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How effective are COVID-19 vaccines?
To learn the history of the original monovalent COVID-19 vaccines developed for visit NVIC’s What is the history of COVID-19 vaccines in America webpage.
At this time effectiveness of the 2023-2024 COVID-19 vaccine containing the SARS-CoV-2 Omicron XBB.1.5 variant is unknown, as effectiveness is based on real-world data of how the vaccine works in the general population and this vaccine has just been recently approved and authorized for use in the general population.
The vaccine efficacy for the 2023-2024 monovalent COVID-19 vaccine containing the SARS-CoV-2 Omicron variant XBB.1.5 is also unknown as clinical trial were not done prior to their approval for use. 1 Approval and authorization of these vaccines were based on clinical trial data from the original COVID-19 vaccine, as well as bivalent COVID-19 vaccines that were never approved or authorized for use.2 3 4 5
Vaccine efficacy is based on ideal situations like well-designed clinical trials. Notably, vaccine efficacy can differ from vaccine effectiveness because a vaccine may not work as well in the real world. 6 7
Understanding what efficacy and effectiveness mean is also important. Below is an example from Yale Medicine.
“An example: Imagine there were 100 people in the vaccine group, and 100 people in the placebo group. If 10 people in the placebo group became infected, but only 2 in the vaccine group got sick, that means the vaccine has reduced the chances of illness by 80%; thus, it is considered to have an efficacy of 80%.”8
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.39
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.40 It is not yet known how long vaccine-acquired immunity from the Pfizer-BioNTech vaccine will persist.41
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.42
In a published editorial, associate editor of the British Medical Journal (BMJ), Dr. Peter Doshi, questioned Pfizer-BioNTech’s efficacy data:43
“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.)[44
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.45
There was also 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).46
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.47 In the spring of 2021, Pfizer-BioNTech began testing their product for use in children 12 to 15 years of age.48 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.49 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.50
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 old51 and the CDC’s ACIP voted to approve its use in this population on May 12, 2021.52
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.53 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.54
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.” 55
The FDA authorized use of a 10-mcg dose of Pfizer-BioNTech mRNA vaccine for use in children 5 through 11 years of age under EUA on October 29, 2021. This vaccine is recommended to be administered in a two-dose series, three weeks apart.56
The authorization of the Pfizer-BioNTech vaccine in children 5 through 11 years was based on two cohort studies involving 3,100 children who received the vaccine, and 1,538 children who received a placebo. Only 1,444 vaccine recipients, those involved in the cohort 1 study, were monitored for safety and effectiveness at least two months after the second vaccine dose. Data from children enrolled in the cohort 2 study was limited to only 2.4 weeks following the second vaccine dose.57
The FDA reported that the Pfizer-BioNTech 10-mcg vaccine was 90.7 percent effective at preventing infection. In clinical trials, three children who received the vaccine and 16 children who received the placebo developed COVID-19. No severe cases or deaths occurred among any children who developed COVID-19 infection. The FDA also reported that the immune responses to the 10-mcg vaccine in children 5 through 11 years were comparable to those from individuals 16 through 25 years who received the 30-mcg vaccine dose.58
A pre-print study pending peer review on the effectiveness of the Pfizer-BioNTech vaccine in children 5 – 11 years completed in New York State in December 2021 and January 2022 reported a decline in vaccine effectiveness from 65 percent to 12 percent by 28-34 days.59
In June 2022, the FDA authorized use of Pfizer-BioNTech COVID-19 mRNA vaccine under EUA in infants and young children ages 6 months through 4 years of age. The Pfizer COVID vaccine, which is given in three doses containing three micrograms (one tenth the adult dose) with three weeks between the first and second dose and two months between the second and third dose, was tested in children aged six months to five years old. Although Pfizer reported 80 percent efficacy after the third dose in children under five, the numbers of children evaluated were so tiny that the FDA staff simply commented in its June 15 briefing paper for VRBPAC that, “In these FDA analyses, the immune response to the vaccine for both age groups of children was comparable to the immune response of the older participants.”60
