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

United States, December 21, 2020-January 10, 2021

Morbidity and Mortality Weekly Report. 2021;70(4):125-129. 

In This Article

Abstract and Introduction

Introduction

As of January 20, 2021, a total of 24,135,690 cases of coronavirus disease 2019 (COVID-19) and 400,306 associated deaths had been reported in the United States (https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days). On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Moderna COVID-19 vaccine administered as 2 doses, 1 month apart to prevent COVID-19. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of Moderna COVID-19 vaccine.[1] As of January 10, 2021, a reported 4,041,396 first doses of Moderna COVID-19 vaccine had been administered in the United States, and reports of 1,266 (0.03%) adverse events after receipt of Moderna COVID-19 vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS). Among these, 108 case reports were identified for further review as possible cases of severe allergic reaction, including anaphylaxis. Anaphylaxis is a life-threatening allergic reaction that occurs rarely after vaccination, with onset typically within minutes to hours.[2] Among these case reports, 10 cases were determined to be anaphylaxis (a rate of 2.5 anaphylaxis cases per million Moderna COVID-19 vaccine doses administered), including nine in persons with a documented history of allergies or allergic reactions, five of whom had a previous history of anaphylaxis. The median interval from vaccine receipt to symptom onset was 7.5 minutes (range = 1–45 minutes). Among eight persons with follow-up information available, all had recovered or been discharged home. Among the remaining case reports that were determined not to be anaphylaxis, 47 were assessed to be nonanaphylaxis allergic reactions, and 47 were considered nonallergic adverse events. For four case reports, investigators have been unable to obtain sufficient information to assess the likelihood of anaphylaxis. This report summarizes the clinical and epidemiologic characteristics of case reports of allergic reactions, including anaphylaxis and nonanaphylaxis allergic reactions, after receipt of the first dose of Moderna COVID-19 vaccine during December 21, 2020–January 10, 2021, in the United States. CDC has issued updated interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States[3] and interim considerations for preparing for the potential management of anaphylaxis.[4]

Using methods previously described,[5] CDC and FDA identified reports of suspected anaphylaxis in VAERS, the national passive surveillance (i.e., spontaneous reporting) system for monitoring adverse events after immunization.[6] CDC physicians screened VAERS reports describing suspected severe allergic reactions and anaphylaxis and applied Brighton Collaboration case definition criteria for anaphylaxis*.[7] After initial screening, reports with sufficient evidence to suggest anaphylaxis were followed up by collecting information from medical records and through direct outreach to health care facilities and treating health care providers, and, in some cases, vaccine recipients. Physician reviewers classified all initially identified case reports as anaphylaxis or not anaphylaxis and used clinical judgment to further categorize reports that were considered not anaphylaxis as nonanaphylaxis allergic reactions or nonallergic adverse events. Nonallergic adverse events, mostly vasovagal (e.g., fainting or the sensation of fainting) or suspected anxiety-related, were excluded from the final analyses. Anaphylaxis and nonanaphylaxis allergic reaction cases with symptom onset occurring later than the day after vaccination (i.e., outside the 0–1-day risk window) were also excluded because of the difficulty in clearly attributing allergic reactions with onset later than this to vaccination.

