COVID vaccine-associated allergic reactions

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

The SARS-CoV-2 virus has incited a global pandemic leading to profound loss of human life and tremendous economic and social upheaval. In late 2020, the FDA issued emergency use authorizations (EUAs) for mRNA vaccines produced by Pfizer-BioNTech and Moderna that were found to be highly effective in Phase 3 trials at preventing COVID-19. The active ingredient in both vaccines is nucleoside-modified mRNA encoding the SARS-CoV-2 spike protein. Both vaccines exhibited a favorable safety profile, with most side effects being mild to moderate in severity and including pain, swelling, and redness at the injection site, headache, fatigue, fever, chills, nausea, myalgia, arthralgia, and lymphadenopathy. However, within days of administration of the vaccines to healthcare workers in both the United States (US) and United Kingdom (UK), multiple reports of severe allergic reactions emerged. As of January 18, 2021, the overall rate of anaphylaxis to the mRNA COVID-19 vaccines was estimated at 4.7 cases per million doses administered for the Pfizer-BioNTech vaccine and 2.5 cases per million doses administered for the Moderna vaccine. This rate of anaphylaxis is higher than that reported for vaccines in general, which is 1.31 (95% CI, 0.90-1.84) cases per million vaccine doses, using similar criteria for defining anaphylaxis. This may be a gross underestimation - a large academic medical center recently reported the rate of anaphylactic reactions to the Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines among their employees to be 166 times greater than the historical combined anaphylaxis event rate for all vaccinations. At this point, we have no information about the antigen or underlying mechanisms responsible for triggering allergic reactions to the COVID-19 mRNA vaccines. As a result, there is no diagnostic test that can be used to reliably predict whether a given individual is at risk for having an allergic reaction to these vaccines. This has resulted in considerable confusion and lack of consensus in the field of allergy on how to advise patients who reacted to the mRNA COVID-19 vaccines. Individuals who experience an allergic reaction (of any severity) to the first dose of the mRNA COVID-19 vaccines are currently contraindicated from receiving a second dose, according to guidelines from the Centers for Disease Control and Prevention (CDC). Presumably they will also not be eligible to receive any boosters that may be recommended over time, or future vaccines using the mRNA platform. Additionally, individuals who had an allergic reaction to the mRNA COVID-19 vaccines have a precaution to receiving the Johnson and Johnson COVID-19 vaccine. Hesitancy to receive the Johnson and Johnson vaccine has also increased given the addition of a warning that women less than 50 are at higher risk of a rare but serious blood clot disorder called thrombosis with thrombocytopenia syndrome (TTS). Of note, the vast majority of allergic reactions to the mRNA COVID-19 vaccines have occurred in this same demographic group. For these reasons, a better understanding of the mechanisms responsible for allergic reactions to the mRNA COVID-19 vaccines is critically needed in order to reassure the public and to provide evidence-based guidance on who can safely receive these vaccines, including a second dose in those individuals who experienced a reaction to the first dose. We have therefore developed a clinical trial to assess the safety of administering the Pfizer-BioNTech mRNA COVID-19 vaccine to individuals 18-69 years of age who experienced a systemic allergic reaction to the first dose of either the Moderna or Pfizer-BioNTech mRNA COVID-19 vaccines. This will be a single-site study that will be conducted in the Intensive Care Unit (ICU) at the NIH Clinical Center (CC). The primary objective of the study is to assess the proportion of participants who develop a systemic allergic reaction to the Pfizer-BioNTech vaccine after previously demonstrating a systemic allergic reaction to the first dose of either the Moderna or Pfizer-BioNTech mRNA COVID-19 vaccines. A broad range of mechanistic studies will also be performed to learn more about the mechanisms underlying these reactions.