Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach

Matthew Greenhawt; Timothy E Dribin; Elissa M Abrams; Marcus Shaker; Derek K Chu; David B K Golden; Cem Akin; Akterini Anagnostou; Faisal ALMuhizi; Waleed Alqurashi; Peter Arkwright; James L Baldwin; Aleena Banerji; Philippe Bégin; Moshe Ben-Shoshan; Jonathan Bernstein; Theresa A Bingemann; Carsten Bindslev-Jensen; Kim Blumenthal; Aideen Byrne; Julia Cahill; Scott Cameron; Dianne Campbell; Ronna Campbell; Michael Cavender; Edmond S Chan; Sharon Chinthrajah; Pasquale Comberiati; Jacqueline J Eastman; Anne K Ellis; David M Fleischer; Adam Fox; Pamela A Frischmeyer-Guerrerio; Remi Gagnon; Lene H Garvey; Mitchell H Grayson; Ghislaine Annie Clarisse Isabwe; Nicholas Hartog; David Hendron; Caroline C Horner; Johnathan O'B Hourihane; Edward Iglesia; Manstein Kan; Blanka Kaplan; Constance H Katelaris; Harold Kim; John M Kelso; David A Khan; David Lang; Dennis Ledford; Michael Levin; Jay A Lieberman; Richard Loh; Douglas P Mack; Bruce Mazer; Ketan Mody; Gisele Mosnaim; Daniel Munblit; S Shahzad Mustafa; Anil Nanda; Richard Nathan; John Oppenheimer; Iris M Otani; Miguel Park; Ruby Pawankar; Kirsten P Perrett; Jonny Peter; Elizabeth J Phillips; Matthieu Picard; Mitchell Pitlick; Allison Ramsey; Trine Holm Rasmussen; Melinda M Rathkopf; Hari Reddy; Kara Robertson; Pablo Rodriguez Del Rio; Stephen Sample; Ajay Sheshadri; Javed Sheik; Sayantani B Sindher; Jonathan M Spergel; Cosby A Stone; David Stukus; Mimi L K Tang; James M Tracy; Paul J Turner; Timothy K Vander Leek; Dana V Wallace; Julie Wang; Susan Wasserman; David Weldon; Anna R Wolfson; Margitta Worm; Mona-Rita Yacoub

doi:10.1016/j.jaci.2023.05.019

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach

J Allergy Clin Immunol. 2023 Aug;152(2):309-325. doi: 10.1016/j.jaci.2023.05.019. Epub 2023 Jun 7.

Authors

Matthew Greenhawt¹, Timothy E Dribin², Elissa M Abrams³, Marcus Shaker⁴, Derek K Chu⁵, David B K Golden⁶, Cem Akin⁷, Akterini Anagnostou⁸, Faisal ALMuhizi⁹, Waleed Alqurashi¹⁰, Peter Arkwright¹¹, James L Baldwin⁷, Aleena Banerji¹², Philippe Bégin¹³, Moshe Ben-Shoshan¹⁴, Jonathan Bernstein¹⁵, Theresa A Bingemann¹⁶, Carsten Bindslev-Jensen¹⁷, Kim Blumenthal¹², Aideen Byrne¹⁸, Julia Cahill¹⁹, Scott Cameron²⁰, Dianne Campbell²¹, Ronna Campbell²², Michael Cavender²³, Edmond S Chan²⁴, Sharon Chinthrajah²⁵, Pasquale Comberiati²⁶, Jacqueline J Eastman²⁷, Anne K Ellis²⁸, David M Fleischer²⁹, Adam Fox³⁰, Pamela A Frischmeyer-Guerrerio³¹, Remi Gagnon³², Lene H Garvey³³, Mitchell H Grayson³⁴, Ghislaine Annie Clarisse Isabwe¹⁴, Nicholas Hartog²⁷, David Hendron³⁵, Caroline C Horner³⁶, Johnathan O'B Hourihane³⁷, Edward Iglesia³⁸, Manstein Kan³⁹, Blanka Kaplan⁴⁰, Constance H Katelaris⁴¹, Harold Kim⁴², John M Kelso⁴³, David A Khan⁴⁴, David Lang⁴⁵, Dennis Ledford⁴⁶, Michael Levin⁴⁷, Jay A Lieberman⁴⁸, Richard Loh⁴⁹, Douglas P Mack⁵⁰, Bruce Mazer¹⁴, Ketan Mody⁵¹, Gisele Mosnaim⁵², Daniel Munblit⁵³, S Shahzad Mustafa⁵⁴, Anil Nanda⁵⁵, Richard Nathan⁵⁶, John Oppenheimer⁵⁷, Iris M Otani⁵⁸, Miguel Park⁵⁹, Ruby Pawankar⁶⁰, Kirsten P Perrett⁶¹, Jonny Peter⁶², Elizabeth J Phillips⁶³, Matthieu Picard⁶⁴, Mitchell Pitlick⁵⁹, Allison Ramsey⁵⁴, Trine Holm Rasmussen¹⁷, Melinda M Rathkopf⁶⁵, Hari Reddy⁶⁶, Kara Robertson⁶⁷, Pablo Rodriguez Del Rio⁶⁸, Stephen Sample⁶⁹, Ajay Sheshadri⁷⁰, Javed Sheik⁷¹, Sayantani B Sindher²⁵, Jonathan M Spergel⁷², Cosby A Stone³⁸, David Stukus³⁴, Mimi L K Tang⁷³, James M Tracy⁷⁴, Paul J Turner⁷⁵, Timothy K Vander Leek⁷⁶, Dana V Wallace⁷⁷, Julie Wang⁷⁸, Susan Wasserman⁷⁹, David Weldon⁸⁰, Anna R Wolfson¹², Margitta Worm⁸¹, Mona-Rita Yacoub⁸²

