The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-analysis, GRADE Assessment, and International Consensus Approach

Greenhawt, Matthew; Abrams, Elissa M.; Shaker, Marcus; Chu, Derek K.; Kahn, David; Akin, Cem; Alqurashi, Waleed; Arkwright, Peter; Baldwin, James L.; Ben-Shoshan, Moshe; Bernstein, Jonathan; Bingeman, Theresa; Blumchen, Katerina; Byrne, Aideen; Bognanni, Antonio; Campbell, Dianne; Campbell, Ronna; Chagla, Zain; Chan, Edmond S.; Chan, Jeffrey; Comberiatti, Pasquale; Dribin, Timothy E.; Ellis, Anne K.; Fleischer, David M.; Fox, Adam; Frischmeyer-Guerrerio, Pamela A.; Gagnon, Remi; Grayson, Mitchell H.; Horner, Caroline C.; Hourihane, Johnathan; Katelaris, Constance H.; Kim, Harold; Kelso, John M.; Lang, David; Ledford, Dennis; Levin, Michael; Lieberman, Jay; Loh, Richard; Mack, Doug; Mazer, Bruce; Mosnaim, Gissele; Munblit, Daniel; Mustafa, S Shahzad; Nanda, Anil; Oppenheimer, John; Perrett, Kirsten P.; Ramsey, Allison; Rank, Matt; Robertson, Kara; Shiek, Javed; Spergel, Jonathan M.; Stukus, David; Tang, Mimi LK.; Tracy, James M.; Turner, Paul J.; Whalen-Browne, Anna; Wallace, Dana; Wang, Julie; Wasserman, Susan; Witty, John K.; Worm, Margitta; Vander Leek, Timothy K.; Golden, David BK.

Concerns for anaphylaxis may hamper SARS-CoV-2 immunization efforts. We convened a multi-disciplinary group of international experts in anaphylaxis comprised of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the WHO global coronavirus database, and the grey literature (inception-March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the GRADE approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases/million (n=41,000,000 vaccinations, 95%CI 4.02-15.59; 26 studies, moderate certainty), the prevalence of PEG allergy is 103 cases/million (95%CI 88-120; 2 studies, very low certainty), and the sensitivity for PEG skin testing is poor though specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.