The risk of immediate allergic reactions or anaphylaxis after a second dose of the SARS-CoV-2 mRNA vaccine is low in individuals who had an allergic reaction to their first dose of the vaccine, according to a systematic review and meta-analysis published in JAMA Internal Medicine.

The findings suggest revaccination of people who had an immediate allergic reaction to a first dose of the vaccine (less than 4 hours after the shot) can be safe if administered in a supervised setting equipped to manage severe reactions. However, the review also showed 1 in 7 patients may have experienced mild symptoms.

Databases including MEDLINE, Embase, Web of Science, and the World Health Organization Global Coronavirus Database were perused for studies of any design from inception through October 4, 2021. The search looked for studies on the risk of a second allergic reaction of any severity to the mRNA vaccination in people who had a previous reaction to the vaccine. The researchers excluded studies describing delayed reactions occurring more than 4 hours after vaccination as well as those not discussing patients with prior allergic reactions.

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From 22 case studies or reports, 1366 individuals (87.8% women; mean age, 46.1 years) had immediate allergic reactions to their first inoculation. Utilizing the pooled random-effects model, the researchers observed that 6 patients developed severe immediate allergic reactions after the second vaccination (absolute risk, 0.16%; 95% CI, 0.01%-2.94%), and 232 had mild symptoms (13.65%; 95% CI, 7.76%-22.9%). Conversely, 1360 patients tolerated the dose (99.84%; 95% CI, 97.09%-99.99%). Of 78 people with severe immediate reactions to their first vaccination, 4 (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%). No deaths occurred.

Graded vaccine dosing, skin testing, and premedication used as risk-stratification strategies did not change the results. The evidence in this review and meta-analysis was considered moderate in certainty.

Limitations of the study were the small study numbers and a risk of selection bias in some of the component studies. This analysis also did not look at third doses of the vaccine.

“These findings contradict the common assumption that a history of immediate reaction, including severe immediate allergic reactions, to a prior SARS-CoV-2 mRNA vaccine guarantees another reaction after revaccination,” the authors noted. “These data should prompt reconsideration of a history of allergic reaction to a prior dose of SARS-CoV-2 mRNA vaccine as a contraindication to a second dose of the vaccine,” they advise.

Disclosure: Multiple authors declared affiliations with pharmaceutical and biopharmaceutical companies. Please refer to the original article for a full list of disclosures.


Chu DK, Abrams EM, Golden DBK, et al. Risk of second allergic reaction to SARS-CoV-2 vaccines: a systematic review and meta-analysis. JAMA Intern Med. Published online February 21, 2022. doi:10.1001/jamainternmed.2021.8515

This article originally appeared on Pulmonology Advisor