Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 2020-January 18, 2021 | Allergy and Clinical Immunology | JAMA | JAMA Network
[Skip to Navigation]
Sign In
Views 338,672
Citations 0
JAMA Insights
February 12, 2021

Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 2020-January 18, 2021

Author Affiliations
  • 1Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 2Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
JAMA. Published online February 12, 2021. doi:10.1001/jama.2021.1967

In December 2020, the US Food and Drug Administration (FDA) issued Emergency Use Authorizations for 2 mRNA-based vaccines for prevention of coronavirus disease 2019 (COVID-19): Pfizer-BioNTech COVID-19 vaccine (EUA issued December 11; 2 doses, 3 weeks apart) and Moderna COVID-19 vaccine (EUA issued December 18; 2 doses, 1 month apart). Shortly after each authorization, the Advisory Committee on Immunization Practices issued interim recommendations for use.1,2

Following implementation of vaccination, cases of anaphylaxis after administration of the Pfizer-BioNTech and Moderna vaccines began to be reported.3,4 Anaphylaxis is a life-threatening allergic reaction that can occur after vaccination, with onset typically within minutes to hours.5 The initial estimated reporting rates for anaphylaxis in the US were 11.1 cases per million doses administered of the Pfizer-BioNTech vaccine (December 14-23, 2020) and 2.5 cases per million doses administered of the Moderna vaccine (December 21, 2020-January 10, 2021).3,4 Since these early estimates were generated, millions more doses of both vaccines have been administered and safety monitoring has detected additional cases of anaphylaxis. This analysis updates the reporting rates of anaphylaxis in individuals following receipt of either the Pfizer-BioNTech or Moderna vaccine.

The Vaccine Adverse Event Reporting System (VAERS), the national passive surveillance (spontaneous reporting) system for adverse events after immunization,6 captured notifications and reports of suspected anaphylaxis following vaccination. Physicians at the Centers for Disease Control and Prevention (CDC) evaluated these reports and applied the Brighton Collaboration case definition for anaphylaxis to classify cases.7

During December 14, 2020 through January 18, 2021, a total of 9 943 247 doses of the Pfizer-BioNTech vaccine and 7 581 429 doses of the Moderna vaccine were reported administered in the US (CDC unpublished data, February 2021). CDC identified 66 case reports received by VAERS that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2 or 3): 47 following Pfizer-BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered. Cases occurred after receipt of doses from multiple vaccine lots. Characteristics of reported cases of anaphylaxis following these vaccines are described in the Table.

Table.  Characteristics of Reported Cases of Anaphylaxis Following Receipt of Pfizer-BioNTech (9 943 247 Doses) and Moderna (7 581 429 Doses) COVID-19 Vaccines—Vaccine Adverse Events Reporting System (VAERS), US, December 14, 2020-January 18, 2021
Characteristics of Reported Cases of Anaphylaxis Following Receipt of Pfizer-BioNTech (9 943 247 Doses) and Moderna (7 581 429 Doses) COVID-19 Vaccines—Vaccine Adverse Events Reporting System (VAERS), US, December 14, 2020-January 18, 2021

CDC physician reviewers concluded that the clinical characteristics of anaphylaxis cases following both vaccines were similar. Furthermore, there were no apparent clinical differences between anaphylaxis cases with symptom onset within 30 minutes and those with symptom onset after 30 minutes (a 15-minute postvaccination observation period is recommended for all persons and a 30-minute period is recommended for those with a history of certain allergic reactions).8 Common signs and symptoms in anaphylaxis cases were generalized urticaria, diffuse erythematous rash, angioedema, respiratory and airway obstruction symptoms, and nausea. Twenty-one (32%) of the 66 case reports noted a prior episode of anaphylaxis from other exposures; prior exposures included vaccines (rabies, influenza A[H1N1], seasonal influenza, unspecified), contrast media (gadolinium-based, iodine-based, unspecified intravenous), unspecified infusions, sulfa drugs, penicillin, prochlorperazine, latex, walnuts, unspecified tree nuts, jellyfish stings, and unspecified exposures.

In 61 (92%) of the anaphylaxis cases, patients received epinephrine as part of emergency treatment. All 66 persons were treated in health care settings; 34 (52%) were treated in an emergency department and 32 (48%) were hospitalized (including 18 in intensive care, 7 of whom required endotracheal intubation). As determined by medical record review and follow-up with treating health care facilities and clinicians, of the 7 patients who required endotracheal intubation, median time to symptom onset was 6 minutes (range, <1-45 minutes), with all but one patient having onset within 11 minutes. All 7 of those intubated received epinephrine, 6 received corticosteroids, and 5 received antihistamines; facial, tongue, or laryngeal angioedema was present in 4 of these patients; and hospitalization ranged from 1 to 3 days. Sixty-one individuals (92%) with follow-up information available are known to have been discharged from care or had recovered at the time of report to VAERS. No deaths from anaphylaxis after vaccination with either product were reported.