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.61 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.62 Mishandling of the vaccine during any step of the distribution process may result in an ineffective vaccine product. 63 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.64
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.65 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.66 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.67 68
Comirnaty 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.69 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.70
Prior to granting approval of Comirnaty, the FDA declined to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting71 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.”72
On August 23, 2021, Dr. Peter Doshi, Senior Editor of the British Medical Journal (BMJ), expressed concerns regarding the FDA approval in a reference article published in the BMJ Opinion. In his article, Doshi noted that approval of the vaccine was based on a data cut-off date of March 13, 2021, and did not adequately address the concerns of waning vaccine immunity or the efficacy of the vaccine against the Delta variant.73
Doshi noted that the Pfizer data showed that from two months to just less than four months following vaccination, observed vaccine efficacy (VE) had decreased from 96 percent to 90 percent and further decreased to 84 percent from four months to the end date of the data cut off (March 13, 2021). He also noted that the Delta variant likely had little impact on decreased VE as most of the data was collected in the U.S. (77 percent of trial participants were U.S. residents) where Delta was not yet circulating. 74
Data from Israel, which has nearly exclusively administered the Pfizer-BioNTech COVID-19 vaccine, reported a VE of only 64 percent in early July 2021. 75 By late July 2021, the VE had dropped to 39 percent. 76
Additionally, data submitted to the FDA on efficacy involved only seven percent of clinical trial participants who remained blinded up to six months post receipt of the second vaccine dose. By the March 13, 2021 cut off, 93 percent of clinical trial participants had received the vaccine because company officials had begun offering the placebo group vaccination beginning in December of 2020. Doshi noted that no data was submitted to the FDA on VE past 6 months following vaccination, which was the time frame that the Israeli data had reported the vaccine to have a VE of only 39 percent.77
Many in the medical community have stated that the clinical trials have shown the vaccine to be effective against severe COVID-19 illness and would reduce the number of hospitalizations and deaths. Doshi, however, noted that the clinical trials were not designed to study severe disease, that company officials did not report the number of hospitalizations, and there were no COVID-19 related deaths. In the pre-print study, there was one reported case of severe COVID-19 disease in the vaccine group and 30 in the placebo group, but the study did not indicate the number of COVID-19 hospitalizations. There was also a total of three COVID-19 related deaths, one in the vaccine group and two in the placebo group. 78
A study published in November 2021 in the New England Journal of Medicine on the Phase 3 clinical trials of the Pfizer-BioNTech COVID-19 vaccine reported 15 deaths among vaccine recipients and 14 deaths among those who received the placebo. One death in the vaccine group and two deaths in the placebo group were reported to be related to COVID-19. Non-COVID-19 related deaths in the vaccine group included cardiac arrest, sepsis, septic shock, arteriosclerosis, cardiopulmonary arrest, congestive heart failure, chronic obstructive pulmonary disease, lung cancer, and hypertensive heart disease.79 80
The FDA has acknowledged that the long-term effectiveness of Comirnaty remains unknown.81
Pfizer-BioNTech COVID-19 Monovalent Booster Doses
On February 25, 2021, Pfizer-BioNTech 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 six to 12 months after completing the two-dose vaccine series.82
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 vaccine, including a vaccine targeting the South African B.1.351 (Beta) variant.83
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.84
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 had shown the vaccine to be 93.1 percent effective six months after the second dose is administered.85
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). 86 By late July 2021, the vaccine’s effectiveness against the Delta variant in Israel had decreased to only 39 percent.87
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.88
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.89
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.90 However, one month later, the FDA authorized use of a third vaccine dose in persons with immunosuppressive conditions. The CDC’s ACIP recommended use of the third dose in the population on August 13, 2021.91
Pfizer-BioNTech announced on August 16, 2021 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.92