Affiliations

¹ Section of Allergy and Clinical Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colo. Electronic address: Matthew.Greenhawt@childrenscolorado.org.
² Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
³ Department of Pediatrics and Child Health, Section of Allergy and Immunology, The University of Manitoba, Winnipeg, Canada.
⁴ Dartmouth-Hitchcock Medical Center, Section of Allergy and Immunology, Lebanon, NH; Dartmouth Geisel School of Medicine, Hanover, NH.
⁵ Faculty of Medicine, and the Department of McMaster University, Hamilton, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada; The Research Institute of St. Joe's Hamilton, Hamilton, Canada; Evidence in Allergy Group, McMaster University Medical Centre, Hamilton, Canada.
⁶ Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Bethesda.
⁷ Division of Allergy and Clinical Immunology, Department of Internal Medicine, University of Michigan School, Ann Arbor, Mich.
⁸ Section of Immunology, Allergy, and Retrovirology, Department of Pediatrics, Baylor College of Medicine, Houston, Tex; Section of Immunology, Allergy and Retrovirology, Department of Pediatrics, Texas Children's Hospital, Houston, Tex.
⁹ Division of Allergy and Clinical Immunology, Department of Internal Medicine, Security Forces Hospital Program, Riyadh, Arabia.
¹⁰ Department of Pediatrics and Emergency Medicine, University of Ottawa, Ottawa, Canada.
¹¹ Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom.
¹² Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
¹³ Centre Hospital Universitaire Sainte-Justine, Montreal, Canada.
¹⁴ Division of Allergy, Immunology, and Dermatology, Department of Pediatrics, McGill University Health Center-Montreal Children's Hospital, Montreal, Canada.
¹⁵ Division of Immunology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio.
¹⁶ Division of Allergy, Immunology, and Rheumatology, University of Rochester School of Medicine and Dentistry, Rochester, NY.
¹⁷ Department of Dermatology and Allergy Center, Odense Research Centre for Anaphylaxis, Odense, Denmark.
¹⁸ Department of Paediatrics, School of Medicine, Trinity College Dublin, Dublin, Ireland.
¹⁹ University of Alberta, Faculty of Medicine, Calgary, Canada.
²⁰ Allergy Victoria, Victoria, British Columbia, Canada.
²¹ The Children's Hospital at Westmead, Sydney, Australia.
²² Department of Emergency Medicine, Mayo Clinic, Rochester.
²³ Carilion Clinic, Verona, Va.
²⁴ Division of Allergy and Immunology, BC Children's Hospital, The University of British Columbia, Vancouver, Canada.
²⁵ Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Stanford University School of Medicine, Palo Alto, Calif; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, Calif; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Palo Alto, Calif.
²⁶ Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, Pisa, Italy.
²⁷ Corewell Health Allergy and Immunology, Grand Rapids, Mich; Michigan State University College of Human Medicine, Grand Rapids, Mich.
²⁸ Division of Allergy and Immunology, Department of Medicine, Queen's University, Kingston, Canada.
²⁹ Section of Allergy and Clinical Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colo.
³⁰ Guys's and St Tomas's Hospital National Health Service Foundation Trust, London, Mass.
³¹ Laboratory of Allergic Diseases, Food Allergy Research Section, National Institutes of Allergy and Infectious Diseases, the National Institutes of Health, Bethesda, Md.
³² Clinique Spécialisée en Allergie de la Capitale, Québec, Canada.
³³ Allergy Clinic, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
³⁴ Division of Allergy and Immunology, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio.
³⁵ Access Health Care Physicians LLC, New Port Richey, Fla.
³⁶ Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, Mo.
³⁷ Department of Paediatrics, Royal College of Surgeons, Dublin, Ireland.
³⁸ Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
³⁹ Fraser Allergy, Langley, Canada.
⁴⁰ Division of Allergy and Immunology, Northwell Health, New York, NY.
⁴¹ Campbelltown Hospital, Western Sydney University, Sydney, Australia.
⁴² Faculty of Medicine, and the Department of McMaster University, Hamilton, Canada; Division of Clinical Immunology and Allergy, Department of Medicine, Western University, St Joseph's Health Care, London (Canada), Mass.
⁴³ Division of Allergy, Asthma, and Immunology, Scripps Clinic, San Diego, Calif.
⁴⁴ Division of Allergy and Immunology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Tex.
