Acute Allergic Reactions to mRNA COVID-19 Vaccines
March 8th, 2021
Kimberly G. Blumenthal, MD, MSc; Lacey B. Robinson, MD, MPH; Carlos A. Camargo Jr, MD, DrPH; et al. Erica S. Shenoy, MD, PhD; Aleena Banerji, MD; Adam B. Landman, MD; Paige Wickner, MD, MPH
JAMA. Published online March 8, 2021. doi:10.1001/jama.2021.3976
Anaphylaxis to the mRNA COVID-19 vaccines is currently estimated to occur in 2.5 to 11.1 cases per million doses, largely in individuals with a history of allergy.(1) Allergic concerns contribute to vaccine hesitancy; we investigated acute allergic reaction incidence after more than 60,000 mRNA COVID-19 vaccine administrations.
We prospectively studied Mass General Brigham (MGB) employees who received their first dose of an mRNA COVID-19 vaccine (12/16/2020-2/12/2021, with follow-up through 2/18/2021) (eMethods in the Supplement). For 3 days after vaccination, employees completed symptom surveys through a multipronged approach including email, text message, phone, and smartphone application links. Acute allergic reaction symptoms solicited included itching, rash, hives, swelling, and/or respiratory symptoms (eAppendix in the Supplement).
To identify anaphylaxis, allergists/immunologists reviewed the electronic health records of employees (1) reporting 2 or more allergy symptoms, (2) described as having an allergic reaction in MGB safety reports, (3) logged by the on-call MGB allergy/immunology team supporting employee vaccination, and (4) referred to MGB allergy/immunology. Episodes were scored using the Brighton Criteria2 and the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria.3 Confirmed anaphylaxis required meeting at least 1 of these 2 sets of criteria.
We described characteristics and outcomes of anaphylaxis cases. We calculated incidence rates and 95% CIs of self-reported acute allergic reactions and confirmed anaphylaxis, using vaccine administrations as the denominator. We compared frequencies using χ2 tests, considering a 2-sided P value of .05 statistically significant. Analyses were conducted in SAS version 9.4. This study was approved by the MGB Human Research Committee with a waiver of informed consent.
Of 64. 900 employees who received their first dose of a COVID-19 vaccine, 25. 929 (40%) received the Pfizer-BioNTech vaccine and 38. 971 (60%) received the Moderna vaccine. At least 1 symptom survey was completed by 52 805 (81%).
Acute allergic reactions were reported by 1365 employees overall (2.10% [95% CI, 1.99%-2.22%]), more frequently with the Moderna vaccine compared with Pfizer-BioNTech (2.20% [95% CI, 2.06%-2.35%] vs 1.95% [95% CI, 1.79%-2.13%]; P = .03, Table 1). Anaphylaxis was confirmed in 16 employees (0.025% [95% CI, 0.014%-0.040%]): 7 cases from the Pfizer-BioNTech vaccine (0.027% [95% CI, 0.011%-0.056%]) and 9 cases from the Moderna vaccine (0.023% [95% CI, 0.011%-0.044%]) (P = .76).
Individuals with anaphylaxis were a mean (SD) age of 41 (13) years, and 15 (94%) were female (Table 2); 10 (63%) had a prior allergy history and 5 (31%) had an anaphylaxis history. Mean time to anaphylaxis onset was 17 minutes (SD, 28; range, 1-120). One patient was admitted to intensive care, 9 (56%) received intramuscular epinephrine, and all recovered. Three employees, with prior anaphylaxis history, did not seek care.
In this prospective cohort of health care employees, 98% did not have any symptoms of an allergic reaction after receiving an mRNA COVID-19 vaccine. The remaining 2% reported, some allergic symptoms; however, severe reactions consistent with anaphylaxis occurred at a rate of 2.47 per 10 000 vaccinations. All individuals with anaphylaxis cases recovered without shock or endotracheal intubation.
The incidence rate of confirmed anaphylaxis in this study is larger than that reported by the Centers for Disease Control and Prevention based on passive spontaneous reporting methods (0.025-0.11/10 000 vaccinations).(1) However, the overall risk of anaphylaxis to an mRNA COVID-19 vaccine remains extremely low and largely comparable to other common health care exposures.(4) Although cases were clinically compatible with anaphylaxis, the mechanism of these reactions is unknown.
Most of the vaccine recipients with anaphylaxis had allergy histories, with 31% having prior anaphylaxis. However, given that approximately 5% of adults have severe food allergy histories (5) and 1% of adults have severe drug allergy histories,6 this MGB employee cohort likely included almost 4000 individuals with severe food or medication allergy histories who were safely vaccinated.
Limitations of this study include the use of self-reported data. However, cohort participants were largely health care workers, and therefore self-report data reliability may be high. The use of vaccine administrations as the denominator for allergic reaction incidence may have resulted in some inaccuracy. Although study methods might have missed cases of potential anaphylaxis, comprehensive prospective surveillance methods were used, and symptom survey alone captured 81% of all vaccinated employees. A northeastern US cohort may not be generalizable.
Robert Gorter, MD, PhD commentary:
This study tried to collect data of acute allergic reactions during the very first three days. Many allergic reactions (even death) can occur many days later (like Idiopathic Thrombocytopenia (ITP) and Kawasaki Syndrom).
The Vaccine Adverse Event Reporting System (VAERS) is a national vaccine safety surveillance program run by CDC and the Food and Drug Administration (FDA). VAERS serves as an early warning system to detect possible safety issues with U.S. vaccines by collecting information about adverse events (possible side effects or health problems) that occur after vaccination.
VAERS was created in 1990 in response to the National Childhood Vaccine Injury Act. If any health problem happens after vaccination, anyone – doctors, nurses, vaccine manufacturers, and any member of the general public – can submit a report to VAERS.
According to “Electronic Support for Public Health–Vaccine Adverse Event Reporting System,” a research project in the USA which focused on improving the quality of physician adverse vaccine event detection and reporting to the national Vaccine Adverse Event Reporting System (VAERS), fewer than 1% of all vaccine adverse events are ever reported in the USA and in Europe likely very similar.
Corresponding Author: Kimberly G. Blumenthal, MD, MSc, The Mongan Institute, Massachusetts General Hospital, 100 Cambridge St, 16th Floor, Boston, MA 02114 (firstname.lastname@example.org).
Funding/Support: This work was supported by NIH K01 AI125631 and the Massachusetts General Hospital Department of Medicine Transformative Scholar Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH nor Massachusetts General Hospital.
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