On September 17, 2021, the FDA’s Vaccine and Related Biological Products Advisory Committee (VRBPAC) voted to authorize use under EUA of a third booster dose of the Pfizer-BioNTech mRNA COVID-19 vaccine in persons 65 years of age and older as well as individuals considered at high risk of severe illness. The booster dose for this population was recommended six months after administration of the second dose.93 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.”94
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 at risk of infection due to pre-existing health conditions, they voted against recommending a booster dose for all persons 18 through 64 years whose living or employment situation placed them at high risk of COVID-19 infection. CDC Director Dr. Rochelle Walensky, however, overruled ACIP and issued a recommendation for a booster dose of Pfizer-BioNTech COVID-19 vaccine in all persons 18 and older who worked or lived in high-risk settings.95
A Pfizer funded study 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, reported 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.96
A study published in the New England Journal of Medicine in late October 2021 found that vaccine immunity waned within months of receipt of the second vaccine dose among all age groups. This study was based on data collected in an Israeli database between July 11 and July 31, 2021, for all Israeli residents who were vaccinated prior to June 2021.97
A pre-print retrospective study out of Sweden published on October 25, 2021 found that the Pfizer-BioNTech vaccine progressively waned from a high of 92 percent effectiveness at 15 to 30 days post vaccination with the second vaccine dose, to 47 percent between day 121 and day 180. After day 211, no effectiveness from the vaccine could be detected.98
A booster dose of mRNA COVID-19 vaccine was authorized by the FDA and recommended by the CDC’s ACIP for use in 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). This booster dose was recommended to be administered at least six months after receipt of the second mRNA COVID-19 vaccine dose.99 100 In early January 2022, the interval between the second vaccine dose and booster dose was shortened to five months. In their press release published on January 3, 2022, the FDA stated that “Authorizing booster vaccination to take place at five months rather than six months may therefore provide better protection sooner for individuals against the highly transmissible omicron variant.”101
The FDA authorized a booster dose of Pfizer-BioNTech vaccine for 16 and 17-year olds on December 9, 2021. The authorization in this population was based on data examining the immune responses of 200 individuals between the ages of 18 and 55 years who received a third Pfizer-BioNTech mRNA vaccine about six months following their second dose. According to the FDA, the immune response of the third dose was compared to the immune response examined one month following the second dose in the same individuals. In these individuals, a boost in the immune response was noted.102 A risk-benefit assessment completed by Pfizer-BioNTech was also reviewed by the FDA and was reported to support the booster dose recommendation in this population.103 That day, the booster dose was recommended for use by CDC Director Rochelle Walensky, without a review of the data by ACIP to support use in this population.104
A booster dose of Pfizer-BioNTech COVID-19 vaccine was authorized for use in 12 through 15-year olds in early January 2022 by the FDA and CDC, to be administered five months following the second vaccine dose.105 106 Immunocompromised children aged 5 through 11 years of age were authorized to receive a third dose of the 10mcg COVID-19 mRNA vaccine at least 28 days following the second dose.107
In March 2022, the FDA and CDC authorized a second booster dose for persons 50 years of age and older, to be given at least four months following receipt of the first booster dose. Individuals 12 years of age and older with immunosuppressive conditions were 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 was also authorized, at least four months after the first booster dose.108
In May 2022, the FDA and CDC authorized and recommended a booster dose for all children 5 through 11 years, to be given at least 5 months after the second dose.109 The FDA reported that the EUA for the booster dose was based on data from 67 children aged five through 11 years who received a booster dose given 7 – 9 months after completion of the two-dose primary series. This data showed an increase in antibodies post-vaccination studied but no information was provided on whether the booster dose would prevent COVID-19 illness in this population.110
On August 31, 2022, the FDA revoked the EUA for the use of a monovalent booster dose in persons 12 years and older and recommended use of the newly authorized bivalent mRNA COVID-19 vaccine containing both the original strain and the Omicron Variant (BA.4/BA.5).111 On October 12, 2022, the FDA revoked use of the monovalent booster in all individuals five years and older when they authorized use of the bivalent mRNA COVID-19 vaccine in children five through 11 years.112
