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

United States, December 14-23, 2020

Morbidity and Mortality Weekly Report. 2021;70(2):46-51. 

In This Article

Abstract and Introduction

Introduction

As of January 3, 2021, a total of 20,346,372 cases of coronavirus disease 2019 (COVID-19) and 349,246 associated deaths have been reported in the United States. Long-term sequalae of COVID-19 over the course of a lifetime currently are unknown; however, persistent symptoms and serious complications are being reported among COVID-19 survivors, including persons who initially experience a mild acute illness.* On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 vaccine to prevent COVID-19, administered as 2 doses separated by 21 days. On December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine;[1] initial doses were recommended for health care personnel and long-term care facility residents.[2] As of December 23, 2020, a reported 1,893,360 first doses of Pfizer-BioNTech COVID-19 vaccine had been administered in the United States, and reports of 4,393 (0.2%) adverse events after receipt of Pfizer BioNTech COVID-19 vaccine had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Among these, 175 case reports were identified for further review as possible cases of severe allergic reaction, including anaphylaxis. Anaphylaxis is a life-threatening allergic reaction that does occur rarely after vaccination, with onset typically within minutes to hours.[3] Twenty-one cases were determined to be anaphylaxis (a rate of 11.1 per million doses administered), including 17 in persons with a documented history of allergies or allergic reactions, seven of whom had a history of anaphylaxis. The median interval from vaccine receipt to symptom onset was 13 minutes (range = 2–150 minutes). Among 20 persons with follow-up information available, all had recovered or been discharged home. Of the remaining case reports that were determined not to be anaphylaxis, 86 were judged to be nonanaphylaxis allergic reactions, and 61 were considered nonallergic adverse events. Seven case reports were still under investigation. 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 Pfizer-BioNTech COVID-19 vaccine during December 14–23, 2020, in the United States. CDC has issued updated interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States[4] and interim considerations for preparing for the potential management of anaphylaxis.[5] In addition to screening for contraindications and precautions before administering COVID-19 vaccines, vaccine locations should have the necessary supplies available to manage anaphylaxis, should implement postvaccination observation periods, and should immediately treat persons experiencing anaphylaxis signs and symptoms with intramuscular injection of epinephrine.[4,5]

CDC and FDA received notification of suspected anaphylaxis cases through multiple channels, including direct outreach by health care providers and public health officials and reports to VAERS, the national passive surveillance (spontaneous reporting) system for adverse events after immunization, which is jointly operated by CDC and FDA.[6] All notifications of suspected anaphylaxis that came to the attention of CDC or FDA were also captured in VAERS. CDC physicians screened VAERS reports describing suspected severe allergic reactions and anaphylaxis and applied Brighton Collaboration case definition criteria,[7] which use combinations of symptoms to define levels of diagnostic certainty to identify cases with sufficient evidence to warrant further assessment for anaphylaxis. 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 which does not meet the Brighton Collaboration case definition. Level 5 is a case that was neither reported as anaphylaxis nor meets the case definition. Reports with sufficient evidence to suggest anaphylaxis were followed up by direct outreach, including telephoning contacts listed in the VAERS report to gather additional clinical details (e.g., health care facilities and treating health care providers, and, in some cases, vaccine recipients) and collecting medical records. Physician reviewers also used their clinical judgment to categorize reports that were considered not anaphylaxis as nonanaphylaxis allergic reactions or nonallergic adverse events. 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 (i.e., outside of 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. CDC and FDA conducted joint review sessions to discuss and adjudicate cases. Because the FDA EUA for the Moderna COVID-19 vaccine was received 1 week later than that for the Pfizer-BioNTech vaccine (i.e., on December 18, 2020), and the Moderna vaccine was only available beginning December 21, this report focuses on the Pfizer-BioNTech COVID-19 vaccine. An assessment of adverse events reported after receipt of the Moderna COVID-19 vaccine will be forthcoming.

During December 14–23, 2020, after administration of 1,893,360 first doses of Pfizer-BioNTech COVID-19 vaccine (1,177,527 doses in females, 648,327 doses in males, and 67,506 doses missing sex), reports of 4,393 (0.2%) adverse events after receipt of the vaccine had been submitted to VAERS. Among these, 175 case reports were identified for further review as possible cases of severe allergic reaction, including anaphylaxis, based on descriptions of signs and symptoms; 21 of these reports met the Brighton Collaboration case definition criteria for anaphylaxis, corresponding to an initial estimated rate of 11.1 cases per million doses administered. All reports were Brighton levels 1 or 2 (Table 1). The median age of persons with anaphylaxis was 40 years (range = 27–60 years), and 19 (90%) cases occurred in females. The median interval from vaccine receipt to symptom onset was 13 minutes (range = 2–150 minutes); 15 (71%) patients had onset within 15 minutes, three (14%) within 15 to 30 minutes, and three (14%) after 30 minutes (Figure). In 19 of 21 (90%) reports, patients were treated with epinephrine as part of therapy; one patient received subcutaneous epinephrine and the remaining 18 were confirmed or presumed to have received intramuscular epinephrine based on the report. Four (19%) patients were hospitalized (including three 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 report to VAERS. No deaths from anaphylaxis were reported after receipt of Pfizer-BioNTech COVID-19 vaccine. 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; seven (33%) patients had experienced an episode of anaphylaxis in the past, including one after receipt of a rabies vaccine and another after receipt of an influenza A(H1N1) 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 report, investigators have been unable to obtain sufficient information to confirm or rule out anaphylaxis in seven cases despite follow-up efforts; these cases remain under investigation.

Figure.

Interval (minutes) from vaccine receipt to onset of anaphylaxis (A)* and nonanaphylaxis allergic reactions (B) after receipt of Pfizer-BioNTech COVID-19 vaccine — Vaccine Adverse Events Reporting System, United States, December 14–23, 2020
Abbreviation: COVID-19 = coronavirus disease 2019.
*The interval from vaccine receipt to symptom onset was >30 minutes for three anaphylaxis cases (34, 54, and 150 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 90, 96, and 180 minutes and for three who did not have a documented history of allergies or allergic reactions (105 minutes, 137 minutes, and 20 hours). Interval from vaccine receipt to symptom onset was missing for four patients with a history of allergies or allergic reactions and for seven without such history. Three 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.

During the same period, VAERS identified 83 cases of nonanaphylaxis allergic reaction after Pfizer-BioNTech COVID-19 vaccination with symptom onset within the 0–1-day risk window, 72 (87%) of which were classified as nonserious.§ Commonly reported symptoms included pruritus, rash, itchy and scratchy sensations in the throat, and mild respiratory symptoms. The median patient age was 43 years (range = 18–65 years), and 75 (90%) reported reactions occurred in women. The median interval from vaccine receipt to symptom onset was 12 minutes (range = <1 minute–20 hours); in 61 (85%) cases, onset occurred within 30 minutes, in 11 cases, onset occurred after 30 minutes, and for 11 cases, time of onset was missing. For 56 (67%) case reports, a past history of allergies or allergic reactions was documented (Table 2) (Figure).

*https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/late-sequelae.html.
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. Three of the initial 86 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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