceutical freezers for up to 14 days.  Mishandling of the vaccine during any step of the distribution process may result in an ineffective vaccine product.   Temperature storage and shipping guidelines were updated again on May 19, 2021, which permitted undiluted, thawed vaccines to be stored at refrigerator temperatures, 2°C to 8°C (35°F to 46°F), for up to 1 month. 

Pfizer-BioNTech also reports its COVID-19 vaccine to be just as effective against the U.K.’s B.1.1.7(Alpha) variant of SARS-CoV-2 virus.  However, preliminary data from a study conducted by the University of Cambridge has found the vaccine to be less effective against the South African B.1.351 (Beta) SARS-CoV-2 virus variant.  In April 2021, researchers from Tel Aviv University reported findings of a small study on the effectiveness of the Pfizer-BioNTech vaccine against the B.1.351 (Beta) variant. The study, which was released prior to peer review, found that vaccinated people were eight times more likely to become infected with this SARS-CoV-2 variant than unvaccinated individuals.   

Pfizer-BioNTech COVID-19 Booster Doses

On February 25, 2021, company officials announced that they had begun evaluating the safety and effectiveness of a third dose of their COVID-19 vaccine. The study was aimed at learning more on the effects of a booster dose for currently circulating and newly emerging SARS-CoV-2 variants. Specifically, Phase 1 clinical trial participants would be offered a 30µg booster dose of the current vaccine 6 to 12 months after completing the two-dose vaccine series. 

Additionally, Pfizer-BioNTech reported that they were in discussions with the FDA and the European Medicines Agency regarding plans for a clinical study of variant specific vaccines, including a vaccine targeting the South African B.1.351 (Beta) variant. 

In early March 2021, a small exploratory study out of New York University’s Grossman School of Medicine found that persons already recovered from SARS-CoV-2 virus infection receiving one dose of the vaccine produced more neutralizing antibodies to defend against future SARS-CoV-2 infection in comparison to persons who have not been infected with the SARS-CoV-2 virus and who had received two doses of the vaccine. The exploratory study may indicate that vaccination of persons who have already experienced SARS-CoV-2 infection may only need one dose of the Pfizer-BioNTech experimental COVID-19 vaccine. The study’s author added that these findings needed to be confirmed in larger studies. 

In April 2021, Pfizer CEO Albert Bourla reported that a third vaccine dose would likely be needed within 12 months, and annual shots might also be necessary. Pfizer also reported that studies have shown the vaccine to be 93.1 percent effective six months after the second dose is administered. 

In late June 2021, Israeli health officials reported the Pfizer-BioNTech COVID-19 vaccine to be 64 percent effective against the SARS-CoV-2 variant B.1.617 (Delta).   By late July 2021, the vaccine’s effectiveness against the Delta variant in Israel had decreased to only 39 percent. 

A large pre-peer reviewed study out of Israel posted on August 25, 2021 in MedRxiv reported that after three months post-vaccination, the risk of infection from SARS-CoV-2 was reported to be 13.06 times higher in vaccinated individuals. Additionally, vaccinated persons were 27 times more likely to show symptoms in comparison to persons who had previously been diagnosed with COVID-19. The study also found that participants who had received the 2-dose series were 5.96 times more likely to be infected and 7.13 times more likely to experience COVID-19 symptoms such as shortness of breath, cough, and fever. 

According to a pre-peer review study conducted by researchers from the Mayo Clinic and nference, a data analytics company, by July 2021, the Pfizer-BioNTech COVID-19 vaccine was reported to be only 42 percent. This study was conducted during a time when approximately 70 percent of the cases were reported as being of the Delta variant. 

On July 8, 2021, federal health officials announced that booster doses were not needed but that they planned to continue to monitor the data and advise the public as needed.  However, one month later, the FDA authorized use of a third vaccine dose in persons with certain immunosuppressive conditions such as solid organ transplant recipients. The CDC’s ACIP recommended use of the third dose in the population on August 13, 2021. 

On August 16, 2021, Pfizer-BioNTech announced that it had submitted data to the FDA to support the use of a COVID-19 booster dose. According to the press release issued by Pfizer, administration of a third COVID-19 vaccine dose produced higher levels of neutralizing antibody titers against the original SARS-CoV-2 virus as well as the Beta and Delta variants, in comparison to levels elicited following receipt of the 2-dose series. Company officials also reported that administration of a booster dose produced neutralizing antibody titers for variants that were equivalent to the wild type. 

On September 17, 2021, the FDA’s Vaccine and Related Biological Products Advisory Committee (VRBPAC) voted to authorize use of a third booster dose of the Pfizer-BioNTech mRNA COVID-19 vaccine under EUA in persons 65 years of age and older as well as those who are at high risk of severe illness. The booster dose for this population was recommended 6 months following administration of the second dose.  The FDA amended the Pfizer-BioNTech EUA on September 22, 2021 and authorized a booster dose in all persons 65 years and older, in individuals 50 through 64 years at high risk for COVID-19, and in persons 18 through 64 “whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.” 

While the CDC’s ACIP voted on September 23, 2021 to recommend booster doses in all persons 65 and older, in persons 50 through 64 years with pre-existing health conditions that put them at increased risk from COVID-19 infection, and in persons 18 through 49 who are at risk of infection due to pre-existing health conditions if the individual believes that they need one, they voted against recommending a booster dose for all persons 18 through 64 years whose living or employment situation places them at high risk for COVID-19 infection. CDC Director Dr. Rochelle Walensky, however, overruled ACIP and went ahead and issued a recommendation for a booster dose of Pfizer-BioNTech COVID-19 vaccine in all persons 18 and older who work or live in high-risk settings. 

A study funded by Pfizer and published in the Lancet on October 4, 2021 reported that after six months, the vaccine was only 47 percent effective at preventing infection. Study authors, however, report the vaccine to be 93 percent effective against COVID-19 hospitalization. The declining effectiveness of the vaccine was blamed on vaccine waning rather than on the variants. 

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Janssen/Johnson & Johnson Pharmaceutical COVID-19 Vaccine

On February 27, 2021, the FDA issued an EUA for Janssen/Johnson & Johnson’s experimental vaccine for use in persons 18 years of age and older. 

In clinical trials, the vaccine was 67 percent effective in preventing moderate to severe COVID-19 occurring at least 14 days after vaccination and 66 percent effective in preventing moderate to severe COVID-19 occurring at least 28 days after vaccination.  The vaccine, however, was reported to be only 42 percent effective in persons over the age of 60 who have underlying health conditions. 

Janssen/Johnson & Johnson’s experimental vaccine, Ad26.COV2.S (or JNJ-78436725), is also a non-replicating viral vector vaccine that uses AdVac® and PER.C6® technologies.  AdVac technology uses an adaptation of human Adenovirus 26 to transport the genetic code of the SARS-CoV-2 spike protein into the body to trigger an immune response.    PER.C6 are proprietary cells owned by Janssen Pharmaceutical that were developed in 1985 from retinal cells of an 18-week-old aborted fetus. 

According to a press release issued on January 29, 2021 by the National Institutes of Health: 

“The investigational vaccine was reportedly 66% effective at preventing the study’s combined endpoints of moderate and severe COVID-19 at 28 days post-vaccination among all volunteers, including those infected with an emerging viral variant. Moderate COVID-19 was defined as laboratory-confirmed SARS-CoV-2 plus either one of the following: evidence of pneumonia; deep vein thrombosis; difficulty breathing; abnormal oxygen saturation or a respiratory rate equal to or greater than 20; or two or more signs or symptoms suggestive of COVID-19, such as cough, sore throat, fever or chills. Severe COVID-19 was defined as laboratory-confirmed SARS-CoV-2 plus evidence of clinical signs at rest indicative of severe systemic illness, respiratory failure, shock, significant organ dysfunction, hospital intensive care unit admission or death.

Geographically, the level of protection for the combined endpoints of moderate and severe disease varied: 72% in the United States; 66% in Latin American countries; and 57% in South Africa, 28 days post-vaccination. The investigational vaccine was reportedly 85% effective in preventing severe/critical COVID-19 across all geographical regions. No deaths related to COVID-19 were reported in the vaccine group, while 5 deaths in the placebo group were related to COVID-19. Overall, there were 16 deaths in the placebo group, and 3 deaths in the vaccine group.”

Data is currently not available to determine how long the Janssen/Johnson & Johnson vaccine will provide protection, and there is no evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person. 

In February 2021, company officials reported that annual vaccine doses will likely be needed for several years.  While a third dose of mRNA COVID-19 vaccine was recommended in persons with certain immunosuppressive conditions such as solid organ transplant recipients, as of August 12, 2021, no additional doses of the Johnson and Johnson/Janssen COVID-19 vaccine have been authorized by the FDA. 

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University of Oxford and AstraZeneca’s Viral Vector COVID-19 vaccine

Viral vectored vaccines genetically engineer live viruses, such as adenoviruses, to include the SARS-CoV-2 spike protein code. The engineered viruses are then used as a vector (delivery method) to get the altered genetic code inside the cell.  This stimulates the cell’s ribosome to produce SARS-CoV-2 protein antigen that is recognized by the immune system and triggers an immune response. 

The University of Oxford and AstraZeneca’s have developed a non-replicating viral vector vaccine that uses a chimpanzee adenovirus to express the SARS-CoV-2 protein. 

On January 29, 2021, the European Union approved the vaccine for use in individuals 18 years and older despite limited data to support its effectiveness in adults over the age 55 years. The University of Oxford and AstraZeneca’s COVID-19 vaccine is estimated to have an efficacy of about 60 percent.  Health officials in Germany, however, are not recommending use of the vaccine in adults 65 years of age and older after concluding that there is not enough data to determine whether the vaccine is effective in this population. 

Health officials in South Africa halted use of the experimental AstraZeneca COVID-19 vaccine after it was found to be less than 25 percent effective against the B.1.351 variant, which is most common SARS-CoV-2 virus variant circulating in South Africa. 

On March 22, 2021, it was reported that the experimental vaccine was 79 percent effective. However, on March 23, 2021, Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID) stated that AstraZeneca’s press release on their COVID-19 vaccine was misleading and contained outdated information. AstraZeneca was urged by NIAID to work with the Data and Safety Monitoring Board “to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible."   

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Updated October 20, 2021

 

Can COVID-19 vaccines cause injuries and death?

vaccine injury death

According to the U.S. Department of Health and Human Services, adverse events are classified into five grades. The guidelines are as follows:

  • Grade 1 - Considered mild or asymptomatic and no intervention is required
  • Grade 2 - A moderate event but minimal, local or noninvasive interventions are needed indicated. In some situations, certain activities of daily living are limited (shopping, meal preparations, using the telephone).
  • Grade 3 - Considered a severe or medically significant adverse event but not one that is considered  immediately life-threatening. In certain cases, hospitalization, including long-term hospitalization is needed. Grade 3 reactions are disabling and limit a person’s ability to perform activities of daily living (feeding self, bathing, self-care). 
  • Grade 4 - A life-threatening event where urgent intervention is required  
  • Grade 5 - Death related to an adverse event

 

COVID-19 Vaccines in the U.S.

Under EUA authority, the FDA Commissioner may permit “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN (CBRN = chemical, biological, radiological, nuclear) threat agents when there are no adequate, approved, and available alternatives.” 

Currently, all COVID-19 vaccines in use in the United States have an EUA status. To learn more about EUA products and vaccines and consumer rights, visit NVIC’s FAQ on Emergency Use Vaccines (EUA) & Vaccine Injury Compensation.

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Pfizer - BioNTech mRNA COVID-19 Vaccine

Pfizer - BioNTech Vaccine Trial Data

More than 50 percent of adult participants involved in the Phase 1/2 human trials of Pfizer and BioNTech’s experimental messenger RNA (ribonucleic acid) COVID-19 vaccine reported adverse reactions. This trial, which was conducted in May and June 2020, involved 45 healthy adults between the ages of 18 and 55 years. Limitations of this data were noted as not accurately reflecting populations at highest risk for COVID-19. 

In the trials, 12 adults received a 10-microgram dose of the BNT162b1 vaccine, 12 adults were injected with a 30-µg dose, 12 received a 100-µg dose, while nine adults were given a placebo of a sterile saline solution (0.9 percent sodium chloride injection, in a 0.5-mL dose). Within seven days of vaccination, seven (58.3 percent) of the participants in the 10-µg group reported adverse reactions (pain) near the injection site and 24–or 100 percent–in the 30-µg and 100-µg groups and two (22.2 percent) in the placebo group reported reactions. Severe pain was reported by one participant who received 100-µg dose.   

Three weeks after the initial vaccination with the Pfizer-BioNTech experimental vaccine, all clinical trial participants were given a second dose of the vaccine at the same dosage. Of the participants in the 10-µg group, 8.3 percent developed fevers. Of those in the 30-µg group, 75 percent developed fevers. More than 50 percent of the adults, who were given either a 10-µg or 30-µg dose, experienced an adverse reaction such as sleep disturbances and fever. Two participants suffered severe reactions. A Grade 3 fever of over 101.3°F two days after vaccination was experienced by one adult in the 30-µg group and sleep disturbance one day after vaccination was experienced by one adult in the 100-µg group.   

