key: cord-0804668-w2k03p5n
authors: Rodriguez-Nava, Guillermo; Egoryan, Goar; Trelles-Garcia, Daniela Patricia; Yanez-Bello, Maria Adriana; Murguia-Fuentes, Ricardo
title: Disproportionality Analysis of Anaphylactic Reactions after Vaccination with mRNA COVID-19 Vaccines in the United States
date: 2021-04-08
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2021.04.004
sha: f6123575c4caed24c309bb421b8e659328733ad8
doc_id: 804668
cord_uid: w2k03p5n

nan

One year after the emergence of the novel coronavirus SARS-CoV-2 that causes the coronavirus disease 2019 , the United States Food and Drug Administration (FDA) granted two Emergency Use Authorizations (EUA) for two novel mRNA COVID-19 vaccines.

Reports of acute hypersensitivity reactions in the real world after EUA are creating anxiety among potential vaccine recipients and may delay achieving universal vaccination (1) . Although the Centers for Disease Control and Prevention (CDC) and the FDA jointly monitor vaccine adverse reactions through a variety of surveillance systems such as the Vaccine Adverse Event

Reporting System (VAERS) or the CDC's Vaccine Safety Datalink (2), local health care professionals also play an essential role in monitoring vaccine safety, reporting to VAERS, and providing factual and up-to-date information to increase vaccine acceptance.

In a previous report, we have demonstrated the simplicity and versatility of the CDC Wideranging Online Data for Epidemiologic Research (CDC WONDER) in conjunction with proportional reporting ratios (PRRs) to obtain up-to-date information about vaccine safety evaluating the reports submitted to the VAERS. No disproportionate reporting of severe adverse drug reactions (ADRs), including anaphylaxis, was found to be associated with the use of the MMR vaccine compared to all other vaccines over 30 years (3) . In this report, we used the CDC WONDER Web interface and PRRs to assess whether the number of anaphylaxis cases reported in the VAERS database secondary to the two currently available mRNA COVID-19 vaccines is significantly different from all other vaccines.

We used the CDC WONDER interface to retrieve data from the VAERS national database of all spontaneous ADRs and anaphylaxis reports, including -anaphylactic reaction‖ or -anaphylactic shock‖ from the -Symptoms‖ tab in the site request form, of individuals 18 years of age and older vaccinated with the Pfizer-BioNTech or Moderna vaccines since they were made available to the public in the U.S. and all ADRs and anaphylaxis reports of individuals 18 years of age and older vaccinated with all other vaccines available between December 1, 2020, to cases/million doses administered and 2.5 cases/million doses administered, respectively (2, 8) .

In a recent update, after a total of 9 943 247 doses of the Pfizer-BioNTech vaccine and 7 581 429 doses of the Moderna vaccine, the CDC identified 66 case reports that met the case definition criteria for anaphylaxis: 47 following Pfizer-BioNTech vaccine, for an updated reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a stable reporting rate of 2.5 cases/million doses administered. No deaths from anaphylaxis after vaccination with either vaccine were reported (9) . Anaphylaxis after vaccination is indeed a rarely reported event, with an overall reported rate of 1.3 cases/million doses administered for all licensed vaccines (10) .

The process of scrutinizing spontaneous ADR data for hazards is known as data mining and signal generation. Browsing the CDC WONDER website and applying PRRs is a relatively simple and straightforward disproportionality analysis method for signal generation based on comparing reporting proportions in a contingency table between the study drug and all drugs in the spontaneous reporting database combined (4, 5) . However, this method has some significant caveats. First, the VAERS data consist of unverified reports of health events, both minor and severe, that occur after vaccination, and these reports may include incomplete, inaccurate, coincidental, and unverified information. Second, the request form in the CDC WONDER interface only includes broad and non-specific terms for the search engine; hence, some submitted reports may not meet the criteria for anaphylaxis, overestimating the database numbers. Finally, PRRs and Chi-squared values are measures of association, not causality.

Establishing causal relationships between vaccines and adverse events requires additional scientific investigation. Ultimately, this method cannot be used for comparative drug safety analysis beyond basic hypothesis generation (5) . Despite these limitations, the CDC WONDER interface and calculation of PRRs are a valuable aid to signal generation from spontaneous ADR data that provide clinicians and allergists versatile tools for quick evidence-based decisionmaking after developing new vaccines and treatments. 

Pfizer's vaccine raises allergy concerns

Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine

MMR Vaccine Adverse Drug Reactions Reports in the CDC WONDER System, 1989-2019. Open Forum Infect Dis

Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports

Can Disproportionality Analysis of Postmarketing Case Reports be Used for Comparison of Drug Safety Profiles?

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID

Reports of Anaphylaxis After Receipt of mRNA COVID-19

Anaphylaxis after vaccination reported to the Vaccine Adverse Event Reporting System