Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine | Vaccination | JAMA | JAMA Network
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January 21, 2021

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

Author Affiliations
  • 1Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 2Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
JAMA. 2021;325(8):780-781. doi:10.1001/jama.2021.0600

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.

Table.  Characteristics of Cases of Anaphylaxis (N = 21) Following Receipt of Pfizer-BioNTech COVID-19 Vaccine Reported to the Vaccine Adverse Events Reporting System (VAERS), December 14-23, 2020a
Characteristics of Cases of Anaphylaxis (N = 21) Following Receipt of Pfizer-BioNTech COVID-19 Vaccine Reported to the Vaccine Adverse Events Reporting System (VAERS), December 14-23, 2020a

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

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Article Information

Corresponding Author: Tom Shimabukuro, MD, MPH, MBA, Immunization Safety Office, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329 (ayv6@cdc.gov).

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.

References
1.
FDA. Fact sheet for healthcare providers administering vaccine (vaccination providers): Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). Revised January 2021. Accessed January 17, 2021. https://www.fda.gov/media/144413/download
2.
Oliver  SE, Gargano  JW, Marin  M,  et al.  The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 Vaccine—United States, December 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(50):1922-1924. doi:10.15585/mmwr.mm6950e2 PubMedGoogle ScholarCrossref
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 Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine—United States, December 14–23, 2020.   MMWR Morb Mortal Wkly Rep. Published January 6, 2021. doi:10.15585/mmwr.mm7002e1Google Scholar
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McNeil  MM, DeStefano  F.  Vaccine-associated hypersensitivity.   J Allergy Clin Immunol. 2018;141(2):463-472. doi:10.1016/j.jaci.2017.12.971 PubMedGoogle ScholarCrossref
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Shimabukuro  TT, Nguyen  M, Martin  D, DeStefano  F.  Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS).   Vaccine. 2015;33(36):4398-4405. PubMedGoogle ScholarCrossref
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Rüggeberg  JU, Gold  MS, Bayas  JM,  et al.  Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data.   Vaccine. 2007;25(31):5675-5684. doi:10.1016/j.vaccine.2007.02.064 PubMedGoogle ScholarCrossref
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Rossen  LM, Branum  AM, Ahmad  FB,  et al.  Excess deaths associated with COVID-19, by age and race and ethnicity—United States, January 26–October 3, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(42):1522-1527. doi:10.15585/mmwr.mm6942e2 PubMedGoogle ScholarCrossref
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CDC. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. Updated January 6, 2021. Accessed January 17, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
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CDC. Interim considerations: preparing for the potential management of anaphylaxis after COVID-19 vaccination. Updated December 31, 2020. Accessed January 18, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/anaphylaxis-management.html
10.
Vaccine Adverse Event Reporting System: report an adverse event to VAERS. Accessed January 18, 2021. https://vaers.hhs.gov/reportevent.html
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    1 Comment for this article
    EXPAND ALL
    Anaphylaxis to Ingredients?
    Job Harenberg, MD, Professor of Medicine | Heidelberg University
    The authors must be congratulated for timely publishing about side effects of the Pfizer/BioNtech COVID-19 vaccine. Mild, moderate, severe, and fatal side effects of vaccines occur in specific population cohorts regardless of origin, production, and administration. Anaphylactic reactions to vaccines are known, and incidents occurred with the Pfizer/BioNtech COVID-19 vaccine less frequently in size of decimal compared to the illness itself requiring intensive care unit treatment.

    Anaphylactic reactions to drugs and vaccines may also occur to ingredients used to improve absorption and metabolism. Some of the 1.89 million patients may also have developed anaphylactic reactions to the ingredients
    reducing the absolute number of reported adverse reactions to the Pfizer-BioNtech COVID-19 vaccine itself. Obviously, ingredients differ between COVID-19 vaccines and adverse reactions can be expected to differ too. Additional insights into ingredients-mediated adverse events may further improve the safety of COVID-19 vaccines.

    Job Harenberg, MD, Emeritus Professor of Medicine, Heidelberg University
    Managing Director Doasense GmbH, Germany
    j.harenberg@doasense.de
    CONFLICT OF INTEREST: Managing Director, Founder DOASENSE (doasense.de)
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