Pfizer reported early U.S. Phase 3 clinical trials results in mid-September. Company executives presented safety data for 5,664 individuals between 18 and 64 years of age, and 1,816 persons between 65 and 85 years who received one dose. In the younger age category, 16 percent reported chills, 35 percent complained of headache and 38 percent reported fatigue following vaccination. Eleven percent or less suffered diarrhea, joint pain, or chills. Side effects were reportedly lower among persons aged 65 to 85 years. 

After the second vaccine dose, 36 percent of trial participants between the ages of 18 and 64 reported fatigue, while 28 percent reported a headache and 18 percent reported muscle pain. Most adverse effects following the second dose were reported as mild to moderate; however, some participants did experience severe or life-threatening adverse reactions. Severe side effects occurred more frequently after the second dose. 

On December 11, 2020, the FDA issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech’s messenger RNA (mRNA) COVID-19 vaccine for use in persons 16 years of age and older. 

According to the Fact Sheet for Healthcare Providers Administering the Pfizer-BioNTech COVID-19 vaccine: 

“In clinical studies, adverse reactions in participants 16 years of age and older included pain at the injection site (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%), injection site swelling (10.5%), injection site redness (9.5%), nausea (1.1%), malaise (0.5%), and lymphadenopathy (0.3%).”

Additional adverse events reported in clinical trials included 12 cases of appendicitis (eight in the vaccine group vs. four in the placebo group), 70 cases of  lymphadenopathy (64 in the vaccine group vs. 6 in the placebo group), and four cases of Bell’s Palsy, all in the vaccine group.

Six deaths occurred during the clinical trials, two in the vaccine arm and four in the placebo arm. Of the two deaths in the vaccine arm, one person was reported as having a cardiac arrest 62 days post Dose 2 and the other was reported as atherosclerotic disease and died three days after Dose 1. 

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Pfizer - BioNTech Vaccine and Anaphylaxis

Immediately following the FDA issuance of an EUA for Pfizer-BioNTech’s COVID-19 vaccines, reports of anaphylaxis began to appear in the media.

Between December 14 and 23, 2020, 21 cases of anaphylaxis were reported to the Vaccine Adverse Events Reporting System (VAERS), with 71 percent occurring within 15 minutes of vaccine administration. Of these cases, 17 reports were in persons with a past history of allergic reaction, including seven who had previously reported a history of anaphylaxis. A total of 4,393 adverse events were reported to VAERS, including 175 significant events that were identified for additional review as possible cases of severe allergic reactions. Eighty-six of these cases were considered by health officials to be non-anaphylaxis allergic reactions, and 61 were reported as nonallergic adverse events. Public health officials reported that anaphylaxis following Pfizer-BioNTech’s COVID-19 vaccine occurred at a rate of 11.1 cases per million doses administered. 

On December 30, 2020, four Kentucky seniors died on the same day that they received the Pfizer-BioNTech COVID-19 vaccine. Of the four seniors who passed away, three had previously tested positive for SARS-CoV-2. A CDC spokesman, however, reported that experts have indicated that the cluster of deaths was not concerning. 

Health officials in Norway also reported in mid-January 2021 that they were investigating the deaths of 23 elderly individuals following vaccination with the Pfizer-BioNTech COVID-19 vaccine. The Norwegian Medicines Agency (NOMA) concluded that in 13 of the 23 deaths, common mRNA vaccine adverse reactions, such as diarrhea, fever, and nausea may have contributed to the deaths in the frail patients.  Deaths following the Pfizer-BioNTech COVID-19 vaccine have also been reported in Israel,  Germany,  Portugal  and Switzerland. 

In a presentation on COVID-19 vaccine safety made during the January 27, 2021 CDC’s Advisory Committee on Immunization Practices (ACIP) meeting, public health officials reported that through January 18, 2021, 50 cases of anaphylaxis following Pfizer-BioNTech COVID-19 vaccine had been confirmed using the Brighton Collaboration case definition criteria (Levels 1, 2, and 3 were considered cases). The median onset of symptoms occurred at 10 minutes (range from < 1 minute to 20 hours). Of these cases, 80 percent had reported a previous allergy history, and 24 percent had a previously documented history of anaphylaxis. Most cases of anaphylaxis occurred following the first vaccine dose. 

According to data collected through the federal Vaccine Adverse Events Reporting System (VAERS) through January 18, 2021, the most commonly reported adverse events  included headache, fatigue, dizziness, nausea, chills, fever, pain, injection site pain, extremity pain, and shortness of breath.  

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Pfizer - BioNTech COVID-19 Vaccine and Shingles

The Pfizer-BioNTech COVID-19 vaccines has been associated with shingles (herpes zoster – HZ) in persons with autoimmune inflammatory rheumatic diseases (AIIRD). A study published in the journal of Rheumatology in April 2021, found that: 

“The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: rheumatoid arthritis (n = 4), Sjogren’s syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in 5 cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects.”

Based on these findings, the study authors concluded that more research was needed to “clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster” in persons with AIIRD.

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Pfizer - BioNTech COVID-19 Vaccine and Graves Disease

Graves’ Disease, an autoimmune disorder affecting the thyroid, has also occurred after vaccination. A published study in May 2021 reported on two female health care workers who developed symptoms of Graves’ Disease three days post-vaccination with the Pfizer-BioNTech vaccine. Study authors noted that: 

“Vaccines have been shown to trigger an immune response that leads to a broad spectrum of autoimmune diseases, including autoimmune thyroid disease. Our patients met the diagnostic criteria for ASIA; they were exposed to an adjuvant (vaccine), and they developed clinical manifestations of thyroid hyperfunction within a few days, with the appearance of antithyroid antibodies, despite being healthy before vaccination.”

Based on their findings, the authors concluded that Graves’ Disease can occur following COVID-19 vaccination.

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Pfizer - BioNTech COVID-19 Vaccine in Adolescents

On May 10, 2021, the FDA expanded the EUA granted Pfizer/BioNTech to distribute its experimental mRNA vaccine in the U.S. to include administration to children as young as 12 years old  and the CDC’s ACIP voted to approve its use in this population on May 12, 2021. 

The approval for use in adolescents 12 to 15 years was based on a small clinical trial involving 2,260 teens, of which 1,131 received the vaccine and 1,129 received a saline placebo.  According to the FDA’s Fact Sheet for Healthcare Providers Administering Vaccine: 

"In a clinical study, adverse reactions in adolescents 12 through 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%)."

During the clinical trial, nearly 11 percent of 12- to 15-year-olds experienced a severe or Grade 3 vaccine reaction, with one study participant experiencing a Grade 4 reaction of a fever of 40.4°C. Five adolescents who received the Pfizer vaccine experienced a serious adverse event (SAE) during the trial, however, none of these events were considered by clinical trial investigators to be related to vaccination. 

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Pfizer - BioNTech COVID-19 Vaccine and VAERS Reports

According to data released October 8, 2021 by the CDC, reports received by VAERS for the Pfizer-BioNTech experimental COVID-19 vaccine totaled over 426,948 vaccine adverse events with 81,226 categorized as serious. Noted within these reports were 11,350 deaths; 17,699 permanent disabilities; 54,335 hospitalizations; 52,908 emergency room visits, and 12,143 life threatening events. Also noted in these reports were that 478 deaths reported were categorized as senior living administration, with 91 percent of overall reported deaths occurring in persons 65 years of age and older.

Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to VAERS, many doctors and other medical workers giving vaccines to children and adults fail to report vaccine-related health problem to VAERS. There is evidence to suggest that only between 1 and 10 percent of serious health problems that occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.       

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Moderna mRNA COVID-19 Vaccine

Moderna COVID-19 Vaccine Trial Data

On May 18, 2020, Moderna, Inc. of Cambridge, Massachusetts announced that it had obtained “positive interim clinical data” from a Phase 1 human clinical trial of its experimental mRNA-1273 COVID-19 vaccine.  However, four out of 45 healthy clinical trial participants experienced Grade 3 vaccine reactions. 

Each of the 45 participants was given two doses of the Moderna vaccine about a month apart at dosage levels that were either 25, 100 or 250 micrograms (µg). The mRNA-1273 vaccine reportedly produced a “Grade 3 adverse event” in one participant who received doses of between 25 µg and 100 µg. That individual experienced Grade 3 erythema (a rash) around the injection site. A Grade 3 rash can include blistering, open ulcers, wet peeling (moist desquamation) or a serious rash over large areas of the body. 

Three participants in the clinical trial who received a vaccine dose of 250 µg  experienced “Grade 3 systemic symptoms” following administration of the second dose. Moderna described these as the “most notable” of the adverse events and said that they had been “transient and self-resolving.”  

On July 27, 2020, the National Institutes of Health (NIH) announced that Phase 3 trials of Moderna’s mRNA-1273 had begun. According to the press release issued by NIH: 

“Trial volunteers will receive two intramuscular injections approximately 28 days apart. Participants will be randomly assigned 1:1 to receive either two 100 microgram (mcg) injections of mRNA-1273 or two shots of a saline placebo. The trial is blinded, so the investigators and the participants will not know who is assigned to which group.”

In September 2020, three participants involved in the Phase 3 trial reported suffering reactions such as high fever, headaches, body aches and exhaustion. One of these participants, 44-year-old Luke Hutchison of Utah, suffered a bad headache, chills, a fever (over 100°F), and shortness of breath after getting the second vaccine dose. Hutchison described his symptoms as “full-on COVID-like symptoms.” He cautioned that people receiving the vaccine should be made aware that serious adverse reactions can occur, especially after the second dose.  Another of the trial participants, a woman in her 50s from North Carolina, suffered a migraine that “left her exhausted and struggling to focus.” 

On November 16, 2020, Moderna reported that adverse reactions were generally mild or moderate, and included headache, fatigue, and injection site pain 

The FDA issued an EUA for Moderna’s COVID-19 vaccine on December 18, 2020. In its press release, the FDA reported that during clinical trials, common reactions following Moderna vaccination included injection site pain, headache, fatigue, joint and muscle pain, fever, nausea, vomiting, and swelling of the lymph nodes in the arm where the vaccine was given. Vaccine adverse events typically persisted for several days and were more common following the second dose of the two-dose series. 

Serious adverse events occurring at higher rates in the vaccine group included myocardial infarction, kidney stones, gall bladder inflammation and Bell’s Palsy. Seven serious adverse events occurred in the vaccine group following vaccination, with four considered by clinical trial investigators to be related to the vaccine. These included intractable nausea and vomiting, rheumatoid arthritis, and two incidents of facial swelling that occurred in persons who had previously received cosmetic injections of dermal fillers. 

Thirteen deaths were reported during the clinical trials, with six occurring in the vaccine group and seven in the placebo group. In the vaccine group, two individuals over the age of 75 years with a history of heart disease died of heart related complications, two individuals were found deceased at home and the exact cause was not determined (a 56-year-old with a history of hypertension and chronic back pain being treated with opioid medication died 37 days after dose 1 and a 70-year-old with a history of cardiac disease was found dead 57 days after dose 2). One vaccine recipient died of suicide 21 days after dose 1, and a 72-year-old vaccine recipient with a history of Crohn’s disease and short bowel syndrome who was hospitalized for acute kidney failure and thrombocytopenia developed complications resulting in multiorgan failure and death 40 days after dose 2.  

According to data collected through the Vaccine Adverse Events Reporting System (VAERS) through January 18, 2021, the most commonly reported adverse events  included headache, fever, chills, pain, dizziness, fatigue, nausea, injection site pain, extremity pain, and shortness of breath.  

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Moderna COVID-19 Vaccine and Anaphylaxis

In a presentation on COVID-19 vaccine safety made during the January 27, 2021 CDC’s Advisory Committee on Immunization Practices (ACIP) meeting, public health officials reported that through January 18, 2021, 21 cases of anaphylaxis following Moderna’s COVID-19 vaccine had been confirmed using the Brighton Collaboration case definition criteria (Levels 1, 2, and 3 were considered cases). The median onset of symptoms occurred at 10 minutes (range from < 1 minute to 45 minutes). Of these cases, 86 percent had reported a previous allergy history, and 24 percent had a previously documented history of anaphylaxis. Most cases of anaphylaxis occurred following the first vaccine dose and all cases of anaphylaxis occurred in females. 

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Moderna COVID-19 Vaccine and Deaths Post Vaccination

A cluster of deaths occurring within a week of Moderna COVID-19 vaccination at a nursing home in Arkansas was reported to VAERS in early January 2021. All four seniors who passed away following vaccination were found to be positive for SARS-CoV-2. The deaths, however, were reported as being related to COVID-19, and not the vaccine.   

Also in January, baseball Hall of Famer Hank Aaron was administered the Moderna vaccine in an event that appeared to encourage others, especially African-Americans, to receive the vaccine. Seventeen days later, on January 22, 2021, Aaron died. Health officials have denied that the COVID-19 vaccine played a role in his death, and report that it was purely coincidental. 

