published Aug. 31, 2021, in JAMA Network Open. Symptoms resolved in a few hours with medication, and no patients required hospitalization.
Risk for allergic reaction has been one of several obstacles in global vaccination efforts, the authors, led by Nancy Agmon-Levin, MD, of the Sheba Medical Center, Ramat Gan, Israel, wrote. Clinical trials for the Moderna and Pfizer-BioNTech COVID-19 vaccines excluded individuals with allergies to any component of the vaccine or with previous allergies to other vaccines. Early reports of anaphylaxis in reaction to the vaccines caused concern among patients and practitioners. Soon after, the Centers for Disease Control and Prevention and other authorities released guidance on preparing for allergic reactions. “Despite these recommendations, uncertainty remains, particularly among patients with a history of anaphylaxis and/or multiple allergies,” the authors added.
In response to early concerns, the Sheba Medical Center opened a COVID-19 referral center to address safety questions and to conduct assessments of allergy risk for the Pfizer-BioNTech vaccine, the first COVID-19 vaccine approved in Israel. From Dec. 27, 2020, to Feb. 22, 2021, the referral center assessed 8,102 patients with allergies. Those who were not clearly at low risk filled out a questionnaire about prior allergic or anaphylactic reactions to drugs or vaccines, other allergies, and other relevant medical history. Patients were considered to be at high risk for allergic reactions if they met at least one of the following criteria: previous anaphylactic reaction to any drug or vaccine, multiple drug allergies, multiple other allergies, and mast cell disorders. Individuals were also classified as high risk if their health care practitioner deferred vaccination because of allergy concerns.
Nearly 95% of the cohort (7,668 individuals) were classified as low risk and received both Pfizer vaccine doses at standard immunization sites and underwent 30 minutes of observation after immunization. Although the study did not follow these lower-risk patients, “no serious allergic reactions were reported back to our referral center by patients or their general practitioner after immunization in the regular settings,” the authors wrote.
Five patients were considered ineligible for immunization because of known sensitivity to polyethylene glycol or multiple anaphylactic reactions to different injectable drugs, following recommendations from the Ministry of Health of Israel at the time. The remaining 429 individuals were deemed high risk and underwent observation for 2 hours from a dedicated allergy team after immunization. For these high-risk patients, both vaccine doses were administered in the same setting. Patients also reported any adverse reactions in the 21 days between the first and second dose.
Women made up most of the high-risk cohort (70.9%). The average age of participants was 52 years. Of the high-risk individuals, 63.2% reported prior anaphylaxis, 32.9% had multiple drug allergies, and 30.3% had multiple other allergies.
During the first 2 hours following immunization, nine individuals (2.1%), all women, experienced allergic reactions. Six individuals (1.4%) experienced minor reactions, including skin flushing, tongue or uvula swelling, or a cough that resolved with antihistamine treatment during the observation period. Three patients (0.7%) had anaphylactic reactions that occurred 10 to 20 minutes after injection. All three patients experienced significant bronchospasm, skin eruption, itching, and shortness of breath. Two patients experienced angioedema, and one patient had gastrointestinal symptoms. They were treated with adrenaline, antihistamines, and an inhaled bronchodilator. All symptoms resolved within 2-6 hours, and no patient required hospitalization.
In the days following vaccination, patients commonly reported pain at the injection site, fatigue, muscle pain, and headache; 14.7% of patients reported skin eruption, itching, or urticaria.
As of Feb. 22, 2021, 218 patients from this highly allergic cohort received their second dose of the vaccine. Four patients (1.8%) had mild allergic reactions. All four developed flushing, and one patient also developed a cough that resolved with antihistamine treatment. Three of these patients had experienced mild allergic reactions to the first dose and were premedicated for the second dose. One patient only reacted to the second dose.
The findings should be “very reassuring” to individuals hesitant to receive the vaccine, Elizabeth Phillips, MD, the director of the Center for Drug Safety and Immunology at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. She was not involved with the research and wrote an invited commentary on the study. “The rates of anaphylaxis and allergic reactions are truly quite low,” she said. Although about 2% of the high-risk group developed allergic reactions to immunization, the overall percentage for the entire cohort would be much lower.
The study did not investigate specific risk factors for and mechanisms of allergic reactions to COVID-19 vaccines, Dr. Phillips said, which is a study limitation that the authors also acknowledge. The National Institute for Allergy and Infectious Diseases is currently trying to answer some of these questions with a multisite, randomized, double-blinded study. The study is intended to help understand why people have these allergic reactions, Dr. Phillips added. Vanderbilt is one of the sites for the study.
While researchers continue to hunt for answers, the algorithm developed by the authors provides “a great strategy to get people that are at higher risk vaccinated in a monitored setting,” she said. The results show that “people should not be avoiding vaccination because of a history of anaphylaxis.”
Dr. Phillips has received institutional grants from the National Institutes of Health and the National Health and Medical Research Council; royalties from UpToDate and Lexicomp; and consulting fees from Janssen, Vertex, Biocryst, and Regeneron.
A version of this article first appeared on Medscape.com.