During December 21, 2020–January 10, 2021, the administration of 4,041,396 first doses of Moderna COVID-19 vaccine (2,465,411 to females [61%], 1,450,966 to males [36%], and 125,019 to persons whose sex was not recorded [3%]) was reported to CDC. During the same period, reports of 1,266 (0.03%) adverse events after receipt of the first dose of Moderna COVID-19 vaccine had been submitted to VAERS. Among these, 108 case reports were identified for further review as possible cases of severe allergic reaction, including anaphylaxis, based on descriptions of signs and symptoms; 10 of these reports, all describing events in females, met the Brighton Collaboration case definition criteria for anaphylaxis (Table 1), corresponding to an initial estimated rate of 2.5 anaphylaxis cases per million first Moderna COVID-19 vaccine doses administered. The median age of persons with anaphylaxis was 47 years (range = 31–63 years). The median interval from vaccine receipt to symptom onset was 7.5 minutes (range = 1–45 minutes); nine patients had onset within 15 minutes, and one had onset after 30 minutes (Figure). In all 10 reports, patients received epinephrine as part of initial emergency treatment; the route of administration was confirmed or presumed to be intramuscular based on the description of treatment and the clinical course of the event as documented in the VAERS report. Six patients were hospitalized (including five in intensive care, four of whom required endotracheal intubation), and four were treated in an emergency department; eight patients with follow-up information available are known to have been discharged home or had recovered at the time of report to VAERS. No deaths from anaphylaxis were reported after receipt of Moderna COVID-19 vaccine. Nine of the 10 anaphylaxis case reports included a patient history of allergies or allergic reactions, including to drugs (six), contrast media (two), and foods (one); five patients had experienced an episode of anaphylaxis in the past, none of which was associated with receipt of a vaccine (Table 2). No geographic clustering of anaphylaxis cases was observed, and the cases occurred after receipt of doses from multiple vaccine lots. At the time of this publication, despite follow-up efforts, investigators have been unable to obtain sufficient information to assess the likelihood of anaphylaxis in four of the initial 108 suspected cases reported.

Figure.

Minutes from vaccine receipt to onset of anaphylaxis (A)* and nonanaphylaxis allergic reactions (B) after receipt of the first dose of Moderna COVID-19 vaccine — Vaccine Adverse Events Reporting System (VAERS), United States, December 21, 2020–January 10, 2021
Abbreviation: COVID-19 = coronavirus disease 2019.
*The interval from vaccine receipt to symptom onset was >30 minutes for one anaphylaxis case (45 minutes).
The interval from vaccine receipt to symptom onset was ≥60 minutes for three nonanaphylaxis patients who had a documented history of allergies or allergic reactions at 60, 90, and 98 minutes and for four who did not have a documented history of allergies or allergic reactions (60 minutes, 10 hours, 20 hours, and 24 hours). The interval from vaccine receipt to symptom onset was missing in two case reports, both of which documented a history of allergies or allergic reactions. Four cases of nonanaphylaxis allergic reactions with symptom onset occurring later than the day after vaccination (i.e., outside of the 0–1-day risk window) were excluded from the final analysis.

Among the 43 cases of nonanaphylaxis allergic reaction after receipt of Moderna COVID-19 vaccination with symptom onset within the 0–1-day risk window, 26 (60%) were classified as nonserious.§ Commonly reported symptoms included pruritus, rash, itchy sensations in the mouth and throat, sensations of throat closure, and respiratory symptoms. The median patient age was 43 years (range = 22–96 years), and 39 (91%) of the reported reactions occurred in women. The median interval from vaccine receipt to symptom onset was 15 minutes (range = <1 minute–24 hours); in 30 (73%) cases, onset occurred within 30 minutes, in 11 cases, onset occurred after 30 minutes, and for two cases, time of onset was missing. For 26 (60%) case reports, a past history of allergies or allergic reactions, mostly to foods and drugs, was documented (Figure).

*Brighton level 1 represents the highest level of diagnostic certainty that a reported case is indeed a case of anaphylaxis; levels 2 and 3 represent successively lower levels of diagnostic certainty. Level 4 is a case reported as "anaphylaxis" but that does not meet the Brighton Collaboration case definition. Level 5 is a case that was neither reported as anaphylaxis nor meets the case definition.
Anaphylaxis and nonanaphylaxis allergic reaction cases with symptom onset occurring later than the day after vaccination (i.e., outside of the 0–1-day risk window) were excluded because of the difficulty in clearly attributing allergic reactions with onset outside this risk window to vaccination.
§Four of the initial 47 nonanaphylaxis allergic reactions were excluded from the final analysis. Based on the Code of Federal Regulations, a serious adverse event is defined if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly, or birth defect. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=312.32

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