In December 2022, the FDA expanded use of the Pfizer-BioNTech bivalent COVID-19 vaccine for use in infants and children six months through four years of age. The authorization was made despite a lack of data on the effectiveness of the vaccine.113 In March 2023, the FDA authorized use of a bivalent booster dose of the Pfizer-BioNTech COVID-19 vaccine in infants and children six months through four years who had completed three primary doses of the Pfizer-BioNTech COVID-19 vaccine.114
Moderna’s COVID-19 Vaccine EUA
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.115
In a press release issued on November 16, 2020, Moderna announced that its experimental mRNA vaccine candidate showed a 94.5 percent efficacy against COVID-19. Company officials reported 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 group.116 117
There was insufficient data on the use of Moderna’s COVID-19 vaccine in persons who were 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.118
Like the Pfizer-BioNTech COVID-19 vaccine trials, Moderna’s Phase 3 clinical trials were not designed to determine whether their vaccine could reduce the impact of COVID-19 illness by decreasing hospitalizations, intensive care stays, or death. Additionally, the vaccines were not studied to assess their ability to halt SARS-CoV-2 virus transmission. The durability of vaccine-acquired immunity is not known and there is limited data on its use in persons who are immunocompromised as well as in children and adolescents.119
A study published in November 2021 in the New England Journal of Medicine that examined the Phase 3 clinical trials noted that there were 17 deaths in vaccine group and 16 deaths in the placebo group. Additionally, study authors reported that one COVID-19 related death occurred among Moderna vaccine recipients and three COVID-19 related deaths occurred among placebo recipients.120 121
In June 2022, the FDA granted an EUA to Moderna for vaccines in infants, children, and teens ages six months through 17 years. According to the FDA, the efficacy of two 25 microgram doses (one quarter of the adult dose) of the Moderna COVID vaccine given about a month apart to children six months to five years old, who had not been previously infected with SARS-CoV-2, was 50.6 percent in preventing symptomatic COVID-19 in a six to 23-month-old age group and 36.8 percent effective in a two to five year old age group. The FDA also reported that two 50 mcg doses (one half of the adult dose) in children six through 11 years and two 100mcg doses in teenagers aged 12 through 17 years induced an immune response similar to adults who received the Moderna COVID-19 mRNA vaccine.122
Moderna’s experimental COVID-19 vaccine must remain frozen between -50°C and -15°C (-58°F and 5°F) and thawed vaccines can’t be refrozen.123 Temperature control issues during product shipment have occurred, resulting in spoiled vaccines.124 125
Moderna has reported that its COVID-19 vaccine appears to offer vaccine-acquired protection against the U.K’s B.1.1.7 (Alpha) variant, but that it had a six-fold reduction against the South African B.1.351(Beta) variant when compared to the initial SARS-CoV-2 virus.126 Company officials have announced the evaluation of several strategies for booster doses to target SARS-CoV-2 variants. 127 128
Moderna’s 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 Moderna mRNA COVID-19 vaccine are interchangeable due to having the same formulation. The FDA also stated that the “Moderna COVID-19 Vaccine remains available under EUA as a two-dose primary series for individuals 18 years of age and older, as a third primary series dose for individuals 18 years of age and older who have been determined to have certain kinds of immunocompromise, and as a single booster dose for individuals 18 years of age and older at least five months after completing a primary series of the vaccine.”129
Spikevax received approval by the FDA based on the Phase 3 trial of vaccine efficacy data collected between July 27, 2020 and March 26, 2021, or when the participant decided that they no longer wanted to be blinded. On average, the median follow-up in the blinded placebo-controlled study was four months following dose two. The Phase 3 study involving 30,415 individuals 18 years and older, with half receiving 2 doses of the vaccine, and half receiving 2 doses of a saline placebo.130
According to the data provided by Moderna to the FDA to support approval for the Spikevax vaccine, there were 55 cases of COVID-19, with two cases classified as serious among the vaccine recipients and 744 cases of COVID-19 with 106 classified as serious in the placebo group during the blinded study period. The vaccine efficacy of Spikevax was reported to be 93.2 percent during this time period.131
There were, however, a total of 32 deaths reported during the blinded Phase 3 clinical trial, with 16 occurring among vaccine recipients and 16 among those who received the placebo. One COVID-19 death was reported among vaccine recipients and three COVID-19 deaths were reported in the placebo group. The remaining deaths that occurred during the clinical trial were reported as being unrelated to vaccination.132 In the open-label phase of the trial, by May 4, 2021, there were 12 deaths reported. Eight deaths occurred among individuals who received the Moderna vaccine and three deaths occurred among persons who initially received the placebo but chose to receive the Moderna vaccine when offered. Only one death occurred in the placebo group. All deaths, however, were reported as being unrelated to vaccination by clinical trial investigators.133