According to the federal vaccine adverse event reporting system (VAERS), as of CDC’s October 8, 2021 release of data there were a total of 309,258 reports submitted to VAERS associated with the experimental Moderna COVID-19 vaccine. Noted within these reports were 27,959 serious events including 4,144 deaths; 5,498 permanent disabilities; 19,514 hospitalizations; 7,911 emergency room visits; and 4,585 life threatening events. Of the deaths reported to VAERS, 463 were noted as senior living administration settings, with over 91 percent of overall reported deaths occurring in persons 65 years of age and older.

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Moderna COVID-19 Vaccine and Heart Inflammation

On October 8, 2021, Iceland halted the use of the Moderna COVID-19 mRNA vaccine following increasing rates of heart inflammation. According to Iceland’s Directorate of Health: 

“In recent days, there has been data from the Nordic countries on the increased incidence of myocarditis and pericarditis after vaccination with Moderna vaccine in addition to vaccination with Pfizer/ BioNTeck (Comirnaty)…As there is a sufficient supply of Pfizer vaccine in Iceland for both the pre-vaccine activation vaccines and the primary vaccinations of those who have not yet been vaccinated, the epidemiologist has decided not to use the Moderna vaccine in Iceland, while providing further information on the safety of the Moderna vaccine.”

As of October 6, 2021, Sweden and Denmark restricted the use of the Moderna vaccine to persons born prior to 1991 due to heart inflammation in younger populations, especially following the second dose. Finland stopped use of the vaccine in men under age 30 on October 7, 2021 due to the risk of heart inflammation in this population. 

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Adverse Events Following mRNA COVID-19 Vaccine Administration

Health officials have cautioned that symptoms of adverse reactions following COVID-19 vaccination may overlap with those of COVID-19 illness and be difficult to distinguish. However, symptoms of loss of taste or smell, shortness of breath, cough, rhinorrhea or sore throat are not considered common vaccine reactions, and persons experiencing these symptoms post-vaccination may be positive for SARS-CoV-2 or another infection. 

Persons who have pre-existing immunity to SARS-CoV-2 may be at increased risk of severe reactogenicity following mRNA COVID-19 vaccination. In a study pending peer review conducted by the Icahn School of Medicine at Mount Sinai, researchers reported that persons with pre-existing immunity to SARS-CoV-2 who received mRNA COVID-19 vaccines had significantly higher rates of systemic reactions when compared to those who were not immune at the time of vaccination. Systemic reactions included fatigue, headache, chills, fever, joint or muscle pains. 

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COVID-19 mRNA Vaccines and Blood Clots

Thrombocytopenia, a serious blood disorder that causes low platelets which will prevent the blood from clotting, has been reported following mRNA vaccination.  In some cases, death has resulted from the bleeding disorder.  In one case, a 56-year-old obstetrician who developed the condition within three days of receiving the Pfizer-BioNTech COVID-19 vaccine died of a stroke 16 days post-vaccination.  Thrombocytopenia with thrombosis syndrome (TTS), a serious and potentially fatal blood clotting disorder linked to the Janssen/Johnson & Johnson and AstraZeneca COVID-19 vaccines, has also been reported following mRNA vaccination. In late June 2021, the Annals of Internal Medicine published a case report on a fatal case of TTS following the completion of the Moderna two doses vaccine series. 

On May 7, 2021, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) reported that they were monitoring a potential risk of blood clots with low platelets in persons who have received the Pfizer-BioNTech and Moderna COVID-19 vaccines. The committee acknowledged that cases of this serious side effect had been reported following mRNA vaccination but the numbers were considered extremely low. 

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COVID-19 mRNA Vaccines and Heart Inflammation

Additionally, PRAC reported that cases of pericarditis (inflammation of the membrane surrounding the heart) and myocarditis (inflammation of the heart muscle) following mRNA vaccination, primarily in persons who have received the Pfizer-BioNTech vaccine had been reported.  

In late April 2021, the Israeli Health Ministry reported that it was investigating a link between the Pfizer COVID-19 vaccine and myocarditis after reporting that 62 cases had been reported following vaccination. Of these cases, 56 had occurred following the second shot, and most had involved persons 30 years of age and younger. A Pfizer spokesperson, however, has stated that a causal link has not been established and that they have not observed a higher rate of myocarditis post-vaccination then what would be expected in the overall population. 

On May 17, 2021, the Advisory Committee on Immunization Practices (ACIP) COVID-19 Vaccine Safety Technical (VaST) Work Group met and reviewed information on myocarditis following mRNA vaccines. VaST reported that most of the cases had occurred in teens and young adults, and more cases had occurred in males. Additionally, there were more cases reported after the second vaccine dose, and most occurred on average within four days of vaccination. Members of VaST reported that few cases had been reported but that information on myocarditis following COVID-19 vaccination should be given to vaccine providers. 

Reports of myocarditis and pericarditis following mRNA vaccines continued to increase and on June 11, 2021, the CDC scheduled an emergency ACIP meeting for June 18, 2021 to discuss the higher than expected number of cases. A total of 301 cases following Moderna vaccination and 488 cases following Pfizer vaccination had been reported at the time the meeting was scheduled. 

The meeting, however, was postponed due to the newly created Juneteenth National Independence Day holiday, with the CDC announcing that it would discuss concerns the following week at the regularly scheduled June ACIP meeting.  By the June 23, 2021 meeting, CDC officials reported that through June 11, 2021, 1,226 cases of myocarditis/pericarditis had been reported to VAERS, with 791 occurring after Pfizer vaccination and 435 after Moderna vaccination. Most cases were reported in males, and most occurred following the second dose. 

In the data presented during the June 23, 2021, the CDC reported that in females between the age of 12 and 17 years, after the second dose, the case rate of myocarditis/ pericarditis was 9.1 per million doses administered. In males 12 to 17 years of age, however, the rate after the second vaccine dose was 66.7 per million doses. Cases among females 18 to 24 years old after the second dose were reported at 5.5 per million, while after the second dose, males of the same age range were affected at a rate of 56.3 per million doses. Most cases of myocarditis/pericarditis resulted in hospitalization, and while most were reported as being resolved, the long-term health outcomes were reported to be unknown.    

The CDC, however, declined to pause use or make changes to the vaccine recommendations, as they reported the benefits to vaccination outweighed the risk. Additionally, they stated that persons with a history of myocarditis and pericarditis could still receive an mRNA vaccine and persons who developed pericarditis after the first mRNA vaccine dose could receive the second dose after symptoms resolved. The CDC also advised that individuals who developed myocarditis after the first dose could consider receiving a second dose under certain circumstances. No data to support this recommendation was provided. 

The FDA reported that the Moderna and Pfizer Fact Sheets would be updated to include a warning of the risk of myocarditis/pericarditis. 

A study of myocarditis after mRNA vaccines on members of the military has found a higher than expected number of cases following vaccination.  Additional studies have also associated mRNA vaccines with heart inflammation, with researchers reporting the need for further investigation. 

A real-world study on the Pfizer-BioNTech vaccine conducted by Israeli scientists found that vaccination most likely caused myocarditis in one to five individuals per 100,000 who would not have developed the condition. Their study also found that young males were at highest risk for developing the condition. 

A preprint study posted on September 8, 2021 on MedRxiv found that teenage boys are most likely to be hospitalized for heart inflammation from mRNA COVID-19 vaccines than from COVID-19 disease. This study was based on filed reports to the Vaccine Adverse Events Reporting System (VAERS) between January 1 and June 18, 2021 in teens between the ages of 12 and 17 years of age. Researchers concluded that: 

“For boys with no underlying health conditions, the chance of either cardiac adverse event (CAE), or hospitalization for CAE, after their second dose of mRNA vaccination are considerably higher than their 120-day risk of COVID-19 hospitalization, even at times of peak disease prevalence. The long-term consequences of this vaccine-associated cardiac inflammation are not yet fully defined and should be studied.”

Study authors suggested that the U.S. could consider a policy change that would delay vaccination in healthy children who have a low risk of developing severe COVID-19 illness or recommend only a single vaccine dose of mRNA vaccine. 

According to the CDC, as of October 6, 2021, 1,640 reports of myocarditis and pericarditis following COVID-19 mRNA vaccines had been reported to VAERS among persons 30 years of age and younger. Most cases have occurred in teenage boys. 

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COVID-19 mRNA Vaccines and Kidney Disorders

On August 11, 2021, the European Medicines Agency (EMA) announced that it was investigating a link between two kidney disorders, glomerulonephritis and nephrotic syndrome, and mRNA COVID-19 vaccines. 

Glomerulonephritis is a condition where inflammation of the glomeruli of the kidneys occur. Glomeruli filter excess waste, fluid, and electrolytes from bloodstream and move them into the urine. This condition can lead to kidney damage.    

Nephrotic syndrome occurs when damage of the small blood vessels in the kidney that filter excess water and waste happens. Nephrotic syndrome generally causes swelling, frequently in the feet and ankles, and may increase a person’s risk of blood clots and infection.    

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COVID-19 mRNA Vaccines and Skin Allergy

Erythema multiforme, an allergic skin reaction characterized by red, raised, symmetrical areas over the entire body, has been linked to COVID-19 mRNA vaccines. On August 11, 2021, the EMA reported that it was investigating reports of this immune-mediated reaction following mRNA vaccination. This reaction can cause fever, joint pain, itching, and cold sores.  

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COVID-19 mRNA Vaccines and Central Nervous System (CNS) Demyelination

A case series published in the Journal of Neurology has linked both the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines to Central Nervous System (CNS) Demyelination, including multiple sclerosis (MS). The published case series reported on four cases of exacerbation of their stable MS, two new cases of MS following vaccination, and one case of neuromyelitis optica. Three of these events occurred following Moderna COVID-19 vaccination, while four occurred after Pfizer-BioNTech COVID-19 vaccination. 

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COVID-19 Vaccines and Multisystem Inflammatory Syndrome

In early September 2021, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) reported that it was assessing a potential link between COVID-19 vaccines and Multisystem Inflammatory Syndrome (MIS) following the report of a 17-year-old male who developed the condition following receipt of the Comirnaty (Pfizer-BioNTech) mRNA vaccine. The committee also reported that five cases of MIS had been reported in Europe following Pfizer vaccination, and one case had been reported following vaccination with both the Moderna and Johnson & Johnson/Janssen vaccines. 

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Impact of COVID-19 mRNA Vaccination of Placebo Group to Long-Term Clinical Trial Data

Long-term follow-up of clinical trial participants to monitor for conditions such as cancer and autoimmune diseases will become difficult, if not impossible, if the vaccine makers hasten to offer their vaccines to the placebo groups. Once this occurs, it will completely erase the ability of researchers to compare or evaluate potential long-term differences in health outcomes among the vaccinated and placebo groups. Pfizer and Moderna company executives both suggested that the COVID-19 vaccine clinical trial participants who received a placebo should be vaccinated. 

In December 2020, Pfizer-BioNTech officials stated that they would begin offering the vaccine to placebo recipients by March 1, 2021, which was several months earlier than what they had originally planned for.  By mid- January 2021, Moderna had already begun offering the vaccine to some placebo group participants. 

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Janssen/Johnson & Johnson COVID-19 Vaccine

Janssen/Johnson & Johnson COVID-19 Vaccine Trial Data

In late September 2020, Janssen/Johnson & Johnson released results of the Phase 1/2a clinical trial for its Ad26.COV2.S vaccine. This study was a double-blind, randomized, placebo-controlled trial and included 796 participants divided into two groups consisting of 402 healthy adults 18 to 55 years of age in one group and 394 healthy elderly individuals 65 years of age and older in the other.

In this trial, the first group was broken out into cohort 1a and cohort 1b. The second group was cohort 3. Trial participants were administered a single intramuscular injection of Ad26.COV2.S at dose levels of either 5×1010 or 1×1011 viral particles (vp) per dose of vaccine.   

Approximately 58 percent of participants in cohorts 1a and 1b experienced a localized adverse event, while 64 percent of them also suffered systemic adverse events. Of the participants in cohort 3, 27 percent of them experienced a localized adverse event, and 36 percent suffered systemic events (e.g. fever, irritability, drowsiness, rash, etc.) Of healthy adults aged 18 to 55 years old in cohorts 1a and 1b, 19 percent came down with fevers, while four percent of the adults aged over 65 years old in cohort 3 developed fevers.    

The fevers reported by participants were considered mild or moderate and resolved within one to two days after vaccination. However, five percent (20 participants) of participants in cohorts 1a and 1b suffered from Grade 3 fevers of over 101.3°F.

A news report on the Janssen/Johnson & Johnson Phase 1/2a trial reported that

“There were two severe adverse events recorded. One participant had hypotension; however, this effect is not related to vaccination as the participant had a history of hypotension. Another participant with fever was hospitalized as a suspected case of COVID-19; however, the fever resolved within 12 hours.” 

The most common adverse events experienced by trial participants were headaches, muscle pain, fatigue and pain the injection site.    

On September 23, 2020, Janssen/Johnson & Johnson announced the start of its Phase 3 clinical trials. The trial, a randomized, double-blind, placebo-controlled study, would enroll up to 60,000 participants in three continents.  However, on October 12, 2020, all clinical trials stopped after a participant developed an “unexplained illness.”   Sources familiar with the event reported that a male in his 20’s had a stroke after receiving the experimental vaccine.  Clinical trials in the U.S  resumed in late October 2020. 

