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. The FDA has now approved two 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. The overall rate of anaphylaxis to the mRNA COVID-19 vaccines is currently estimated at approximately 2.5-10 cases per million doses administered, which is higher than that reported for vaccines in general, 1.31 (95% CI, 0.90-1.84) cases per million vaccine doses, using similar criteria for defining anaphylaxis. At this point, we do not know 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. Current CDC guidelines contraindicate subsequent doses of the mRNA vaccine in patients with a severe allergic reaction or a non-severe immediate allergic reaction to a prior dose of mRNA vaccine or known history of allergy to the components of the vaccine and recommend vaccination with alternative platforms. Presumably these individuals will also not be eligible to receive any future vaccines using the mRNA platform, which may have significant consequences as this technology is being utilized both for other infectious diseases (influenza, HIV, RSV, Herpes, CMV and Zika are already undergoing early trials) and cancer (studies ongoing in treatment of solid tumors and melanoma in conjunction with immunotherapy). For these reasons, a better understanding of the mechanisms responsible for allergic reactions to the mRNA COVID 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 and booster dose in those individuals who experienced a reaction to the first dose. In FY22, we have continued enrollment on our 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 is a single-site study that is being 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 (Consortium for Food Allergy Research (CoFAR)) grade 2 reaction and above regardless of tryptase, and CoFAR grade 1 with elevated tryptase (1.2 X baseline plus 2 ng/mL) to the Pfizer-BioNTech vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase (1.2 X baseline plus 2 ng/mL) to the first dose of either the Moderna or Pfizer-BioNTech mRNA COVID-19 vaccines. Individuals who experience no or only a mild allergic reaction to the second dose of the vaccine have the opportunity to receive a booster dose 5 months later. A broad range of mechanistic studies are also being performed to learn more about the mechanisms underlying these reactions.