The vaccine was not evaluated for its effectiveness against the Omicron variant, even though this variant was the predominant circulating strain at the time of FDA approval.134
Moderna Monovalent Vaccine Booster Doses
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.135
The CDC and FDA issued a joint statement on July 8, 2021, and reported that a booster dose was not required but stated that they were monitoring the data and would inform the public on the use of booster doses as needed.136
One month later, on August 12, 2021, the FDA authorized the use of a third mRNA vaccine dose in persons with certain immunosuppressive conditions such as those with a history of solid organ transplant. One day later, the CDC’s ACIP approved use of the third dose in this population. According to data presented at the August 13, 2021 ACIP meeting, the mRNA vaccine was reported to be between 59 and 72 percent effective in this population.137
According to a pre-peer review study conducted by researchers from the Mayo Clinic and nference, a data analytics company, by July 2021, the Moderna COVID-19 vaccine was reported to be only 76 percent. This study was conducted during a time when approximately 70 percent of the case were reported as being of the Delta variant.138
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 were recommending that the third dose be administered eight months following receipt of the second COVID-19 booster dose.139 Leading health officials, however, reported that review of the application to support the use of a third Moderna vaccine dose would 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.”140
The FDA authorized use of a 50mcg booster dose (half dose) on October 20, 2021, to be administered six months following receipt of the second vaccine dose.141 In a press release issued on October 21, 2021, the CDC announced that this booster dose was recommended for all persons 65 years and older, for persons 18 years and older at risk of severe COVID-19 illness, and in persons 18 years and older work or live in a setting that places them at high risk of exposure to SARS-CoV-2.142
According to the FDA: 143
“To support the authorization for emergency use of a single booster dose of the Moderna COVID-19 Vaccine, the FDA analyzed immune response data from 149 participants 18 years of age and older from the original clinical studies who received a booster dose at least 6 months after their second dose and compared it to the immune responses of 1,055 study participants after completing their two-dose series. The antibody response of the 149 participants against SARS-CoV-2 virus 29 days after a booster dose of the vaccine demonstrated a booster response.”
A booster dose of mRNA COVID-19 vaccine was authorized by the FDA and recommended by the CDC’s ACIP for use in 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) to be given at least six months following receipt of the second mRNA COVID-19 vaccine dose.144 145 In January 2022, the CDC shortened the interval time for the third dose to five months.146
In March 2022, the FDA and CDC authorized a second booster dose for persons 50 years of age and older, to be given at least four months following receipt of the first booster dose. Immunocompromised individuals were 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 could also be given at least four months after the first booster dose.147
On August 31, 2022, the FDA revoked the EUA for the Moderna monovalent mRNA COVID-19 vaccine in persons 18 years and older and recommended that this population receive a booster dose of a bivalent mRNA vaccine at least two months after completion of the primary series or most recent booster dose.148 On October 12, 2022, the EUA for the Moderna monovalent mRNA COVID-19 was revoked for use in person six years and older when the bivalent mRNA COVID-19 vaccine was authorized for use in children and teens.149
Reformulated Booster Doses
In June 2022, the FDA’s VRBPAC meet to discuss the “future framework” plan for COVID-19 vaccines. This plan, considered similar to the current flu vaccine strategy, would allow for all future reformulations of the COVID-19 vaccine to bypass any additional clinical trials due to their similarity to current vaccines.150 The committee voted in favor of adding the Omicron BA.4/5 spike protein to the current vaccine to create a booster dose for use by early to mid-fall 2022.151
One of the committee members who voted against the booster dose reformulation, Dr. Paul Offit, expressed concern over a lack of data to support the recommendation. In an interview, Offit noted:152
“There are potentially billions of dollars at stake to transform a vaccine from the ancestral strain to a new bivalent strain including these Omicron-specific boosters, without clear and compelling evidence that it’s actually going to improve the outcome we care about most which is protection against severe disease.”