On February 27, 2021, the FDA issued an EUA for Janssen/Johnson & Johnson’s experimental vaccine for use in persons 18 years of age and older. 

Common side effects reported after vaccine administration with the Janssen COVID-19 in clinical trials included injection site pain, headache, fatigue, myalgia, nausea, fever, injection site redness and swelling. 

According to the Fact Sheet for Healthcare Providers issued by the FDA, serious adverse effects (SAE) were reported in 0.4 percent of vaccine recipients and 0.4 percent of placebo recipients. The Fact Sheet reports:  

“Urticaria (all non-serious) was reported in five vaccinated individuals and 1 individual who received placebo in the 7 days following vaccination. In addition, an SAE of hypersensitivity, not classified as anaphylaxis, was reported in 1 vaccinated individual with urticaria beginning two days following vaccination and angioedema of the lips with no respiratory distress beginning four days following vaccination. The event was likely related to the vaccine.

An SAE of severe pain in the injected arm, not responsive to analgesics, with immediate onset at time of vaccination, and that was ongoing 74 days following vaccination was reported in an individual who received the Janssen COVID-19 Vaccine. An SAE of severe generalized weakness, fever, and headache, with onset on the day following vaccination and resolution three days following vaccination was reported in an individual who received the Janssen COVID-19 Vaccine. Both SAEs are likely related to the vaccine.

Numerical imbalances, with more events in vaccine than placebo recipients, were observed for the following serious and other adverse events of interest in individuals receiving the vaccine or placebo, respectively:

  • Thromboembolic events: • Deep vein thrombosis: 6 events (2 serious; 5 within 28 days of vaccination) vs. 2 events (1 serious; 2 within 28 days of vaccination).
  • Pulmonary embolism: 4 events (3 serious; 2 within 28 days of vaccination) vs. 1 event (serious and within 28 days of vaccination).
  • Transverse sinus thrombosis: 1 event (serious and within 28 days of vaccination) vs. 0.
  • Seizures: 4 events (1 serious; 4 within 28 days of vaccination) vs. 1 event (0 serious and 0 within 28 days following vaccination).
  • Tinnitus: 6 events (0 serious; 6 within 28 days of vaccination, including 3 within 2 days of vaccination) vs. 0.”

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Janssen/Johnson & Johnson COVID-19 Vaccine and Blood Clots

On April 13, 2021, the FDA and CDC paused use of the vaccine after serious blood clots were reported in women between the ages of 18 and 49.  By April 23, 2021, 15 cases and 3 deaths had been associated with the rare blood clot disorder, now referred to by health officials as thrombosis with thrombocytopenia syndrome (TTS). All cases were reported in women, with two occurring in women over 50 years of age. The CDC’s Advisory Committee on Immunization Practices (ACIP) voted to resume full use of the vaccine in all persons 18 years of age and older on April 23, 2021, by a vote of 10 to 4 (with one voting member abstaining due to a conflict of interest). Those who voted against the recommendation expressed concern regarding the lack of warning on the risk of TTS in women under 50 years of age.   

The FDA updated the Janssen/Johnson & Johnson’s COVID-19 Fact Sheet on April 23, 2021 and acknowledged that: 

“Reports of adverse events following use of the Janssen COVID-19 Vaccine under emergency use authorization suggest an increased risk of thrombosis involving the cerebral venous sinuses and other sites (including but not limited to the large blood vessels of the abdomen and the veins of the lower extremities) combined with thrombocytopenia and with onset of symptoms approximately one to two weeks after vaccination. Most cases of thrombosis with thrombocytopenia reported following the Janssen COVID-19 Vaccine have occurred in females ages 18 through 49 years; some have been fatal. The clinical course of these events shares features with autoimmune heparin-induced thrombocytopenia. In individuals with suspected thrombosis with thrombocytopenia following the Janssen COVID-19 Vaccine, the use of heparin may be harmful and alternative treatments may be needed. Consultation with hematology specialists is strongly recommended.”

By May 7, 2021, there had been 28 cases of TTS and 3 deaths confirmed by the CDC to be related to the Johnson & Johnson/Janssen COVID-19 vaccine. Additionally, TTS has been reported in men and in women between 50 and 60, in addition to women between 18 and 49 years. 

As of October 6, 2021, 47 cases of TTS following the Janssen/Johnson & Johnson COVID-19 vaccine had been confirmed by the CDC and FDA. 

In early September 2021, the European Medicines Agency reported that its Pharmacovigilance Risk Assessment Committee (PRAC) was investigating a link between the Johnson & Johnson/Janssen COVID-19 vaccine and venous thromboembolism (blood clots in the veins). According to PRAC, in the initial clinical trials of the vaccine, a higher rate of venous thromboembolism was noted in the vaccine group when compared to the placebo group. Additional data collected from two larger clinical trials were expected to be submitted to PRAC in advance of vaccine marketing authorization, to determine whether the condition was linked to vaccination.   

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Janssen/Johnson & Johnson COVID-19 Vaccine and Guillain-Barré Syndrome (GBS)

On July 13, 2021, the FDA announced revisions to the Fact Sheet for Healthcare Providers Administering the Johnson & Johnson/Janssen COVID-19 vaccine and the Fact Sheet for Recipients and Caregivers to include information regarding an increased risk of Guillain-Barré Syndrome (GBS) following vaccination. GBS, a serious neurological disorder where the body’s immune system attacks the peripheral nervous system, can cause muscle weakness, paralysis, and even death. According to the press release, the FDA reported 100 cases of GBS following vaccination, with 95 considered serious and requiring hospitalization, and one death. Government health officials noted that there was insufficient evidence to establish a causal relationship between the Johnson & Johnson/Janssen COVID-19 vaccine and GBS, and reported that “the known and potential benefits clearly outweigh the known and potential risks.” 

As of October 6, 2021, 228 cases of GBS following the Janssen/Johnson & Johnson COVID-19 had been identified in the VAERS data. According to the CDC, most cases occurred within 2 weeks of vaccination and among men, primarily those aged 50 and older. 

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Janssen/Johnson & Johnson COVID-19 Vaccine and VAERS Reports

As of the October 8, 2021 data release, vaccine adverse events submitted to VAERS associated with the Johnson & Johnson/Janssen COVID-19 vaccine totaled 61,939, with 7,982 noted as serious. Included in these reports were 1,228 deaths; 1,574 permanent disabilities; 7,948 emergency room visits, and 5,659 hospitalizations.

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Countermeasures Injuries Compensation Program Data

On Mar. 10, 2020, the Secretary of Health and Human Services (HHS) invoked the 2005 Public Readiness and Emergency Preparedness (PREP) Act, after declaring that the COVID-19 pandemic was a public health emergency. As a result, manufacturers of COVID-19 vaccines that have been developed to respond to the SARS-CoV-2 pandemic are considered public health emergency “countermeasures”. The PREP Act shields manufacturers and vaccine providers from liability and vaccine injury compensation claims will be processed by the Countermeasures Injury Compensation Program (CICP).     

All COVID-19 vaccines, including the licensed Pfizer mRNA COVID-19 vaccine, are considered countermeasures. Persons harmed or who die as a result of vaccination may file for benefits through the CICP within one year of injury or death of a loved one. 

As of October 1, 2021, HRSA reports that 1,357 claims alleging injury or death following COVID-19 vaccines have been filed with the CICP. Additionally, 1,801 claims alleging injury or death following additional COVID-19 countermeasures (i.e. medications, treatments, testing) have also been filled. HRSA also reports that no COVID-19 CICP claims have been compensated, and 3 claims have been denied because the standard of proof for causation was not met and/or a covered injury was not sustained. One COVID-19 claim has been determined eligible for compensation and is pending a review of eligible expenses.” 

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IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Updated October 20, 2021

 

Who is at highest risk for complications from the COVID-19 vaccine?

vaccine complications

Outstanding Safety Concerns

Paradoxical Immune Enhancement (Disease Enhancement)

For the past two decades, coronavirus vaccine research has been hampered by one consistent adverse outcome in particular - paradoxical immune enhancement or disease enhancement. This occurs because coronaviruses produce two different types of antibodies—neutralizing antibodies that fight the infection, and binding antibodies (or  non-neutralizing antibodies) that cannot prevent viral infection. Incapable of preventing viral infection, binding antibodies can instead trigger paradoxical immune enhancement.  This means that a person may seem fine until they contract the illness, and when this occurs, the disease is much more severe than it would have otherwise been.   

In the FDA briefings issued at the December 2020 Vaccines and Related Biological Products Advisory Committee (VRBPAC) meetings for both the Pfizer-BioNTech and Moderna COVID-19 vaccines, the agency reported that:   

“Available data do not indicate a risk of vaccine-enhanced disease, and conversely suggest effectiveness against severe disease within the available follow-up period. However, risk of vaccine-enhanced disease over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further in ongoing clinical trials and in observational studies that could be conducted following authorization and/or licensure.”

This information was also included in the Janssen/Johnson & Johnson FDA briefing document presented at the February 26, 2021 VRBPAC meeting in advance of the emergency use authorization approval. 

 

Increased HIV infection risk

COVID-19 vaccines that use a recombinant adenovirus type-5 (Ad5) vector may increase the risk of HIV infection in males. In 2007, researchers testing an experimental HIV vaccine using an Ad5 vector to introduce HIV surface proteins into the body discovered that uncircumcised males who had been previously exposed naturally to adenovirus type-5 prior to receiving the experimental HIV vaccine were at an increased risk for developing HIV infection. 

Researchers have expressed concern that the use of any potential COVID-19 vaccine using an Ad5 vector may increase the risk of HIV infection and caution its use among populations vulnerable to the disease. 

Vaccine candidates that use Ad5 vectors include China-based CanSino Biologics COVID-19 vaccine and Russia’s Gamaleya Research Institute’s Sputnik V COVID-19 vaccine. Both experimental vaccines are involved in ongoing large-scale clinical trials globally.  On February 12, 2021, Hungary drug regulators approved the Sputnik vaccine through an emergency use authorization even though the vaccine had not yet been approved by the European Medicines Agency (EMA).  Pakistan has approved both the CanSino and the Sputnik V COVID-19 vaccines for emergency use. 

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COVID-19 Vaccines and high-risk populations

Early COVID-19 vaccine clinical trials nearly exclusively enrolled healthy adults between the ages of 18 and 55 years. Few studies involve persons over the age of 65, or those with pre-existing health conditions.  As clinical trials expand, health status and age of trial participants and trial outcomes in at risk populations merit evaluation against any government use recommendations made for COVID-19 vaccines.

The Centers for Disease Control and Prevention (CDC) prioritized persons living in long-term care facilities (LTCF) in the initial phase of COVID-19 vaccine allocation even though this population was not studied in clinical trials. Vaccine safety and efficacy data on the use of COVID-19 vaccines in persons residing in LTCF remains unknown. The media have reported on deaths following vaccination in this population, however, public health officials have quickly dismissed any link to the COVID-19 vaccines.       

On July 2, 2021, the CDC acknowledged that no safety and efficacy data existed on the use of COVID-19 vaccines in persons with autoimmune disorders; in persons who are immunocompromised; and that data is insufficient relating to timing of vaccine for those  who take medications that may lead to immunocompromised. The CDC, however, stated that persons with these conditions could still be vaccinated if they did not have a contraindication to vaccination.  In their guidance documents updated on September 15, 2021, the CDC reported that “the currently FDA-approved or FDA-authorized COVID-19 vaccines are not live vaccines and therefore can be safely administered to immunocompromised people.” 

No data was offered by the CDC to support the safety of COVID-19 vaccination within this population. The CDC, however, reported that studies had found a decreased immune response following administration of a 2-dose mRNA COVID-19 vaccine series in persons with certain immunosuppressive conditions. As a result of these findings, the CDC has stated that a third mRNA COVID-19 vaccine dose should be considered in the population. While small studies report an enhancement of antibody response following use of a third dose, health officials note that the benefits of additional vaccine doses were not known. The CDC also reports that the reactogenicity of a third dose was similar to previous vaccine doses.  

Cases of Bell’s palsy following COVID-19 vaccination were also reported during clinical trials. Health officials report that data is insufficient to conclude that a causal relationship exists between the cases and vaccination. They have, however, despite the absence of data, opted to recommend COVID-19 vaccination in persons with a history of Bell’s palsy. 

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COVID-19 Vaccines and Children

At the October 22, 2020 FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting on COVID-19 vaccine safety and efficacy, some committee members expressed that bridging data between adult and pediatric populations might not be advisable due to concerns which included differing immune responses between the populations as well as the potential risk of Multisystem Inflammatory Syndrome in Children (MIS-C). 

MIS-C is a condition where various organs of the body become inflamed and can include the heart, lungs, kidneys, skin, brain, gastrointestinal system, or eyes. Symptoms of the syndrome can include neck pain, rash, diarrhea, vomiting, red eyes, excessive fatigue, and abdominal pain. The CDC reports that they do not know what causes this condition, but that many children who develop it have a personal health history of exposure to the SARS-CoV-2 virus or have been in contact with an infected individual. 

