Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine — United States, December 21, 2020–January 10, 2021

As of January 20, 2021, a total of 24 135 690 cases of coronavirus disease 2019 (COVID19) and 400 306 associated deaths had been reported in the United States (https://covid.cdc.gov/covid datatrack er/#cases_cases per10 0klas t7days). On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Moderna COVID19 vaccine administered as 2 doses, 1 month apart to prevent COVID19. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of Moderna COVID19 vaccine.1 As of January 10, 2021, a reported 4 041 396 first doses of Moderna COVID19 vaccine had been administered in the United States, and reports of 1266 (0.03%) adverse events after receipt of Moderna COVID19 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 lifethreatening 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 COVID19 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 min (range = 1– 45 min). Among eight persons with followup 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 COVID19 vaccine during December 21, 2020– January 10, 2021, in the United States. CDC has issued updated interim clinical considerations for use of mRNA COVID19 vaccines currently authorized in the United States3 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 anxietyrelated, 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– 1day 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 COVID19 vaccine (2 465 411

vaccine. 1  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.  of first doses were administered in women. 5  The findings in this report are subject to at least two limitations.
First, analyses of passive surveillance data include reporting biases, both underreporting because of lack of awareness or compliance with reporting requirements and reporting guidance, as well as stimulated reporting related to increased awareness from media or other public information sources. Second, incomplete information in reports and potential data lags because of processing times might result in an undercount of cases, and lags in reporting for vaccine doses administered might underestimate denominator data.
However, reporting efficiency to VAERS for clinically severe adverse events is believed to be high. 9 It is reasonable to expect that diagnosis and reporting of an acute and clinically severe condition reporting adverse events after immunization to VAERS at https:// vaers.hhs.gov/repor tevent.html.

Investigators from the Clinical Immunization Safety Assessment
Project.

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* 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. acces sdata.fda.gov/scrip ts/cdrh/cfdoc s/cfcfr/ cfrse arch.cfm?fr =312.32 ¶ https://www.aaaai.org/about -aaaai/ newsr oom/aller gy-stati stics