Bivalent mRNA COVID-19 Vaccine (Original Strain & Omicron Variant)
On August 31, 2022, the FDA authorized a single dose of a newly reformatted mRNA COVID-19 vaccine containing the original Wuhan strain and the BA.4 and BA.5 Omicron variant manufactured by Pfizer-BioNTech in individuals 12 years of age and older. This vaccine was recommended to be administered two months following the completion of the primary series or most recent booster dose. Additionally, the FDA also authorized use of a bivalent mRNA COVID-19 vaccine manufactured by Moderna that also contained the original Wuhan strain and the BA.4 and BA.5 Omicron variant.153
No human trials of this bivalent mRNA COVID-19 vaccine prior to the FDA issuing the EUA. Instead, the FDA authorized its use based on data that showed a boost in immune responses against all Omicron variants in mice. The FDA also reported that the authorization was also based on data provided by the manufacturer on a bivalent COVID-19 vaccine containing the original strain and the Omicron BA.1 strain. This data was presented at the June 2022 VRBPAC meeting that reviewed data to support the use of a reformatted COVID-19 vaccine. The committee, however, requested that the reformatted vaccine contain the BA.4 and BA.5 Omicron, to better target the current circulating strain.154 155
On September 1, 2022, the CDC’s ACIP voted in favor of recommending the bivalent mRNA COVID-19 vaccine for all persons 12 and older despite a lack of human data to support its effectiveness.156 In October 2022, the FDA authorized use of the bivalent Pfizer-BioNTech mRNA COVID-19 vaccine for use in children five years and older and the Moderna bivalent mRNA COVID-19 vaccine for use in children six years and older.157
In December 2022, the FDA expanded use of the Moderna bivalent COVID-19 vaccine for use in infants and children six months through five years of age. The authorization was made despite a lack of data on the effectiveness of the vaccine.158
Efficacy of COVID-19 mRNA vaccines
In February 2021, a study questioning the efficacy of COVID-19 vaccines expressed concerns regarding the absence of data on absolute risk reduction in the Pfizer-BioNTech and Moderna COVID-19 vaccine clinical trials.159
According to this study, the Pfizer-BioNTech COVID-19 vaccine showed an absolute risk reduction of 0.7 percent (95% CI 0.59% to 0.83%) and the study author, Ronald Brown, reported that 142 people (95% CI 122 to 170) would need to be vaccinated to prevent one case of COVID-19. The Moderna COVID-19 vaccine showed an absolute risk reduction of 1.1 percent (95% CI 0.97% to 1.32%) and 88 individuals (95% CI 76 to 104) would need to be vaccinated to prevent one COVID-19 case.
Brown concluded by noting that:
“A critical appraisal of phase III clinical trial data for the Pfizer/BioNTech vaccine BNT162b2 and Moderna vaccine mRNA-1273 shows that absolute risk reduction measures are very much lower than the reported relative risk reduction measures. Yet, the manufacturers failed to report absolute risk reduction measures in publicly released documents. As well, the U.S FDA Advisory Committee (VRBPAC) did not follow FDA published guidelines for communicating risks and benefits to the public, and the committee failed to report absolute risk reduction measures in authorizing the BNT162b2 and mRNA-1273 vaccines for emergency use. Such examples of outcome reporting bias mislead and distort the public’s interpretation of COVID-19 mRNA vaccine efficacy and violate the ethical and legal obligations of informed consent.”