In early September 2021, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) reported that it was assessing a potential link between COVID-19 vaccines and MIS following the report of a 17-year-old male who developed the condition following receipt of the Comirnaty (Pfizer-BioNTech) mRNA vaccine. The committee also reported that five cases of MIS had been reported in Europe following Pfizer vaccination, and one case had been reported following vaccination with both the Moderna and Johnson & Johnson/Janssen vaccines. 

On October 14, 2020, Pfizer-BioNTech announced it had received approval by the U.S. Food and Drug Administration (FDA) to enroll children in the Phase 3 human clinical trial of its experimental mRNA COVID-19 vaccine. The trial was expanded to include adolescents as young as 16 years old with person who have chronic health conditions such as hepatitis B, hepatitis C, and HIV. 

When the FDA approved use of the Pfizer-BioNTech vaccine in persons as young as 16 years of age, the approval was based on data collected from only 153 adolescents aged 16 and 17- years, of which 77 received the vaccine, and 76 received the placebo. 

In mid-January 2021, Pfizer-BioNTech announced that clinical trials involving 12 to 15-year-old children were fully enrolled with 2,259 children participating.  According to a press release issued by the company on March 31, 2021, the vaccine was reported to be 100 percent effective in this population, based on a study of 2,260 adolescents 12 to 15 years of age.  On April 9, 2021, company officials announced that they had submitted a request to the FDA for approval of the vaccine for use in this population. 

The FDA authorized use of the Pfizer-BioNTech COVID-19 vaccine in adolescents 12 to 15 years of age on May 10, 2021.  Two days later, on May 12, 2021, the CDC’s ACIP voted to recommend its use for all persons 12 years and older. 

Clinical trials involved 2260 adolescents, 1131 who received the vaccine, and 1129 who received a saline placebo. According to the FDA’s Fact Sheet for Healthcare Providers Administering Vaccine: 

“In a clinical study, adverse reactions in adolescents 12 through 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%).”

ACIP also reported that during the clinical trial, nearly 11 percent of 12- to 15-year-olds experienced a severe or Grade 3 vaccine reaction, with one study participant experiencing a Grade 4 reaction of a fever of 40.4°C. Five adolescents who received the Pfizer vaccine experienced a serious adverse event (SAE) during the trial, however, none of these events were considered by clinical trial investigators to be related to vaccination. 

In late March 2021, phase 1/2/3 clinical trials of the Pfizer-BioNTech vaccine in infants and children 6 months to 11 years of age were initiated. According to the press release issued on March 31, 2021, “the study is evaluating the safety, tolerability, and immunogenicity of the Pfizer-BioNTech COVID-19 vaccine on a two-dose schedule (approximately 21 days apart) in three age groups: children aged 5 to 11 years, 2 to 5 years, and 6 months to 2 years.”      

On September 28, 2021, Pfizer announced that it had submitted Phase 2/3 data to the FDA to support the use of a lower dose COVID-19 mRNA vaccine in children 5 through 11 years of age.  Authorization of a 10 μg dose of the vaccine through EUA is anticipated by the end of October. 

Phase 2/3 clinical trials of the Moderna COVID-19 mRNA vaccine in children and adolescents ages 12 to 17 years are also underway. Clinical trials must involve a minimum of 3,000 adolescent trial participants to provide efficacy and safety data, and receive FDA approval for use in this population. As of October 1, 2021, the Moderna COVID-19 vaccine is only permitted for use in persons 18 years and older. 

On March 16, 2021, Moderna announced that Phase 2/3 clinical trials had begun in infants and children ages 6 months through 11 years of age. According to company officials, clinical trials would “evaluate the safety, tolerability, reactogenicity and effectiveness of two doses of mRNA-1273 given 28 days apart” and involve approximately 6,750 U.S. and Canadian children between 6 months and less than 12 years of age. 

Moderna has stated that they expect to submit data to the FDA on the use of their COVID-19 vaccine in children ages 6 through 11 by the end of 2021. 

On February 26, 2021, Janssen/Johnson & Johnson announced plans to enroll approximately 3,000 children ages 12 to 18 in a study to evaluate use of its product in this population. 

The University of Oxford also announced in mid-February 2021 that it would begin testing its COVID-19 vaccine developed with pharmaceutical giant AstraZeneca on children aged 6 to 17 years.  The pediatric trials, however, were halted in early April 2021, due to vaccine associated blood clots in adults. No blood clots had been reported among clinical trial participants, however, the University of Oxford stopped use of the vaccine in children and adolescents until more data becomes available. 

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COVID-19 Vaccines in Pregnant and Lactating Women

There is little safety data available on the use of COVID-19 vaccines or mRNA vaccines in pregnant women and only limited data available from animal development and reproductive toxicity studies. The potential risk of these vaccines to pregnant women and the developing infant has not been fully studied and remains unknown. There is also no safety data on the use of COVID-19 vaccines in lactating women. Information is lacking on the effects of mRNA or COVID-19 vaccines in the breastfed infant, or on milk production or excretion.       

Without safety data to support the use of COVID-19 vaccines in pregnant women, the American College of Obstetricians and Gynecologists (ACOG) requested that pregnant and/or lactating women be included in a high priority population with regards to the COVID-19 vaccine allocation plan. 

Public comments submitted by ACOG to the CDC’s Advisory Committee on Immunization Practices on October 27, 2020 requested that:  

“Should an Emergency Use Authorization be executed for one or more COVID-19 vaccines and provide a permissive recommendation for pregnant and lactating women, pregnant health care workers, pregnant first responders, and pregnant individuals with underlying conditions should be prioritized for vaccination alongside their non-pregnant peers.”

On February 18, 2021, Pfizer announced that it had begun a global Phase 2/3 study of its COVID-19 vaccine in pregnant women 18 years of age and older. The company stated that the trial would enroll 4,000 healthy pregnant women and vaccinate them between 24-34 weeks gestation. According to Pfizer’s press release: 

“The study will evaluate the safety, tolerability, and immunogenicity of two doses of BNT162b2 or placebo administered 21 days apart. Each woman will participate in the study for approximately 7 to 10 months, depending on whether she was randomized to receive the vaccine or placebo. The study will assess safety in infants of vaccinated pregnant women and the transfer of potentially protective antibody to their infants. Infants will be monitored through approximately six months of age. As established in the study protocol, after a participant’s infant is born, maternal trial participants will be unblinded and those who were in the placebo group will receive the vaccine.”

During a virtual briefing held on April 23, 2021, CDC Director Dr. Rochelle Walensky recommended that pregnant women receive a COVID-19 vaccine.  This recommendation was made following the release of a CDC observational study published in the New England Journal of Medicine that reported data on 35,691 v-safe participants between 16 to 54 years of age who identified themselves as pregnant and concluded that: 

“Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.”

3,958 women answered questions from the v-safe registry call center, and of these reports, nearly 98 percent reported that they had not developed COVID-19 infection, while 56 women reported COVID-19 infection prior to vaccination, and 22 women developed the illness following vaccination. Of the 827 women who completed their pregnancies, live births were reported in 712, while “spontaneous abortions” were the most frequently reported outcome in the remaining cases. One stillbirth was reported, and adverse outcomes included 60 cases of premature births, 23 cases of small size related to gestational age, and 16 cases reported significant congenital abnormalities. 

Study limitations included the passive nature of the vaccine adverse reporting system, the fact that most women who noted themselves as being pregnant did not answer questions, and the lack of data on the total number of COVID-19 vaccine doses given to pregnant women. Researchers also noted that: 

“Continued monitoring is needed to further assess maternal, pregnancy, neonatal, and childhood outcomes associated with maternal Covid-19 vaccination, including in earlier stages of pregnancy and during the preconception period. Meanwhile, the present data can help inform decision making about vaccination by pregnant persons and their health care providers.”

On September 29, 2021, the CDC issued a Health Alert Network Advisory urging pregnant women to receive the COVID-19 vaccine. In their alert, the CDC stated that they were recommending COVID-19 vaccination in women who were pregnant, nursing, and in those who were planning on becoming pregnant “because the benefits of vaccination outweigh known or potential risks.”

The CDC reported that while the absolute risk of COVID-19 disease in pregnant women is low, those who develop symptomatic illness were twice as likely to be hospitalized in the Intensive Care Unit (ICU), require mechanical ventilation, and 70 percent more likely to die. Additionally, the CDC acknowledged that transmission of the SARS-CoV-2 virus between mother and infant was exceedingly rare, occurring at a rate of 1 to 4 percent  using rRT-PCR tests. However, rRT-PCR tests can only confirm presence of virus and not whether or not an individual is infectious – see Testing Controversy.  According to statements by the CDC in September 2021, 31 percent of pregnant women were reported to be fully vaccinated, a rate lower than that of the general population. 

Heart inflammation following mRNA vaccination

Children and young adults who receive an mRNA vaccine are at an increased risk for myocarditis/pericarditis. In mid-May 2021, the CDC’s Vaccine Safety Technical (VaST) work group reported that an increasing number of cases of the serious heart complication were being reported to VAERS. VaST reported that most of the cases had occurred in teens and young adults, and more cases had occurred in males. Additionally, there were more cases reported after the second vaccine dose, and most occurred on average within four days of vaccination. 

By the June 23, 2021 ACIP meeting, CDC officials reported that through June 11, 2021, 1,226 cases of myocarditis/pericarditis had been reported to VAERS, with 791 occurring after Pfizer vaccination and 435 after Moderna vaccination. Most cases were reported in males, and most occurred following the second dose. 

In the data presented during the June 23, 2021, the CDC reported that in females between the age of 12 and 17 years, after the second dose, the case rate of myocarditis/ pericarditis was 9.1 per million doses administered. In males 12 to 17 years of age, however, the rate after the second vaccine dose was 66.7 per million doses. Cases among females 18 to 24 years old after the second dose were reported at 5.5 per million, while after dose two, males of the same age range were affected at a rate of 56.3 per million doses. Most cases of myocarditis/pericarditis resulted in hospitalization, and while most were reported as being resolved, the long-term health outcomes were reported to be unknown.  

The CDC, however, declined to pause use or make changes to the vaccine recommendations, as they reported the benefits to vaccination outweighed the risk. Additionally, they stated that persons with a history of myocarditis and pericarditis could still receive an mRNA vaccine and persons who developed pericarditis after the first mRNA vaccine dose could receive the second dose after symptoms resolved. The CDC also advised that individuals who developed myocarditis after the first dose could consider receiving a second dose under certain circumstances. No data to support this recommendation was provided. 

The FDA reported that the Moderna and Pfizer Fact Sheets would be updated to include a warning of the risk of myocarditis/pericarditis. 

A study of myocarditis after mRNA vaccines on members of the military has found a higher than expected number of cases following vaccination.  Additional studies have also associated mRNA vaccines with heart inflammation, with researchers reporting the need for further investigation. 

A real-world study on the Pfizer-BioNTech vaccine conducted by Israeli scientists found that vaccination most likely caused myocarditis in one to five individuals per 100,000 who would not have developed the condition. Their study also found that young males were at highest risk for developing the condition. 

According to the CDC, as of October 6, 2021, 1,640 reports of myocarditis and pericarditis following COVID-19 mRNA vaccines had been reported to VAERS among persons 30 years of age and younger. Most cases have occurred in teenage boys. 

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Potential Risk of Microvascular Injury

In December 2020, Dr. J. Patrick Whelan, M.D., Ph.D, a practicing pediatric rheumatologist treating children with Multisystem Inflammatory Syndrome (MIS-C), submitted public comment to the U.S. Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) prior to the December 10, 2020 review meeting of the Pfizer-BioNTech COVID-19 vaccine. In his comments, Whelan expressed concern that vaccines focused on creating immunity to the SARS-CoV-2 spike protein might actually result in injuries. In particular, he warned that the mRNA vaccines produced by Pfizer-BioNTech and Moderna had “the potential to cause microvascular injury (inflammation and small blood clots called microthrombi) to the brain, heart, liver and kidneys in ways that were not assessed in the safety trials.” 

Health care providers treating persons with COVID-19 illness have documented significant damage to other organs besides the lungs and include conditions such as neurological dysfunction, blood clots, heart inflammation, acute kidney disease, liver and intestinal damage. Despite disease impact on other organs of the body, in most cases, the virus is absent or limited. This appears to suggest that the spike proteins alone may be capable of causing significant damage throughout the body, without evidence of the virus.  

In his comment, Whelan stated that “While there are pieces to this puzzle that have yet to be worked out, it appears that the viral spike protein that is the target of the major SARS-CoV-2 vaccines is also one of the key agents causing the damage to distant organs that may include the brain, heart, lung, and kidney.” He urged that testing be done of the heart and even tissues of vaccinated individuals to assess the effects of the vaccine and warned that:  

“As important as it is to quickly arrest the spread of the virus by immunizing the population, it would be vastly worse if hundreds of millions of people were to suffer long-lasting or even permanent damage to their brain or heart microvasculature as a result of failing to appreciate in the short-term an unintended effect of full-length spike protein-based vaccines on these other organs.”

