In December 2020, the FDA granted emergency use authorization for mRNA COVID-19 vaccines from Pfizer-BioNTech and Moderna. However, within days of this authorization, there were several reports of severe allergic reactions to the vaccines. This led to widespread concern about the safety of these vaccines, creating a barrier to mass vaccination efforts. “There has been much concern regarding vaccine safety from an allergy standpoint,” says Lily Li, MD.

According to Kimberly G. Blumenthal, MD, MSc, many people who report COVID-19 vaccine-related reactions have a history of prior allergic reactions. “However, the specific risk factors for allergy symptoms after COVID-19 vaccination are not well known,” she says. “It’s important to understand who may be at highest risk.”

Risk Factors for Allergic Symptoms Assessed Post-Vaccination

For a study published in JAMA Network Open, Dr. Li, Dr. Blumenthal, and colleagues evaluated the association between self-reported high-risk allergy history and allergy symptoms after mRNA COVID-19 vaccination. “The goal of our study was to assess risk factors for allergic symptoms following mRNA COVID-19 vaccination so we can better understand the overall safety of these vaccines and help guide safe vaccination practices for those at highest risk,” says Dr. Li.

The study involved nearly 60,000 healthcare employees who received at least one dose of an mRNA COVID-19 vaccine between December 14, 2020, and February 1, 2021. Participants also needed to complete at least one post-vaccination symptom survey in the 3 days after vaccination. Less than 1% of the study cohort reported a history of high-risk allergy.

High-Risk Allergy History Correlates With More Allergic Reactions

“Our study found that while individuals with a high-risk allergy history reported more allergic symptoms in the 3 days following mRNA COVID-19 vaccine, nearly everyone—regardless of allergy history—safely completed the two-dose vaccine series,” says Dr. Blumenthal. “Risks for an allergic reaction were higher after the first dose, but most participants reported symptoms did not hinder completion of the second dose. An increased risk of reporting allergic symptoms was seen in female and Black persons and those vaccinated with the Moderna vaccine.”

Individuals who reported a high-risk allergy history had a 2.5-fold higher risk for allergy symptoms after mRNA vaccination than those without such a history (11.6% vs 4.7%) during the 3 days after vaccination (Table). “For those reporting a high-risk allergy, the highest risk was seen was for hives/urticaria (relative risk [RR], 3.81) and for swelling/angioedema (RR, 4.36),” Dr. Li says. “It should be noted that severe allergic reactions to an mRNA vaccine were rare.”

Most Reported Allergic Symptoms Were Mild

According to Dr. Li, the study findings support the overall safety of mRNA vaccine in all eligible individuals, regardless of high-risk allergy history. “Symptoms such as hives and swelling may occur, but most reported allergic-type symptoms were mild and did not hinder completion of the vaccine series,” she says.

Dr. Blumenthal adds that the findings contribute to the growing body of evidence regarding safety of mRNA vaccination in patients with a high-risk allergy history. “We hope these data will help inform discussions with patients, particularly with those who are hesitant to receive mRNA COVID-19 vaccine due to allergic concerns,” she says.

The researchers concur that future studies are needed to better understand risk factors for allergic reactions after receipt of an mRNA COVID-19 vaccine. “Interestingly, recent data indicate that even for individuals who report an immediate and potentially allergic reaction after a first dose of an mRNA COVID-19 vaccine, a second dose can be safely administered,” Dr. Li says. “This suggests that many vaccine-related reactions may not be truly allergic or occur through non-IgE mediated mechanisms. These factors warrant further investigation.”

It is also critical to better understand the impact of perceived allergy symptoms on vaccine hesitancy. “Considering the overall safety data presented in our study, more work directed at better understanding reasons for delaying or not completing COVID-19 vaccination is needed,” Dr. Blumenthal says. “Such data can inform strategies to target vaccine hesitancy associated with allergic concerns.”