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.160 The CDC, however, gave a preferential recommendation to mRNA vaccines on December 16, 2021 due to the risk of TTS following vaccination.161 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.162
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.163 The vaccine, however, was reported to be only 42 percent effective in persons over the age of 60 who have underlying health conditions.164
Janssen/Johnson & Johnson’s experimental vaccine, Ad26.COV2.S (or JNJ-78436725), is a non-replicating viral vector vaccine that uses AdVac® and PER.C6® technologies.165 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.166 167 PER.C6 are proprietary cells owned by Janssen Pharmaceutical that were developed in 1985 from retinal cells of an 18-week-old aborted fetus.168
According to a press release issued on January 29, 2021 by the National Institutes of Health:169
“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.170
On October 20, 2021, the FDA authorized use of a booster dose of the Janssen/Johnson & Johnson COVID-19 vaccine in all persons 18 years of age and older at least two months after receipt of the initial vaccine dose.171 However, in December 2021, the CDC revised its recommendations for a booster dose of the vaccine due to the risk of thrombosis with thrombocytopenia syndrome (TTS) following vaccine. Instead, the CDC recommended that persons who received the Janssen/Johnson & Johnson COVID-19 vaccine should receive a booster dose of an mRNA COVID-19 vaccine.172
In September 2022, the CDC updated its recommendations and stated that all persons who received a primary series of Janssen/ Johnson & Johnson COVID-19 vaccine get a booster dose of a bivalent mRNA COVID-19 (Pfizer-BioNTech or Moderna) vaccine at least two months following receipt of the primary series. No data was provided to support the safety or effectiveness of this recommendation.173 174
On July 13, 2022, the FDA issued an EUA to Novavax for its COVID-19 vaccine for use in adults 18 years and older who have not previously received a dose of COVID-19. According to the FDA, the vaccine was reported to be 90.4 percent effective at preventing mild, moderate, or severe COVID-19 illness. In persons 65 years and older, the vaccine was reported to be 78.6 percent effective. Clinical trials, however, were conducted prior to the emergence of the Delta and Omicron variants, and information on the vaccine’s effectiveness against these strains is not known.175
In September 2022, the CDC recommended that all persons who received a primary series of Novavax COVID-19 vaccine get a booster dose of a bivalent mRNA COVID-19 (Pfizer-BioNTech or Moderna) vaccine at least two months following receipt of the primary series. No data was provided to support the safety or effectiveness of this recommendation.176 177 A booster dose of Novavax vaccine in persons 18 years and older who are unable to receive an mRNA COVID-19 vaccine, or in adults 18 years and older who would otherwise not receive a COVID-19 vaccine was authorized for use by the FDA on October 19, 2022. This booster dose is recommended to be given at least six months after completion of the primary COVID-19 vaccine series or most recent vaccine dose.178
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.179
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.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 COVID-19 vaccine is estimated to have an efficacy of about 60 percent.181 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.182
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.183
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."184
In July 2021, AstraZeneca announced plans to seek full approval of the vaccine, rather than a fast-tracked status, in U.S.185 As of March 19, 2023, the vaccine is not available in U.S.
Global Impact of COVID-19 Vaccines
An article published on September 30, 2021 in the European Journal of Epidemiology reported that vaccination has had no impact on COVID-19 rates. According to the published data that looked at COVID-19 cases in 68 countries and 2947 U.S. counties reported:186
At the country-level, there appears to be no discernable relationship between percentage of population fully vaccinated and new COVID-19 cases in the last 7 days. In fact, the trend line suggests a marginally positive association such that countries with higher percentage of population fully vaccinated have higher COVID-19 cases per 1 million people.
Study authors recommended that strategies focusing on vaccination as a primary method of mitigating COVID-19 be re-evaluated.
A pre-print study pending peer review conducted primarily by Danish researchers and published in April 2022 found that mRNA COVID-19 vaccines have had no impact on reducing all-cause mortality in randomized controlled trials (RCTs). Scientists involved in the research found that mRNA COVID-19 vaccines were only protective against fatal infection, while adenovirus vaccines such as the Janssen/Johnson & Johnson vaccine "were associated with lower overall mortality and lower non-accident, non-COVID-19 mortality." The paper also found that while mRNA COVID-19 vaccines reduced COVID-19 deaths, the vaccine increased cardiovascular deaths, but that the data for either was not statistically significant.187
COVID-19 Vaccines and Mortality Rates
An analysis conducted for The Health 202 in the fall of 2022 reported a higher mortality rate in COVID-19 vaccinated individuals than those who were unvaccinated. According to the study, in August 2022, 58 percent of deaths occurred in individuals who were either vaccinated or vaccinated and boosted. This was an increase from earlier in the year, when an estimated 42 percent of deaths occurred among vaccinated people.188
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.
