Study Finds Second COVID-19 Vaccine Dose is Safe Following Allergic Reaction to First Dose

Study suggests that immediate onset mRNA vaccine reactions may not be caused by classic allergy, or IgE-mediated hypersensitivity.

Among those who experienced an allergic reaction to the first dose of the messenger RNA (mRNA) COVID-19 vaccine, all individuals who received a second dose tolerated it well, according to researchers from Massachusetts General Hospital (MGH).

Reported allergic reactions to the first dose of mRNA vaccines have been as high as 2%, according to the research published in JAMA International Medicine. Anaphylaxis occurs in up to 2.5 out of every 10,000 vaccine recipients, although the investigators noted that reactions can present in various ways.

“These reactions could include symptoms such as itching or hives or flushing,” said co-lead author Matthew S. Krantz, MD, from Vanderbilt University Medical Center, in a press release. “The patients included [in the study] were all advised by allergy specialists after their dose one reaction.”

Of 189 patients included in the analysis, 32 (17%) experienced anaphylaxis following their first dose of the vaccine and 159 (84%) went on to receive a second dose. All of those patients, including 19 individuals who had experienced anaphylaxis after their first dose, tolerated the second dose. Specifically, 32 patients (20%) reported immediate and potentially allergic symptoms that were self-limited, mild, and resolved with antihistamines alone.

“One important point from this study is that these immediate onset mRNA vaccine reactions may not be mechanistically caused by classic allergy, called immediate hypersensitivity or IgE-mediated hypersensitivity,” said co-senior author Kimberly G. Blumenthal, MD, MSc, co-director of the Clinical Epidemiology Program in MGH’s Division of Rheumatology, Allergy, and Immunology, in the press release. “For classic allergy, re-exposure to the allergen causes the same or even worse symptoms.”

Importantly, these findings suggest that it is safe for most individuals to receive a second dose of the mRNA COVID-19 vaccine, according to the study authors.

“After first dose reactions, allergy specialists may be useful to help guide risk/benefit assessments and assist with completion of safe vaccination,” said Aleena Banerji, MD, clinical director of the Allergy and Clinical Immunology Unit at MGH, in the press release.


Second COVID-19 mRNA vaccine dose found safe following allergic reactions to first dose. News release. Massachusetts General Hospital; July 26, 2021. Accessed August 5, 2021.

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