Risk of Thrombosis with Thrombocytopenia Syndrome (TTS)

On April 13, 2021, the FDA and CDC paused use of the Janssen/Johnson & Johnson COVID-19 vaccine after serious blood clots were reported in women between the ages of 18 and 49.  By April 23, 2021, 15 cases and 3 deaths had been associated with the rare blood clot disorder, now referred to by health officials as thrombosis with thrombocytopenia syndrome (TTS). All cases were reported in women, with 2 occurring in women over 50 years of age. 

This blood clot disorder has also been associated with the AstraZeneca COVID-19 vaccine, another adenovirus vector vaccine, which has been authorized for use by the European Medicines Agencies (EMA). On April 7, 2021, the European Medicines Agency (EMA) safety committee (PRAC) concluded that “unusual blood clots with low blood platelets should be listed as very rare side effects of Vaxzevria (formerly COVID-19 Vaccine AstraZeneca).” In their report, PRAC reminded health care professionals and vaccine recipients to be aware of the possibility of “blood clots combined with low levels of blood platelets occurring within 2 weeks of vaccination.” PRAC reports that the blood clots occurred in the abdomen (splanchnic vein thrombosis), brain (cerebral venous sinus thrombosis or CVST), and arteries, in conjunction with low levels of blood platelets and at times with bleeding. 

According to PRAC, “One plausible explanation for the combination of blood clots and low blood platelets is an immune response, leading to a condition similar to one seen sometimes in patients treated with heparin (heparin induced thrombocytopenia, HIT).” New studies and revised protocols to ongoing clinical trials have been requested by safety officials. 

In a preprint study pending peer review released on April 20, 2021, German researchers describe what they believe to be the two-step mechanism responsible for the serious clotting reaction following the AstraZeneca COVID-19 vaccine. According to the scientists, the first step involves the activation of blood platelets when they come into contact with the adenovirus outer shell and the proteins from the cells where the vaccine grows. When this occurs in large numbers, a signal wakes up B-cells that then produces an enormous number of antibodies against the platelet factor 4 protein, which is what assists to coordinate blood clotting. When this occurs, the body believes that it is responding to a huge number of pathogens in the body, and causes antibodies to bind to the platelets, pull in white blood cells, and cause a systemic disruption. The second step involves the calcium-binder and stabilizer, EDTA, that is an ingredient in the AstraZeneca vaccine. EDTA causes the blood vessel walls to open up and permit entry of the protein and platelet complexes to begin circulation in the blood stream which triggers the syndrome. 

While many cases of the serious blood clotting disorder have occurred in women, lead author Dr. Andreas Greinacher reported that this disorder was not specific to one gender. Greinacher noted that since most health-care workers are women and part of the initial group of people to receive the vaccine, the tendency for cases to be reported among females was significantly higher. 

An in-depth review of 24 cases of splanchnic vein thrombosis and 62 cases of cerebral venous sinus thrombosis reported to the EU drug safety database, EudraVigilance, as of March 22, 2021 was completed by the committee. Of these cases, 18 were reported as fatal. The committee, however, continues to recommend the vaccine, stating that “The reported combination of blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.” 

As of April 22, 2021, more than 220 cases of blood clots in conjunction with low platelets had been reported following AstraZeneca vaccination.  Vaccine use has resumed in many countries; however, some countries have restricted use of the product to persons over the age of 60 or 65 years of age. As of April 19, 2021, the vaccine remained suspended in Cameroon, Norway, and Denmark.  On April 14, 2021, Danish health officials announced that it was halting use of the vaccine after studies had noted that blood clots occurred at a rate of one in 40,000 people. 

The CDC’s Advisory Committee on Immunization Practices (ACIP) voted to resume full use of the Janssen/Johnson & Johnson vaccine in all persons 18 years of age and older on April 23, 2021, by a vote of 10 to 4 (with one voting member abstaining due to a conflict of interest). Those who voted against the recommendation expressed concern regarding the lack of warning on the risk of TTS in women under 50 years of age.   

The FDA updated the Janssen/Johnson & Johnson’s COVID-19 Fact Sheet on April 23, 2021 and acknowledged that: 

“Reports of adverse events following use of the Janssen COVID-19 Vaccine under emergency use authorization suggest an increased risk of thrombosis involving the cerebral venous sinuses and other sites (including but not limited to the large blood vessels of the abdomen and the veins of the lower extremities) combined with thrombocytopenia and with onset of symptoms approximately one to two weeks after vaccination. Most cases of thrombosis with thrombocytopenia reported following the Janssen COVID-19 Vaccine have occurred in females ages 18 through 49 years; some have been fatal. The clinical course of these events shares features with autoimmune heparin-induced thrombocytopenia. In individuals with suspected thrombosis with thrombocytopenia following the Janssen COVID-19 Vaccine, the use of heparin may be harmful and alternative treatments may be needed. Consultation with hematology specialists is strongly recommended.”

By May 7, 2021, there had been 28 cases of TTS and 3 deaths confirmed by the CDC to be related to the Johnson & Johnson/Janssen COVID-19 vaccine. Moreover, TTS has been reported in men and in women between 50 and 60, in addition to women between 18 and 49 years. 

As of October 6, 2021, 47 cases of TTS following the Janssen/Johnson & Johnson COVID-19 vaccine had been confirmed by the CDC and FDA. 

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COVID-19 Vaccines and Menstrual Changes

Menstrual cycle changes have been reported following mRNA COVID-19 vaccines. These reports have included heavy menstrual periods, menstruation following menopause, breakthrough periods in women using birth control pills, and more. As a result of the numerous reports of menstrual cycle changes, Dr. Kate Clancy, associate professor of anthropology at the University of Illinois, launched an online survey on April 7, 2021, aimed at gathering more information from women on the effects of COVID-19 vaccination on menstruation. 

On August 30, 2021, the National Institutes of Health (NIH) announced that it had award grants totaling $1.67 Million dollars to five institutions to study whether a potential link exists between COVID-19 vaccines and menstrual changes in women. In their press release, NIH noted reports of menstrual changes, including missed and irregular periods, heavier menstrual flows, and other changes had been reported by women who had received COVID-19 vaccines. The research will also look at the underlying mechanisms involved in the menstrual changes as well as the length of time the changes last. 

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Risk of complications from mRNA COVID-19 Vaccines

The CDC cautions on the use of mRNA COVID-19 vaccines in persons who have a history of immediate allergic reaction to any injectable therapy or other vaccine, and states that precautions should be considered in consultation with an allergist-immunologist as follows: 

  • Persons with a contraindication to mRNA COVID-19 vaccines (including known PEG allergy) may be given to vaccination with Janssen COVID-19 vaccine.
  • Persons who have received the first dose of an mRNA COVID-19 and who have a contraindication to the second dose, should wait at least 28 days before receiving the Janssen COVID-19 vaccine.

In clinical trials, persons who have previously received dermal fillers experienced swelling at or near the site of filler injection. Persons with a history of receipt of dermal filler may be a higher risk of complications following mRNA COVID-19 vaccination. 

Persons who have pre-existing immunity to SARS-CoV-2 may also be at increased risk of severe reactogenicity following mRNA COVID-19 vaccination. In a study conducted by researchers from the Icahn School of Medicine at Mount Sinai, persons with pre-existing immunity to SARS-CoV-2 who received mRNA COVID-19 vaccines were found to have significantly higher rates of systemic reactions when compared to those who were not immune at the time of vaccination. Systemic reactions included fatigue, headache, chills, fever, joint or muscle pains.   

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Risk of complications from Janssen/Johnson & Johnson Non-Replicating Viral Vector Vaccine

Persons with a history of severe allergic reaction or immediate allergic reaction to any ingredient contained within the Janssen/Johnson & Johnson COVID-19 vaccine may be at increased risk for complications following vaccination. 

On April 23, 2021, the FDA updated the Janssen/Johnson & Johnson COVID-19 Vaccine Fact Sheet with a warning regarding the risk of thrombosis with thrombocytopenia syndrome (TTS), a serious and potentially fatal syndrome involving blood clots in combination with thrombocytopenia (low blood platelets). According to the Fact Sheet:  

“an increased risk of thrombosis involving the cerebral venous sinuses and other sites (including but not limited to the large blood vessels of the abdomen and the veins of the lower extremities) combined with thrombocytopenia and with onset of symptoms approximately one to two weeks after vaccination. Most cases of thrombosis with thrombocytopenia reported following the Janssen COVID-19 Vaccine have occurred in females ages 18 through 49 years; some have been fatal.”

Symptoms of TTS include seizures, fainting, backache, blurred vision, severe headache, severe abdomen or stomach pain, severe chest pain, shortness of breath, petechiae (tiny red spots on the skin), leg swelling, or new or easy bleeding or bruising. 

On July 13, 2021, the FDA announced revisions to the Fact Sheet for Healthcare Providers Administering the Johnson & Johnson/Janssen COVID-19 vaccine and the Fact Sheet for Recipients and Caregivers to include information regarding an increased risk of Guillain-Barré Syndrome (GBS) following vaccination. GBS, a serious neurological disorder where the body’s immune system attacks the peripheral nervous system, can cause muscle weakness, paralysis, and even death. According to the press release, the FDA reported 100 cases of GBS following vaccination, with 95 considered serious and requiring hospitalization, and one death. Government health officials noted that there was insufficient evidence to establish a causal relationship between the Johnson & Johnson/Janssen COVID-19 vaccine and GBS, and reported that “the known and potential benefits clearly outweigh the known and potential risks.” 

As of October 6, 2021, 228 cases of GBS following the Janssen/Johnson & Johnson COVID-19 had been identified in the VAERS data. According to the CDC, most cases occurred within 2 weeks of vaccination and among men, primarily those aged 50 and older. 

In early September 2021, the European Medicines Agency reported that its Pharmacovigilance Risk Assessment Committee (PRAC) was investigating a link between the Johnson & Johnson/Janssen COVID-19 vaccine and venous thromboembolism (blood clots in the veins). According to PRAC, in the initial clinical trials of the vaccine, a higher rate of venous thromboembolism was noted in the vaccine group when compared to the placebo group. Additional data collected from two larger clinical trials were expected to be submitted to PRAC in advance of vaccine marketing authorization, to determine whether the condition was linked to vaccination.   

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Interchangeability of COVID-19 Vaccines

Currently the CDC has stated no preference for vaccine usage and acknowledges that evaluation of efficacy using a mixed-product series and recommends that the same product be used to complete the series.<a href=" name="_ednref93">93 However, the CDC also states that persons that have a contraindication to one of the mRNA COVID-19 vaccines should not receive a second dose, and may be able to receive the Janssen/Johnson & Johnson COVID-19 vaccine, and vice versa, provided precautions are followed. 

The University of Oxford is currently studying the use of different combinations of COVID-19 vaccines in persons 50 years of age and older. As of October 1, 2021, studies were ongoing to evaluate the safety and effectiveness of using a different COVID-19 vaccine as the second vaccine dose. Vaccines involved in the clinical trials included Pfizer-BioNTech, Moderna, AstraZeneca, and Novavax.  Preliminary results are expected by early summer 2021 but the study is expected to continue for at least one year. 

According to a study published in The Lancet on May 12, 2021, adults 50 years and older who received a mixed dose combination of the Pfizer-BioNTech vaccine and the AstraZeneca COVID-19 vaccines experienced more mild and moderate side effects than those administered only one type of vaccine. Systemic reactions, especially fever, were significantly higher after the second vaccine dose in persons who received the AstraZeneca vaccine followed by a dose of the Pfizer-BioNTech vaccine when compared to persons who received two doses of the Pfizer-BioNTech vaccine. There were also more reports of joint and muscle pain, chills, malaise, fatigue, and headache after the second vaccine dose in person who received a mixed dose schedule. 