1 U.S. Food and Drug Administration. FDA Takes Action on Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants. Sept. 11, 2023.
3 U.S. Food and Drug Administration. Moderna COVID-19 Vaccine Sheet for Healthcare Providers. Sept. 11, 2023.
5 U.S. Food and Drug Administration. Pfizer-BioNTech COVID-19 Vaccine Fact Sheet for Healthcare Providers. Sept. 11, 2023.
6 Bernstein H. What Is the Difference between Vaccine Efficacy and Vaccine Effectiveness?. Childrens Hospital of Philadelpia July 2021.
7 US Centers for Disease Control and Prevention. How do vaccine effectiveness studies differ from vaccine efficacy studies?. Jan 6, 2023.
8 Katella K. What’s the Difference Between COVID-19 Vaccine Efficacy and Effectiveness?. Yale Medicine Nov. 5, 2021.
9[9 Shrestha NK, Burke PC, Nowalski AS. et al. Risk of Coronavirus Disease 2019 (COVID-19) among Those Up-to-Date and Not Up-to-Date on COVID-19 Vaccination by US CDC Criteria. MedRxiv Sept. 14, 2023.
10 Ko L, Malet G, Chang LL. et al. COVID-19 Infection Rates in Vaccinated and Unvaccinated Inmates: A Retrospective Cohort Study. Cureus Sept. 4, 2023; 15(9): e44684.
11 Tartof SY, Frankland TB, Slezak JM et al. Receipt of BNT162b2 Vaccine and COVID-19 Ambulatory Visits in US Children Younger Than 5 Years. JAMA Sept. 15, 2023.
12 Piper G. 'Scientifically bizarre': Research, CDC data undermine COVID vax recommendations for kids, new moms. Just the News Sept. Sept. 20, 2023.
13 Cohn BA, Cirillo PM, Murphy CC, et al. SARS-CoV-2 vaccine protection and deaths among US veterans during 2021. Science Jan 21, 2022; 375(6578):331-336.
14 Lyngse FP, Mortensen LH, Denwood MJ, et al. Household transmission of the SARS-CoV-2 Omicron variant in Denmark. Nat Commun 2022.
15 Buchan SA, Chung H, Brown KA, et al. Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes. JAMA Netw Open. 2022.
16 Ferdinands JM, Rao S, Dixon BE, et al. Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022. MMWR August 2021; 71(7);255–263.
17 Altarawneh HN, Chemaitelly H, Ayoub HH. Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. N Engl J Med. July 7, 2022; 387:21-34.
18 Lin DY. Effects of Vaccination and Previous Infection on Omicron Infections in Children. N Engl J Med. Sept. 7, 2022; 387:1141-1143.
19 Tseng HF, Ackerson BK, Bruxvoort KJ. Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Nat Commun. Jan 12, 2023.
20 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
21 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
22 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
23 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
24 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
25 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
26 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
27 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
28 Link-Gelles R. Updates to COVID-19 Vaccine Effectiveness (VE) in the U.S. Presentation to the CDC’s Advisory Committee on Immunization Practices Meeting. Sept. 12, 2023.
29 Hunter PR. Brainard J. Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of ‘real-world’ vaccination outcomes from Israel. medRxiv Feb. 3, 2021.
30 Lopez Bernal J, Andrews N, Gower C et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ May 13, 2021;373:n1088.
31 Chemaitelly H, Tang P, Hasan MR, et al. Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar. N Engl J Med Dec 9, 2021;385(24):e83.
32 Subramanian SV, Kumar A. Increases in COVID-19 are unrelated to levels of vaccination across 68 countries and 2947 counties in the United States. Eur J Epidemiol. Sep 30, 2021; 36(12): 1237–1240.
33 Piper G. Foreign research finds Pfizer, Moderna COVID vaccines don't reduce all-cause mortality. Just The News Apr. 27, 2022.