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On December 11, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine, administered as 2 doses separated by 21 days.1 Shortly after, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use.2 Following implementation of vaccination, reports of anaphylaxis after the first dose of the Pfizer-BioNTech COVID-19 vaccine emerged.3 Anaphylaxis is a life-threatening allergic reaction that occurs rarely after vaccination, with onset typically within minutes to hours.4
Notifications and reports of suspected severe allergic reactions and anaphylaxis following vaccination were captured in the Vaccine Adverse Event Reporting System (VAERS), the national passive surveillance (spontaneous reporting) system for adverse events after immunization.5 Physicians at the US Centers for Disease Control and Prevention (CDC) evaluated these reports and applied Brighton Collaboration case definition criteria6 to classify case reports as anaphylaxis or not anaphylaxis. Nonallergic adverse events, mostly vasovagal or anxiety-related, were excluded from the analysis. Anaphylaxis and nonanaphylaxis allergic reaction cases with symptom onset occurring later than the day after vaccination were also excluded because of the difficulty in clearly attributing allergic reactions with delayed onset after vaccination. Because the Moderna COVID-19 vaccine was only available beginning December 21, 2020, this article focuses on the Pfizer-BioNTech COVID-19 vaccine.
During December 14 to 23, 2020, after administration of a reported 1 893 360 first doses of Pfizer-BioNTech COVID-19 vaccine (1 177 527 in women, 648 327 in men, and 67 506 with sex of recipient not reported),3 CDC identified 21 case reports submitted to VAERS that met Brighton Collaboration case definition criteria for anaphylaxis (Table), corresponding to an estimated rate of 11.1 cases per million doses administered. Four patients (19%) were hospitalized (including 3 in intensive care), and 17 (81%) were treated in an emergency department; 20 (95%) are known to have been discharged home or had recovered at the time of the report to VAERS. No deaths from anaphylaxis were reported.
Median interval from vaccine receipt to symptom onset was 13 minutes (range, 2-150 minutes); 15 patients (71%) had onset within 15 minutes; 18 (86%) had onset within 30 minutes.3 The most common symptoms and signs were urticaria, angioedema, rash, and a sense of throat closure. Seventeen (81%) of 21 patients with anaphylaxis had a documented history of allergies or allergic reactions, including to drugs or medical products, foods, and insect stings; 7 (33%) had experienced an episode of anaphylaxis in the past, including one after receipt of rabies vaccine and another after receipt of influenza A(H1N1) vaccine (Table). During the same period, VAERS identified 83 cases of nonanaphylaxis allergic reactions after Pfizer-BioNTech COVID-19 vaccination.3 Commonly reported symptoms in nonanaphylaxis allergic reactions included pruritus, rash, itchy and scratchy sensations in the throat, and mild respiratory symptoms.
Mortality from COVID-19 in populations at high risk is substantial,7 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 guidance on use of mRNA COVID-19 vaccines8 and management of anaphylaxis is available.9 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; (3) implement recommended postvaccination observation periods, either 15 or 30 minutes depending on each patient’s previous history of allergic reactions; (4) ensure that physicians and other health care professionals can recognize 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 to receive appropriate medical care. 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. Clinicians have an important role in vaccine safety monitoring by being vigilant in recognizing and reporting adverse events to VAERS.10
Corresponding Author: Tom Shimabukuro, MD, MPH, MBA, Immunization Safety Office, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329 (firstname.lastname@example.org).
Published Online: January 21, 2021. doi:10.1001/jama.2021.0600
Conflict of Interest Disclosures: None reported.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC or FDA. Mention of a product or company name is for identification purposes only and does not constitute endorsement by CDC or FDA.
Additional Contributions: We thank investigators from the CDC COVID-19 Response Team; the FDA Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research; and the Clinical Immunization Safety Assessment Project.
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Shimabukuro T, Nair N. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine. JAMA. 2021;325(8):780–781. doi:10.1001/jama.2021.0600
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