First Two FDA-Authorized COVID-19 Vaccines Rarely Cause Severe Allergic Reactions

Health Letter, March 2021

By Michael Carome, M.D.

vaccines
Image: Viacheslav Lopatin/Shutterstock.com

On Dec. 11, 2020, the Food and Drug Administration (FDA) granted an emergency use authorization (EUA) for the COVID-19 vaccine developed by Pfizer and BioNTech for individuals aged 16 and older. One week later, the agency granted an EUA for a COVID-19 vaccine developed by Moderna and the National Institutes of Health (NIH) for adults aged 18 and older.

Within a few days of the Pfizer-BioNTech COVID-19 vaccine being rolled out across the U.S., the media reported several cases of a severe allergic reaction known as anaphylaxis in recipients of this vaccine shortly after the first dose was administered. Soon thereafter, reports emerged of similar severe allergic reactions in recipients of the Moderna-NIH COVID-19 vaccine. Fortunately, data recently published jointly by the Centers for Disease Control and Prevention (CDC) and the FDA provide reassurance that anaphylaxis occurs only rarely following the first dose of these vaccines.

Data from clinical trials

Both the Pfizer-BioNTech and the Moderna-NIH COVID-19 vaccines — each administered in two doses separated by three and four weeks, respectively — were tested in large, well-designed, placebo-controlled clinical trials. The trial for the former vaccine enrolled approximately 44,000 subjects and for the latter about 30,400 subjects, with half of the subjects in each trial receiving the active vaccine and the other half a placebo. These trials are ongoing and will follow subjects for up to two years.

Both vaccines were found to be remarkably effective in preventing COVID-19: 95% for the Pfizer-BioNTech vaccine and 94% for the Moderna-NIH vaccine, levels that far exceeded the FDA’s threshold of 50% effectiveness for a COVID-19 vaccine to qualify for an EUA. Importantly, the effectiveness of the vaccines was similar across age groups, genders, and racial and ethnic groups. Both vaccines also appear to be highly effective in preventing severe COVID-19.

From a safety perspective, the clinical trials demonstrated that both the Pfizer-BioNTech and Moderna-NIH COVID-19 vaccines caused generally short-term adverse effects, such as pain, redness and swelling at the injection site, fatigue, headaches, muscle and joint pains, fever, and chills. Adverse effects were more common after the second vaccine dose. Notably, during the clinical trials, only one subject who received the Pfizer-BioNTech vaccine experienced an episode of anaphylaxis, whereas no such adverse events occurred in subjects who received the Moderna-NIH vaccine.

Given the calamitous number of COVID-19 cases, hospitalizations and deaths and based on a review of the available safety and effectiveness data regarding the Pfizer-BioNTech and Moderna-NIH vaccines that were made public in December, Public Citizen’s Health Research Group concluded that the benefits of both vaccines outweigh their risks. We therefore agreed with the agency’s decisions to grant EUAs for these vaccines.

The CDC and FDA data

The CDC and FDA have been closely monitoring reports of adverse events in recipients of the COVID-19 vaccines that have been submitted to the Vaccine Adverse Event Reporting System (VAERS). VAERS is a national early warning surveillance system to detect possible safety problems in vaccines licensed for use in the U.S. The system is co-managed by both agencies.

In January, the CDC and FDA jointly published two reports in the CDC’s Morbidity and Mortality Weekly Reports (MMWR) that detailed analyses of VAERS data on allergic reactions, including anaphylaxis, after the first dose of the Pfizer-BioNTech COVID-19 and Moderna-NIH COVID-19 vaccines.

Pfizer-BioNTech COVID-19 vaccine

The first MMWR report, published online on Jan. 6, summarized data on severe allergic reactions that occurred after the first dose of the Pfizer-BioNTech COVID-19 vaccine. As of Dec. 23, 2020, approximately 1.9 million people in the U.S. had received the first dose of the vaccine, and 4,393 reports of adverse events post-vaccination had been submitted to VAERS.

Among these reports, 175 were identified as possible cases of severe allergic reaction. After further review, 21 cases were determined to be anaphylaxis (a rate of 11 cases per million doses), 86 were judged to be non-anaphylaxis allergic reactions and 61 were considered non-allergic events.

Of the 21 anaphylaxis events, 17 occurred in people with a documented history of allergies or allergic reactions, seven of whom had a history of anaphylaxis. The median interval between vaccination and onset of anaphylaxis symptoms was 13 minutes, with a range of two to 150 minutes. Follow-up information was available for 20 of the anaphylaxis cases, and all had recovered or been discharged home.

Moderna-NIH COVID-19 vaccine

The second MMWR report, published online on Jan. 22, presented data on severe allergic reactions after the first dose of the Moderna-NIH COVID-19 vaccine. As of Jan. 10, 2021, approximately four million people in the U.S. had received the first dose of the vaccine, and 1,266 reports of adverse events post-vaccination had been submitted to VAERS.

Among these reports, 108 were identified as possible cases of severe allergic reaction. After further review, 10 cases were determined to be anaphylaxis (a rate of 2.5 cases per million doses), 47 were judged to be non-anaphylaxis allergic reactions and 47 were considered non-allergic events.

Of the 10 anaphylaxis events, nine occurred in people with a documented history of allergies or allergic reactions, five of whom had a history of anaphylaxis. The median interval between vaccination and onset of anaphylaxis symptoms was eight minutes, with a range of one to 45 minutes. Follow-up information was available for eight of the anaphylaxis cases, and all had recovered or been discharged home.

Recommendations

In light of the VAERS data provided by the CDC and FDA, our conclusion remains that the benefits of both vaccines outweigh their risks.

Although there remain important unanswered questions — such as how long the effectiveness of the vaccines lasts, whether they diminish community spread of the coronavirus and whether they cause yet unidentified rare serious adverse effects — we encourage readers eligible to receive these vaccines under the EUAs to get vaccinated when they become available. However, anyone who experiences an allergic reaction to the first dose of the Pfizer-BioNTech or Moderna-NIH COVID-19 vaccine should not receive an additional dose of either vaccine.

Importantly, until we know more about the effectiveness of these vaccines, vaccinated individuals should continue to wear face masks and follow social-distancing guidelines to contain the pandemic.