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IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

Updated October 20, 2021

 

Who should not get the COVID-19 vaccine?

who should not get

Contraindications

Below are the age groups authorized to receive COVID-19 vaccines, as approved or authorized by the U.S. Food and Drug Administration (FDA): 

Pfizer-BioNTech/COMIRNATY 

  • COMIRNATY mRNA vaccine (30 mcg) is FDA approved for use in persons 12 years and older. The FDA has also determined that COMIRNATY is interchangeable with the 30mcg Pfizer-BioNTech mRNA vaccine, which also has an EUA status. This means that both vaccines can be used interchangeably in individuals 12 years and older. Persons under 12 years of age should not receive this vaccine.1
  • Pfizer-BioNTech mRNA vaccine (10mcg) dose is authorized for use in children five through 11 years under EUA status. Children under five years should not receive this vaccine.2
  • Pfizer-BioNTech mRNA vaccine (3mcg) dose is authorized for use in children six months through five years under EUA status. Children under six months or over four years should not receive this vaccine.3

 Moderna/Spikevax

  • Spikevax mRNA vaccine (100mcg) is FDA approved for persons 18 years of age and older. Persons under 18 years of age should not receive this vaccine.4
  • Moderna mRNA vaccine (100mcg) is authorized for persons 12 years of age and older. Persons under 12 years of age should not receive this vaccine.5
  • Moderna mRNA vaccine (50mcg) is authorized under EUA for children six through 11 years of age. Children under six years or over 11 years should not receive this vaccine.6
  • Moderna mRNA vaccine (25mcg) is authorized under EUA for children six months through five years of age. Children under six months or over five years should not receive this vaccine.7

 Janssen/Johnson & Johnson

  • Janssen/Johnson & Johnson viral vector vaccine is authorized under EUA for persons 18 years of age and older. Persons under 18 years of age should not receive this vaccine.8

 Novavax

  • Novavax COVID-19 vaccine is authorized under EUA for persons 12 years of age and older. Persons under 12 years of age should not receive this vaccine.9

Vaccine Coadministration

No data is available on the safety of administering mRNA COVID-19 vaccines with other vaccines. When COVID-19 vaccines were initially authorized for use, CDC health officials recommended that COVID-19 vaccines be administered alone, and not within 14 days of receiving another vaccine.10

However, at the May 12, 2021 CDC ACIP meeting, health officials updated their guidance and stated that the COVID-19 vaccine could be co-administered with other vaccines, despite a lack of data to support this recommendation.11 12 The CDC stated that their initial guidance recommending that COVID-19 vaccines be administered alone was not based on safety immunogenicity concerns, but rather out of an abundance of caution. The CDC acknowledges that data on health outcomes and reactogenicity of coadministration of COVID-19 vaccines with other routinely administered vaccines is lacking.13

The CDC advises that young adult males who receive an orthopoxvirus (smallpox,  monkeypox) vaccine such as ACAM2000 or JYNNEOS vaccine should consider delaying COVID-19 vaccination for at least four weeks due to the risk of myocarditis and pericarditis. Myocarditis and pericarditis have been associated with mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech), Novavax COVID-19 vaccine, and ACAM2000 smallpox vaccine. There is also an unknown risk of myocarditis and pericarditis with JYNNEOS vaccine. However, if orthopoxvirus vaccination is recommended due to a potential monkeypox virus exposure, the CDC does not recommend the four-week delay between COVID-19 vaccination.14

Vaccine Contraindications

According to CDC interim clinical consideration guidelines for use of COVID-19 vaccines published on August 22, 2022, contraindications to receiving the Moderna, Pfizer-BioNTech, and/or Janssen/Johnson & Johnson vaccine include a history of:15

  • Severe allergic reaction to any ingredient contained within the vaccine or after a previous dose of the COVID-19 vaccine;
  • Immediate allergic reaction of any seriousness to any ingredient contained within the vaccine (including polyethylene glycol [PEG) or diagnosed allergy to a COVID-19 vaccine ingredient;

The CDC also states that persons that have a contraindication to one of the mRNA COVID-19 vaccines should not receive a second dose, and may be able to receive the Janssen/Johnson & Johnson COVID-19 vaccine, and vice versa, provided precautions are followed.  

Persons with an allergy to polysorbate may receive mRNA COVID vaccines, though previously this was considered a contraindication due to potential cross-reactive hypersensitivity to the polyethylene glycol (PEG) contained in these vaccines. However, a polysorbate allergy remains as a contraindication to receiving the Janssen/Johnson & Johnson COVID-19 vaccine. Guidance encourages providers to make distinctions between true allergic reactions versus other types of reactions, such as syncope or other vaccine side effects, to more accurately determine if a person who has reacted should receive a second dose of an mRNA COVID-19 vaccine.16

Precautions

Individuals with a history of previously receiving dermal fillers have experienced swelling near or at the site of filler injection after mRNA COVID-19 vaccine. While a history of receipt of dermal fillers is not a contraindication to receiving mRNA COVID-19 vaccines, the CDC advises that anyone who experiences swelling after vaccination should contact their health care provider immediately.17

The CDC cautions on the use of mRNA COVID-19 vaccines in persons who have a history of immediate allergic reaction to any injectable therapy or other vaccine, and states that precautions should be considered in consultation with an allergist-immunologist as follows:18

  • Persons with a contraindication to mRNA COVID-19 vaccines (including known PEG allergy) may be given to vaccination with Janssen/Johnson & Johnson COVID-19 vaccine.
  • Persons who have received the first dose of an mRNA COVID-19 and who have a contraindication to the second dose, should wait at least 28 days before receiving the Janssen/Johnson & Johnson COVID-19 vaccine.
  • Persons with a contraindication to Janssen/Johnson & Johnson COVID-19 vaccine (including diagnosed polysorbate allergy) may be given mRNA COVID-19 vaccines, and notes that polysorbate allergy is a precaution.

Special Populations and Conditions

Myocarditis and Pericarditis

According to the CDC, there is insufficient data on the safety or efficacy of COVID-19 vaccine in persons with a past history of myocarditis and pericarditis. The CDC, however, has stated that persons with a history of myocarditis and pericarditis that is unrelated to vaccination be vaccinated once symptoms have fully resolved. In persons who develop myocarditis or pericarditis following receipt of an mRNA or Novavax COVID-19 vaccine, the CDC recommends that the second dose be deferred.19

The CDC also states that a second dose of mRNA vaccine can be considered in certain circumstances in this population following complete resolution of symptoms. These circumstances may include risk of severe illness, community spread, person infection risk, as well as the availability of additional data on the safety and long-term health outcomes of this population.20

Immunocompromised Populations

According to the Pfizer-BioNTech, Moderna, Novavax, and Johnson & Johnson/Janssen Fact Sheet for Healthcare Providers Administering Vaccine, as well as the COMIRNATY mRNA COVID-19 vaccine and SPIKEVAX mRNA COVID-19 vaccine, individuals who are immunocompromised, including persons receiving immunosuppressive therapies, may not have an adequate immune response to vaccination. 21 22 23 24 25 26 Persons with certain immunosuppressive conditions who have previously received two doses of mRNA COVID-19 vaccines may receive a third dose of mRNA COVID-19 vaccine although it is not known whether a subsequent dose will offer any additional benefit. The third dose is recommended to be administered at least 28 days following the second dose.27 A fourth vaccine dose has also been authorized in certain immunocompromised populations, to be administered at least six months following administration of a third dose.28

A study published by the CDC in November of 2021 reported that 53 percent of immunocompromised individuals who were hospitalized with symptoms of COVID-19 vaccine were fully vaccinated. It is possible that the number of fully vaccinated may have been higher as the study excluded individuals who received a dose of the Janssen/Johnson & Johnson vaccine and those who had received their second mRNA vaccine dose less than two weeks before hospitalization.29

Previous History of Monoclonal Antibody or Convalescent Plasma Use

There is a lack of safety data on the use of mRNA COVID-19 vaccines in persons who have been treated for COVID-19 illness using monoclonal antibodies or convalescent plasma. Prior to February 11, 2022, as evidence appears to indicate that reinfection with SARS-CoV-2 virus is uncommon within 90 days of initial infection, health officials recommend that COVID-19 vaccination be deferred for at least three months following receipt of antibody therapy due to active infection.30 On February 11, 2022, the CDC updated its recommendation and stated that persons treated with monoclonal antibodies could receive a COVID-19 vaccine at any time. Persons who received tixagevimab/cilgavimab (EVUSHELD™), however, were recommended to wait at least 14 days before receiving a dose of COVID-19 vaccine.31

Pregnancy and Lactation

According to the Pfizer-BioNTech, Moderna, Novavax, and Johnson & Johnson/Janssen Fact Sheet for Healthcare Providers Administering Vaccine, as well as the COMIRNATY mRNA COVID-19 and SPIKEVAX mRNA COVID-19 vaccine package insert, there is insufficient data to determine the safety of COVID-19 vaccines in pregnant women, and it is not known whether these vaccines can cause harm to the mother or developing baby. There is also no safety data on the use of mRNA COVID-19 vaccines in lactating women, or the effects of the vaccine on the breastfed baby. 32 33 34 35 36 37

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

What questions should I ask my doctor about COVID-19 vaccines?

questions

NVIC If You Vaccinate, Ask 8! Webpage downloadable brochure suggests asking eight questions before you make a vaccination decision for yourself, or for your loved one. If you review these questions before your appointment, you will be better prepared to ask your healthcare provider questions. 

Vaccine providers are federally required to provide vaccine recipients with the vaccine risk information, which can be found on the relevant FDA COVID-19 Vaccine Fact Sheet. Vaccine providers must also inform COVID-19 vaccine recipients that the vaccine may be decline and must providing information on consequences of declining the vaccine.

To be more fully informed about COVID-19 vaccines, FDA Fact Sheets are available to the public on the FDA's website, and NVIC encourages the public to read these fact-sheets prior to vaccination to assist consumers in making an informed vaccination decisions and for use in asking questions of vaccine providers. Because the FDA has granted all COVID-19 vaccines in use in the U.S. with an EUA status, all vaccine injury claims are governed by the Countermeasures Injury Compensation Program (CICP) and the U.S. Centers for Disease Control and Prevention (CDC) is not legally required to create a Vaccine Information Statement (VIS).  In this instance, the FDA issues Fact Sheets on EUA status vaccines which perform a similar function to the CDC’s VIS.

NVIC provides the public with referenced information on diseases and vaccines to empower informed decision-making and encourages consumers to further explore these references as vaccine decisions are made.

Additional questions to ask

Other questions that may be useful to discuss with your doctor before getting the COVID-19 vaccine are: 

  • What should I do if my child or I become ill after vaccination?
  • What other kinds of reaction symptoms should I call to report after COVID-19 vaccination?
  • If the coronavirus vaccine doesn’t protect me or my child, do we have any other options for preventing coronavirus infection?

In alignment with the informed consent ethic, which has guided the ethical practice of modern medicine, vaccine providers should answer your questions, and/or provide you with resources to learn more. The informed consent ethic, which is recognized globally as a human right, also states that individuals should be able to delay or refuse treatments and interventions without coercion or punishment. 

Under federal law, vaccine providers are required to report vaccine adverse events to the federal Vaccine Adverse Event Reporting System (VAERS) that is co-administered by the CDC and FDA.  You can learn more about reporting vaccine reactions on NVIC’s reaction reporting webpage and can also directly report vaccine reactions to VAERS.

Remember, if you choose to vaccinate, always keep a written record of exactly which shots/vaccines you or your child have received, including the manufacturer’s name and vaccine lot number. Write down and describe in detail any serious health problems that develop after vaccination and keep vaccination records in a file you can access easily.  

It also is important to be able to recognize a vaccine reaction and seek immediate medical attention if the reaction appears serious, as well as know how to make a vaccine reaction report to federal health officials at the Vaccine Adverse Reporting System (VAERS). NVIC’s Report Vaccine Reactions—It’s the Law webpage can help you file a vaccine reaction report yourself to VAERS if your doctor fails or refuses to make a report.

Vaccine Injury Compensation for COVID-19 EUA Vaccines

In the U.S., vaccine manufacturers are shielded from liability under the 2005 Public Readiness and Emergency Preparedness (PREP) Act for vaccines developed in response to a health emergency.   

The Secretary of Health and Human Services (HHS) invoked the PREP Act following the January 31, 2020 declaration of a COVID-19 pandemic public health emergency, stating that vaccines and drugs developed to respond to the coronavirus pandemic were covered countermeasures under the 2005 PREP Act. 

Individuals who die or suffer serious harm due to the administration of covered countermeasures, such as vaccines, may be eligible to receive compensation through the Countermeasures Injury Compensation Program (CICP),  whether the harm was a result of willful misconduct on the part of the vaccine manufacturer or person administering the vaccine.

The CICP is administered by employees in HHS’s Health Resources and Services Administration (HRSA). HHS regulations govern CICP’s procedures and eligibility determinations. In general, eligible individuals (or their survivors) who suffer death or serious physical injury directly caused by the administration of a covered countermeasure may receive reimbursement for reasonable medical expenses, loss of employment income and survivor benefits in the case of death. Serious physical injuries under CICP are generally limited to those that warrant hospitalization or result in a significant loss of function or disability. Congress funds CICP awards through emergency appropriations to the Covered Countermeasure Process Fund. 

The CICP currently governs all vaccine injury claims for COVID-19 vaccines in use in the U.S. and this program has been previously used when a public health emergency was declared for the H1N1 “swine flu” influenza pandemic in 2009 and for the Ebola virus outbreak in 2016. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice. 