⁴⁵ Department of Allergy and Clinical Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
⁴⁶ Division of Allergy and Immunology, Department of Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla.
⁴⁷ Division of Paediatric Allergology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁴⁸ Division of Allergy and Immunology, The University of Tennessee, Memphis, Tenn.
⁴⁹ Immunology Department, Perth Children's Hospital, Perth, Australia.
⁵⁰ Department of Pediatrics, McMaster University, Hamilton, Canada; Halton Pediatric Allergy, Burlington, Canada.
⁵¹ Elite Sports Medicine Institute Ltd, Westmont, Ill.
⁵² Division of Pulmonary, Allergy and Critical Care, Department of Medicine, NorthShore University Health System, Evanston, Ill.
⁵³ Inflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, Mass.
⁵⁴ Rochester Regional Health, University of Rochester School of Medicine and Dentistry, Rochester, NY.
⁵⁵ Division of Allergy and Immunology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Tex; Asthma and Allergy Center, Lewisville and Flower Mound, Dallas, Tex.
⁵⁶ Idaho Falls Infectious Diseases, Idaho Falls, Idaho.
⁵⁷ University of Medicine and Dentistry of New Jersey, Rutgers University School of Medicine, New Brunswick, NJ.
⁵⁸ Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California San Francisco, San Francisco, Calif.
⁵⁹ Division of Allergic Diseases, Mayo Clinic, Rochester.
⁶⁰ Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
⁶¹ Division of Pulmonary, Allergy and Critical Care, Department of Medicine, NorthShore University Health System, Evanston, Ill; Population Allergy Group and the Centre for Food and Allergy Research, Murdoch Children's Research Institute, University of Melbourne, University of Melbourne, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
⁶² Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town and the Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town.
⁶³ Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
⁶⁴ Hôspital Maisonneuve-Rosemont, Université de Montréal, Montreal, Canada.
⁶⁵ Allergy and Asthma Associates of Allen, Allen, Tex.
⁶⁶ Allergy, Asthma and Immunology Center of Alaska, Anchorage, Alaska; Department of Pediatrics, University of Washington School of Medicine, Seattle, Wash.
⁶⁷ Division of Clinical Immunology and Allergy, St Joseph's Health Care, London (Canada), Mass; Schulich School of Medicine and Dentistry, Western University, St Joseph's Health Care, London (Canada), Mass.
⁶⁸ Allergy Department, University Hospital Niño Jesus, Madrid, Spain.
⁶⁹ Memorial Hospital and Health Care Center, Jasper, Ind.
⁷⁰ Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Tex.
⁷¹ Kaiser Permanente Los Angeles Medical Center, Los Angeles, Calif.
⁷² Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pa.
⁷³ Department of Allergy Immunology, Murdoch Children's Research Institute, Melbourne, Parkville, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
⁷⁴ Allergy, Asthma, and Immunology Associates PC, Omaha, Neb; Department of Pediatrics, University of Nebraska School of Medicine, Omaha, Neb.
⁷⁵ Imperial College Healthcare National Health Service Trust, London, Mass; Royal Brompton and Harefield National Health Service Foundation Trust, London, Mass.
⁷⁶ Pediatric Allergy and Immunology, Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Canada.
⁷⁷ Nova Southeastern University College of Allopathic Medicine, Fort Lauderdale, Fla.
⁷⁸ Division of Pediatric Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY; Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷⁹ Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Canada.
⁸⁰ Baylor Scott and White Clinic, College Station, Tex.
⁸¹ Division of Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁸² Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Hospital, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Segrate, Milan, Italy.

Abstract

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Keywords: COVID-19; SARS-CoV-2; allergic reactions; anaphylaxis; mRNA COVID-19 vaccine; polyethylene glycol; polysorbate 80; repeat allergic reactions; skin testing; vaccination.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Anaphylaxis*
COVID-19 Vaccines / adverse effects
COVID-19* / prevention & control
Consensus
Excipients
GRADE Approach
Humans
Hypersensitivity, Immediate*
Vaccine Excipients

Substances

COVID-19 Vaccines
Vaccine Excipients
Excipients

Abstract

Publication types

MeSH terms

Substances

Grants and funding