Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020
Early Release / January 6, 2021 / 70

CDC COVID-19 Response Team; Food and Drug Administration
Discussion
Early safety monitoring of the Pfizer-BioNTech COVID-19 vaccine has detected 21 cases of anaphylaxis after reported administration of 1,893,360 first doses of Pfizer-BioNTech COVID-19 vaccine (11.1 cases per million vaccine doses administered) as well as cases of less severe nonanaphylaxis allergic reactions, based on U.S. data for December 14–23, 2020. Most (86%) anaphylaxis cases had symptom onset within 30 minutes of vaccination, and most persons with anaphylaxis (81%) had a history of allergies or allergic reactions, including some with previous anaphylaxis events; up to 30% of persons in the general population might have some type of allergy or history of allergic reactions.¶ Most (90%) reported anaphylaxis cases after receipt of Pfizer-BioNTech COVID-19 vaccine occurred in women, although 64% of the vaccine doses administered with sex of recipient recorded were given in women. Whereas a female predominance has been previously observed in a review of immediate hypersensitivity reports to VAERS after influenza A(H1N1) vaccine (8), the current finding could be impacted by the observation that more women than men had received a first dose of Pfizer-BioNTech COVID-19 vaccine during the analytic period. Anaphylaxis is potentially life-threatening and requires immediate treatment (5). Based on early safety monitoring, anaphylaxis after the Pfizer-BioNTech COVID-19 vaccine appears to be a rare event; however, comparisons of anaphylaxis risk with that associated with non-COVID-19 vaccines are constrained at this time by the limited data available this early in the COVID-19 vaccination program. CDC and FDA will continue enhanced monitoring for anaphylaxis among recipients of COVID-19 vaccines.

The findings in this report are subject to at least four limitations. First, the anaphylaxis and nonanaphylaxis allergic reaction case reports were gathered through passive surveillance based on spontaneous reports to VAERS. Spontaneous reporting is subject to reporting biases (including underreporting); however, the reporting efficiency to VAERS for clinically severe adverse events is believed to be high (9). A second potential source of bias arises from stimulated reporting related to increased public and health care provider awareness of a potential safety concern. Thus, it is possible that intense media attention around the national COVID-19 vaccination program and heightened awareness of reports of anaphylaxis have affected vaccine recipient and health care provider behavior and practices, including elevated concern and anxiety, higher index of suspicion for anaphylaxis, and lower threshold for early treatment of suspected cases, thereby resulting in an increase in diagnosis of suspected anaphylaxis and corresponding stimulated above-baseline reporting to VAERS. Third, it is possible that data lags and incomplete reporting of vaccine doses administered might underestimate the denominator (doses administered) relative to the numerator (anaphylaxis cases). If anaphylaxis cases after receipt of COVID-19 vaccine are identified and reported faster than vaccine doses administered are reported, the anaphylaxis rate associated with vaccination might be overestimated. Finally, the focus on the Pfizer-BioNTech COVID-19 vaccine is a function of the timing of product availability and doses administered. Data on the Moderna vaccine, which became available a week later, were limited. Vaccination with Moderna COVID-19 vaccine commenced on December 21, 2020, and through December 23, 2020, an estimated 224,322 first doses of the vaccine had been administered; one report that met the Brighton Collaboration case definition criteria for anaphylaxis had been submitted to VAERS.

Mortality from COVID-19 in populations at high risk is substantial (10), and treatment options are limited. Widespread vaccination against COVID-19 with highly effective vaccines represents an important tool in efforts to control the pandemic. CDC and FDA will continue to monitor for adverse events, including anaphylaxis, after receipt of COVID-19 vaccines and will regularly assess the benefits and risks of vaccination in the context of the evolving epidemiology of the pandemic. Continued monitoring in VAERS and additional monitoring in population-based surveillance systems, such as the CDC’s Vaccine Safety Datalink (https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html), will help to further characterize the risk for anaphylaxis after administration of COVID-19 vaccines. CDC guidance on use of mRNA COVID-19 vaccines and management of anaphylaxis is available (4,5). Specifically, vaccination locations should 1) ensure that necessary supplies are available to manage anaphylaxis, especially sufficient quantities of epinephrine in prefilled syringes or autoinjectors; 2) screen potential vaccine recipients to identify persons with contraindications and precautions (4); 3) implement recommended postvaccination observation periods, either 15 or 30 minutes depending on each patient’s previous history of allergic reactions; 4) ensure that health care providers can recognize the signs and symptoms of anaphylaxis early; and 5) immediately treat suspected anaphylaxis with intramuscular epinephrine; because of the acute, life-threatening nature of anaphylaxis, there are no contraindications to epinephrine administration. Patients experiencing anaphylaxis should be transported to facilities where they can receive appropriate medical care (5). All patients should be instructed to seek immediate medical care if they develop signs or symptoms of an allergic reaction after their observation period ends and they have left the vaccination location. Health care providers can play an important role in vaccine safety by being vigilant in recognizing and reporting adverse events after immunization to VAERS at https://u.to/TYvTGg icon.