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Meta-Analysis
. 2022 Apr 1;182(4):376-385.
doi: 10.1001/jamainternmed.2021.8515.

Risk of Second Allergic Reaction to SARS-CoV-2 Vaccines: A Systematic Review and Meta-analysis

Derek K Chu  1   2   3   4 , Elissa M Abrams  5 , David B K Golden  6 , Kimberly G Blumenthal  7 , Anna R Wolfson  7 , Cosby A Stone Jr  8 , Matthew S Krantz  8 , Marcus Shaker  9   10 , Matthew Greenhawt  11
Affiliations
Meta-Analysis

Risk of Second Allergic Reaction to SARS-CoV-2 Vaccines: A Systematic Review and Meta-analysis

Derek K Chu et al. JAMA Intern Med. .

Abstract

Importance: Vaccination against SARS-CoV-2 is a highly effective strategy to prevent infection and severe COVID-19 outcomes. The best strategy for a second dose of vaccine among persons who had an immediate allergic reaction to their first SARS CoV-2 vaccination is unclear.

Objective: To assess the risk of severe immediate allergic reactions (eg, anaphylaxis) to a second dose of SARS-CoV-2 mRNA vaccine among persons with immediate allergic reactions to their first vaccine dose.

Data sources: MEDLINE, Embase, Web of Science, and the World Health Organization Global Coronavirus database were searched from inception through October 4, 2021.

Study selection: Included studies addressed immediate allergic reactions of any severity to a second SARS-CoV-2 vaccine dose in persons with a known or suspected immediate allergic reaction (<4 hours after vaccination) after their first SARS-CoV-2 vaccine dose. Studies describing a second vaccine dose among persons reporting delayed reactions (>4 hours after vaccination) were excluded.

Data extraction and synthesis: Paired reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects models were used for meta-analysis. The GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach evaluated certainty of the evidence.

Main outcomes and measures: Risk of severe immediate allergic reaction and repeated severe immediate allergic reactions with a second vaccine dose. Reaction severity was defined by the reporting investigator, using Brighton Collaboration Criteria, Ring and Messmer criteria, World Allergy Organization criteria, or National Institute of Allergy and Infectious Diseases criteria.

Results: Among 22 studies of SARS-CoV-2 mRNA vaccines, 1366 individuals (87.8% women; mean age, 46.1 years) had immediate allergic reactions to their first vaccination. Analysis using the pooled random-effects model found that 6 patients developed severe immediate allergic reactions after their second vaccination (absolute risk, 0.16% [95% CI, 0.01%-2.94%]), 232 developed mild symptoms (13.65% [95% CI, 7.76%-22.9%]), and, conversely, 1360 tolerated the dose (99.84% [95% CI, 97.09%-99.99%]). Among 78 persons with severe immediate allergic reactions to their first SARS-CoV-2 mRNA vaccination, 4 people (4.94% [95% CI, 0.93%-22.28%]) had a second severe immediate reaction, and 15 had nonsevere symptoms (9.54% [95% CI, 2.18%-33.34%]). There were no deaths. Graded vaccine dosing, skin testing, and premedication as risk-stratification strategies did not alter the findings. Certainty of evidence was moderate for those with any allergic reaction to the first dose and low for those with severe allergic reactions to the first dose.

Conclusions and relevance: In this systematic review and meta-analysis of case studies and case reports, the risk of immediate allergic reactions and severe immediate reactions or anaphylaxis associated with a second dose of an SARS-CoV-2 mRNA vaccine was low among persons who experienced an immediate allergic reaction to their first dose. These findings suggest that revaccination of individuals with an immediate allergic reaction to a first SARS-CoV-2 mRNA vaccine dose in a supervised setting equipped to manage severe allergic reactions can be safe.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Golden reported receiving grants from Pfizer, GSK, Novartis, Genentech, and Regeneron outside the submitted work. Dr Blumenthal reported receiving grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, Agency for Healthcare Research and Quality (AHRQ), Massachusetts General Hospital Executive Committe on Research, Department of Medicine (DOM) Transformative Scholar Award, and DOM COVID-19 Junior Investigator Initiative; personal fees from Weekley, Schulte, Valdes, Murman, Tonelli, Piedmont Liability Trust, and Vasios, Kelly & Strollo PA; and royalties from UpToDate Inc outside the submitted work. Dr Stone reported receiving grants from the AHRQ and American Academy of Allergy, Asthma & Immunology Foundation Career Development Award during the conduct of the study. Dr Shaker reported being a member of the Joint Taskforce on Allergy Practice Parameters; having a family member who is CEO of Altrix Medical; being an associate editor for the Annals of Allergy, Asthma & Immunology; and serving on the editorial boards of the Journal of Allergy and Clinical Immunology In Practice and the Journal of Food Allergy. Dr Greenhawt reported serving as a consultant for Aquestive; being a member of physician/medical advisory boards for DBV Technologies, Sanofi/Regeneron, Genentech, Nutricia, Novartis, Acquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Pfizer, US World Meds, Allergenis, Aravax, and Prota, all unrelated to vaccines/vaccine development or COVID-19 treatment; being an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; being a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; being the senior associate editor for the Annals of Allergy, Asthma & Immunology; being a member of the Joint Taskforce on Allergy Practice Parameters; receiving honoraria for lectures from ImSci, MedLearningGroup, and multiple state/local allergy societies; and receiving past research support ending in 2020 from the AHRQ (K08-HS024599). No other disclosures were reported.

Figures

Figure 1.
Figure 1.. PRISMA Diagram for Study Selection
Figure 2.
Figure 2.. Pooled Incidence of Immediate Severe Allergic Reactions to a Second SARS-CoV-2 mRNA Dose Among Persons Who Had an Immediate Allergic Reaction to Their First SARS-CoV-2 mRNA Vaccine Dose
aFor analysis purposes, this study by Krantz et al was combined with the 3 cases (all anaphylaxis) from Wolfson et al given that these 2 studies had overlap of cases.
See this image and copyright information in PMC

References

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