Continued safety monitoring of mRNA COVID-19 vaccines in the US has confirmed that anaphylaxis following vaccination is a rare event, with rates of 4.7 cases/million Pfizer-BioNTech vaccine doses administered and 2.5 cases/million Moderna vaccine doses administered, based on information through January 18, 2021. When considered in the context of morbidity and mortality from COVID-19,9 the benefits of vaccination far outweigh the risk of anaphylaxis, which is treatable. Because of the acute, life-threatening nature of anaphylaxis, immediate epinephrine administration is indicated for all cases. CDC guidance on use of mRNA COVID-19 vaccines8 and management of anaphylaxis is available.10 All facilities administering COVID-19 vaccines should have the necessary supplies and trained medical personnel available to manage anaphylaxis.

Back to top
Article Information

Corresponding Author: Tom Shimabukuro, MD, MPH, MBA, Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30329 (tshimabukuro@cdc.gov).

Published Online: February 12, 2021. doi:10.1001/jama.2021.1967

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 the CDC. Mention of a product or company name is for identification purposes only and does not constitute endorsement by the CDC.

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.
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
2.
Oliver  SE, Gargano  JW, Marin  M,  et al.  The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020.   MMWR Morb Mortal Wkly Rep. 2021;69(5152):1653-1656. doi:10.15585/mmwr.mm695152e1PubMedGoogle ScholarCrossref
3.
Shimabukuro  T, Nair  N.  Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine.   JAMA. Published online January 21, 2021. doi:10.1001/jama.2021.0600PubMedGoogle Scholar
4.
CDC COVID-19 Response Team; Food and Drug Administration.  Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020-January 10, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(4):125-129. doi:10.15585/mmwr.mm7004e1PubMedGoogle ScholarCrossref
5.
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
6.
Shimabukuro  TT, Nguyen  M, Martin  D, DeStefano  F.  Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS).   Vaccine. 2015;33(36):4398-4405. doi:10.1016/j.vaccine.2015.07.035 PubMedGoogle ScholarCrossref
7.
Rüggeberg  JU, Gold  MS, Bayas  JM,  et al; Brighton Collaboration Anaphylaxis Working Group.  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
8.
Rossen  LM, Branum  AM, Ahmad  FB, Sutton  P, Anderson  RN.  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
9.
CDC. COVID-19 vaccination: interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. Updated January 21, 2021. Accessed February 9, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
10.
CDC. COVID-19 vaccination: interim considerations: preparing for the potential management of anaphylaxis after COVID-19 vaccination. Updated December 31, 2020. Accessed February 9, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/anaphylaxis-management.html
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    2 Comments for this article
    EXPAND ALL
    Additional clarity
    Hristos Dagres, MD, MPH | Self-Employed
    This report provides valuable information regarding possibly life-threatening events. I would like to kindly offer some suggestions that could improve the clarity of the provided information in the future:

    - The table could include treatment options (epinephrine, intubation) in order to present potential difference of severity between the 2 vaccines
    - It's important to distinguish between the events after the 1st or the 2nd dose; the hypothesis is that the rate and/or severity of anaphylaxis may be higher after the 2nd dose. However, we need to know the number of doses administered for each category, therefore it could
    be better to present the details of anaphylaxis after the 1st or 2nd dose in separate tables.
    - The upper age is 63 years for both vaccines; is this because of limited number of doses administered to elderly patients or could this suggest lower immunogenicity in elderly patient and, thus, possibly lower efficacy?
    - The rate of Pfizer-BioNTech vaccine events is nearly 60% lower than it was initially reported. Are there any possible explanations for this? Could it be due to improvements in vaccine production, or a potential evidence of under-reporting?

    Lastly, I would like to ask whether cases of lack of efficacy are reported in the VAERS system and if there are plans to present these cases in the future. Given that now there should be a significant number of persons with completed immunization, it would be interesting to see the number and distribution of potential cases of lack of efficacy.
    CONFLICT OF INTEREST: I was employed on behalf of a Swiss Pharmaceutical Company, in Drug Development/ Oncology
    READ MORE
    Gender disparity
    Thomas Moore, MD | Boston University School of Medicine (emeritus)
    One of the most striking things in the table is that the vast majority of cases of anaphylaxis occurred in women. This was true of both vaccines (95% overall). I am aware that, in general, anaphylaxis is more common in women, but not to this extent. The authors do not comment on this gender disparity. Perhaps there is something different about these vaccines or mRNA vaccines in general. Certainly worth watching as our experience with these vaccines evolves.
    CONFLICT OF INTEREST: None Reported
    ×