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Who is at highest risk for complications from the COVID-19 vaccine?
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.
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.
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.
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.
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.
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.
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.
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.
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.Back to Topic Links
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.
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
3 U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee December 10, 2020 Meeting Briefing Document- FDA. Dec. 10, 2020.
4 U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee December 17, 2020 Meeting Briefing Document - FDA. Dec. 17, 2020.
5 U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee February 26, 2021 Meeting Briefing Document- FDA. Feb. 26, 2021.
6 Cohen J. Could certain COVID-19 vaccines leave people more vulnerable to the AIDS virus? American Association for the Advancement of Science Oct. 19, 2020.
7 Hart R. Researchers Warn Some Covid-19 Vaccines Could Increase Risk Of HIV Infection. Forbes Oct. 20, 2020.
8 Cohen J. Could certain COVID-19 vaccines leave people more vulnerable to the AIDS virus? American Association for the Advancement of Science Oct. 19, 2020.
9 News Wires Hungary to start Covid-19 vaccinations with Russia’s Sputnik V, bypassing EU regulator. France 24 Feb. 12, 2021.
11 Cáceres M. How Will Unhealthy Americans React to COVID-19 Vaccines? The Vaccine Reaction Oct. 5, 2020.
12 Attkisson S. Deaths of Elderly Who Recovered From COVID-19, but Died After Vaccine, Raise Questions. The Epoch Times Feb. 10, 2021.
13 TVR Staff. Four Persons Die Days After COVID-19 Vaccinations in Portugal, Switzerland and Norway. The Vaccine Reaction Jan. 11, 2021.
14 Hendler C. 32 Nursing Home Residents Die in COVID-19 Outbreak During Mass Vaccination Drive. The Vaccine Reaction Jan. 24, 2021.
15 Torjesen I. Covid-19: Norway investigates 23 deaths in frail elderly patients after vaccination. BMJ January 2021; Pg. 372.
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