 

Updated October 20, 2021

 

NVIC Selected Resources, Statements and Commentaries Related to SARS-CoV-2 and COVID-19

NVIC Answers to Frequently Asked Questions

NVIC COVID-19 Articles & Reports

NVIC’s The Vaccine Reaction COVID-19 Articles

 

 

 

 

SARS-CoV-2 Virus & COVID-19 Quick Facts

covid-19

SARS-CoV-2 & COVID-19

  • SARS-CoV-2 is one strain (type) of coronavirus that is part of a large family of enveloped RNA viruses that can infect mammals and birds.1 Coronaviruses are named for their crown-like spiked surfaces and cause generally mild respiratory symptoms like the common cold in humans.2
  • A few coronavirus strains can cause very severe respiratory disease with significant mortality, such as Severe Acute Respiratory Syndrome (SARS) that emerged in China in 2002-20033 and Middle Eastern Respiratory Syndrome (MERS) that was first reported in Saudi Arabia in 2012.4 SARS-CoV-2, which was identified in China in late 20195 and declared a global pandemic by the World Health Organization (WHO) in March 2020,6 7 has a much lower mortality rate than SARS or MERS.8
  • People with SARS-CoV-2 infections can be asymptomatic9 or exhibit a constellation of mild or severe illness symptoms known as COVID-19, which include fever; chills; cough; shortness of breath/difficulty breathing, fatigue; muscle, joint or body aches; rash; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting, and diarrhea.10 Multiple studies have found that individuals who recover from COVID-19 illness have long-term immunity and rarely suffer a second COVID-19 infection. 11 12 13 14
  • Complications of COVID-19 disease include pneumonia; acute respiratory distress syndrome (ARDS); acute kidney, liver, and heart failure or damage; septic shock; disseminated intravascular coagulation (DIC); rhabdomyolysis (muscle breakdown); chronic fatigue syndrome; blood clots and death.15 Serious complications of COVID-19 disease may be caused by a hyperactive immune response known as a cytokine storm, which occur when an infection triggers the immune system to flood the bloodstream with inflammatory proteins (cytokines) that can damage organs and kill tissue.16 In some young children and adolescents, SARS-CoV-2 infections may trigger multisystem inflammatory syndrome (MIS-C).17 18
  • According to the U.S. Centers for Disease Control and Prevention (CDC), in 2020 about 94 percent of COVID-19 related-deaths occurred in persons over age 65 and individuals with underlying poor health conditions. This means that only about 6 percent of COVID-19 related-deaths involved persons who did not have any pre-existing health conditions or in persons under the age of 65.19 Among those the CDC consider to be at highest risk for severe COVID-19 disease are the immunocompromised; pregnant women; individuals with chronic heart, lung or kidney disease; the obese; type 2 diabetics; and individuals with cancer, Down’s syndrome, sickle cell disease and thalassemia. There are other chronic health conditions that might increase risks for severe COVID-19 disease, including asthma, high blood pressure, dementia and neurologic conditions, liver disease, cystic fibrosis, and type 1 diabetes.20

COVID-19 Vaccine

  • On Mar. 10, 2020, the Secretary of Health and Human Services (HHS) invoked the 2005 Public Readiness and Emergency Preparedness (PREP) Act, after declaring that the COVID-19 pandemic was a public health emergency. As a result, manufacturers of COVID-19 vaccines that have been developed to respond to the SARS-CoV-2 pandemic are considered public health emergency “countermeasures”. The PREP Act shields manufacturers and vaccine providers from liability and vaccine injury compensation claims will be processed by the Countermeasures Injury Compensation Program (CICP).21 22 23
  • The FDA has licensed two COVID-19 vaccines for use in the U.S.: Comirnaty mRNA COVID-19 vaccine24, developed and manufactured by Pfizer-BioNTech, and Spikevax mRNA COVID-19 vaccine25, developed and manufactured by Moderna with NIAID. Comirnaty is approved as a two-dose series in individuals 12 years and older, while Spikevax is approved as a two-dose series in persons 18 and older.
  • As of August 28, 2022, the Pfizer-BioNTech mRNA COVID-19 vaccine remains authorized for use under Emergency Use Authorization (EUA) in children six months through 12 years.26 The Moderna mRNA COVID-19 vaccine also remains under EUA, and available for use in infants, children, and adolescents six months through 17 years.27 An EUA granted by the FDA to pharmaceutical corporations for distribution of experimental COVID-19 vaccines in the U.S. does not mean that the agency has evaluated all safety and efficacy data and officially approved licensure of the vaccine. The EUA authorizes manufacturers to release an experimental vaccine for voluntary use and the FDA states that vaccine recipients must “have the option to accept or refuse the vaccine.”28
  • In February 2021, Janssen Biotech, Inc. of Johnson & Johnson, was granted an EUA by the FDA for an experimental COVID-19 vaccine, which uses a human adenovirus vector29 30 31 rather than mRNA technology, for persons 18 and older.32 On April 13, 2021, the FDA and CDC paused use of the vaccine after serious blood clots with low blood platelets were reported in women between the ages of 18 and 49, a condition now referred to as Thrombosis with Thrombocytopenia (TTS).33 Ten days later, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to resume use of the vaccine despite the known risks. 34 35 On December 16, 2021, ACIP voted to give a preferential recommendation to mRNA COVID-19 vaccines over the Johnson & Johnson/Janssen COVID-19 vaccine due to the risk of TTS.36 The Johnson & Johnson/Janssen COVID-19 vaccine remains available for use in the U.S. but is recommended only when a person is unable to or unwilling to receive an mRNA COVID-19 vaccine, or when mRNA COVID-19 vaccines are not available.37
  • On July 13, 2022, the FDA authorized use of the Novavax COVID-19 vaccine, adjuvanted for individuals 18 years of age and older. This vaccine, administered as a 2-dose primary series given three weeks apart, is a protein subunit vaccine that uses recombinant nanoparticle technology. The adjuvant in the vaccine is the Matrix M-adjuvant and contains saponin extracts from the bark of the Soapbark tree. The spike protein in the vaccine is produced in insect cells It is approved for use in individuals who have not previously received a dose of COVID-19 vaccine.38 In August 2022, the FDA expanded use of the vaccine in persons 12 years of age and older.39 As of August 28, 2022, booster doses of Novavax in persons who received a two-dose primary series of Novavax have not yet been authorized by the FDA.40
  • As of August 28, 2022, booster doses of mRNA COVID-19 vaccines have been authorized under EUA by the FDA and recommended for all persons five years of age and older.41 Persons 50 years of age and older may also choose to receive a second booster dose, to be given at least four months following receipt of the first booster dose.42 Individuals who are immunocompromised are recommended to receive a 3-dose primary series of mRNA vaccine, followed by a booster dose at least three months after the third vaccine dose. A second booster dose may also be given at least four months after the first booster dose.43 The FDA and CDC have authorized the mixing of vaccine types for all persons 18 years and older who are receiving booster doses44 despite limited safety or efficacy data to support the use of a mixed dose schedule.45
  • As of July 24, 2022, health officials at the World Health Organization (WHO) and U.S National Institutes of Health (NIH) have warned that, while there is evidence that two doses of the Pfizer-BioNTech and Moderna vaccines can prevent symptomatic COVID-19 disease, there is a lack of evidence that the vaccines are effective in preventing infection and transmission of SARS-CoV-2.46 47 48 49 The Janssen/Johnson & Johnson vaccine was also granted an EUA based on efficacy data that demonstrated evidence for protection against symptomatic COVID-19 disease rather than protection against infection and transmission of the new coronavirus.50
  • As of the July 15, 2022 release of data from CDC, there have been 1,350,950 reports of adverse events following vaccination with COVID-19 vaccines submitted to the federal vaccine adverse event reporting system (VAERS), which noted 246,676 serious adverse events; 33,009 life-threatening events; 169,426 hospitalizations; and 29,635 deaths. Reported adverse events have also included pain at the injection site; fatigue; anaphylaxis; headache; muscle and joint pain; fever; chills;51 swollen lymph nodes; nausea and vomiting;52 immune thrombocytopenia purpura (ITP) (low blood platelets);53 54 Bell’s Palsy;55 tinnitus;56 cardiac arrest; neurological dysfunction; rheumatoid arthritis; blood clots; heart, kidney and liver failure;57 anaphylaxis; myocarditis and pericarditis; 58 Guillain-Barré syndrome (GBS)59 and death.60 61 62 Click for most recent CDC data release.
  • The CDC states that contraindications to receiving COVID-19 vaccines include (1) a history of severe allergic reaction to a previous vaccine dose or any of its ingredients; (2) a history of an immediate allergic reaction of any severity to a previous mRNA COVID-19 vaccine dose or to any of its ingredients. A polyethylene glycol (PEG) allergy is considered a contraindication to mRNA vaccines, while a polysorbate allergy is considered a contraindication to Janssen vaccine. The CDC states that a person with a contraindication to mRNA vaccination may be able to receive the Janssen vaccine and vice versa provided that precautions are taken. This includes ensuring that the vaccine is administered by a healthcare provider who is equipped to manage severe allergic reactions.63 A prior history of TTS after receipt of the Janssen COVID-19 vaccine or another adenoviral-vector COVID-19 vaccine is also a contraindication to receiving a dose of the Johnson & Johnson/Janssen vaccine.64


Food & Drug Administration (FDA)

Centers for Disease Control (CDC)            

CDC – Coronavirus Disease (COVID-19)

National Institutes of Health – NIH

Coronavirus Disease (COVID-19)

Vaccine Reaction Symptoms & Ingredients

Our Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and more.

Search for Vaccine Reactions

NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts examines symptoms, reactions, vaccines, dates, places, and more. 

Reporting a Vaccine Reaction

Since 1982, the NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is the law. If your doctor will not report a reaction, you have the right to report a suspected vaccine reaction to VAERS. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

 

References:

1 U.S. Centers for Disease Control and Prevention. How COVID-19 Spreads. In: COVID-19. Aug. 11, 2022.

2 Rivett L, Sridhar S, Sparkes D, et al. Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission. ELife 2020; 9:e58728.

3 U.S. Centers for Disease Control and Prevention. Symptoms of COVID-19. In: COVID-19. Aug. 11, 2022.

4 WebMD. Complications Coronavirus Can Cause Aug. 9, 2021.

5 Alejo JL, Mitchell J, Chang A, et al. Prevalence and Durability of SARS-CoV-2 Antibodies Among Unvaccinated US Adults by History of COVID-19. JAMA Mar 15, 2022;327(11):1085-1087.

6 Washington University School of Medicine in St. Louis. Good news: Mild COVID-19 induces lasting antibody protection. May 24, 2021.

7 Gazit S, Shlezinger R, Perez G, et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. medRxiv Aug. 25, 2021.

8 Tregoning JS, Brown ES, et al. Vaccines for COVID-19. Clin Exp Immunol. 2020 Nov;202(2):162-192.

9 Cohen J. Vaccine designers take first shots at COVID-19Science Magazine Apr. 3, 2020.

10 Malarkey MA, Gruber MF. BLA Approval – BioNTech Manufacturing GmbH. U.S. Food and Drug Administration Aug. 23, 2021.

11 Olsen M. BLA Approval - ModernaTX, Inc. U.S. Food and Drug Administration Jan. 31, 2022.

12 U.S. Food and Drug Administration. Spikevax and Moderna COVID-19 Vaccine. July 1, 2022.

13 U.S. Food and Drug Administration. FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine. Feb. 27, 2021.

14 World Health Organization. COVID-19 vaccine tracker and landscape. Aug. 26, 2022.

15 Knapp A, Rosenbaum L. Here’s What You Need to Know About Astra Zeneca’s COVID-19 Vaccine. Forbes Nov. 23 2020.

16 Robert-Guroff M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol. December 2007;18(6):546-556.

17 U.S. Centers for Disease Control and Prevention. Vaccination to Prevent COVID-19 Outbreaks with Current and Emergent Variants — United States, 2021. In: Emergency Preparedness and Response. July 27, 2021.

18 Anderson M. Pfizer shot 39% effective against infection in Israel; 91% effective against severe disease. Becker’s Hospital Review July. 23, 2021.

19  The PREP Act and COVID-19: Limiting Liability for Medical Countermeasures. Congressional Research Service. Apr. 13, 2022.

20 21 U.S. Code § 360bbb–3(a)(2)(B) – Authorization for medical products for use in emergencies – Approval Status of Product. Cornell Law School.

21 U.S. Centers for Disease Control and Prevention. Frequently Asked Questions about SARS. In: Severe Acute Respiratory Syndrome (SARS). May 3, 2005.

22 U.S. Centers for Disease Control and Prevention. About MERS. In: Middle East Respiratory Syndrome (MERS). Aug. 2, 2019.

23 Wu YC, Chen CS, Chan YS. The outbreak of COVID-19: An overview. J Chin Med Assoc March 2020; 83(3): 217-220.

24 Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed March 2020; 91(1): 157-160.

25 Fisher BL. Coronavirus (COVID-19) Pandemic: NVIC Special Report. National Vaccine Information Center (NVIC) February-June 2020. 

26 Hewings-Maven Y. How do SARS and MERS compare with COVID-19? Medical News Today Apr. 10, 2020.

27 Garg S, Kim L, Whitaker M, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020. MMWR 2020; 69(15): 458-464.

28 U.S. Centers for Disease Control and Prevention. People with Certain Medical Conditions. In: COVID-19. May 2, 2022.

29 Congressional Research Service. The PREP Act and COVID-19: Limiting Liability for Medical Countermeasures. Apr. 13, 2022.

30 Garde D., Branswell H. 6 burning questions Congress could push Covid-19 vaccine makers to answer todayStat News July 20, 2020.

31 Fisher BL. Parpia R. 2005 PREP Act and 1986 Act Shield Vaccine Manufacturers from Liability The Vaccine Reaction Aug. 10, 2020.

32 U.S. Food and Drug Administration. Comirnaty and Pfizer-BioNTech COVID-19 Vaccine. July 11, 2022.

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