Abstract
This guidance updates 2021 GRADE recomendations regarding immediate allergic reactions following COVID-19 vaccines and addresses re-vaccinating individuals with 1st dose allergic reactions and allergy testing to determine re-vaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 re-vaccination 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 recommenations. 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 UK, and the US formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy, and re-vaccination after a prior immediate allergic reaction. We suggest against >15-minute post-vaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest re-vaccination 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 pre-medication, split-dosing, or special precautions because of a comorbid allergic history.
Key words: SARS-CoV-2, COVID-19, vaccination, adenovirus vector vaccine, mRNA COVID-19 vaccine, anaphylaxis, allergic reactions, repeat allergic reactions, polyethylene glycol, polysorbate 80, skin testing, shared decision-making, GRADE, allergy, allergy specialist
Footnotes
32 Allergy Clinic, Department of Dermatology and Allergy, Herlev and Gentofte Hospital and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Abbreviations: Coronavirus disease 2019(COVID-19), Vaccine Adverse Event Reaction System (VAERS), vaccine safety datalink (VSD) skin testing (ST), Grading of Recommendations Assessment, Development and Evaluation (GRADE), Research Electronic Data Capture (REDcap), National Institutes of Allergy and Infectious Diseases (NIAID), polyethylene glycol (PEG), polysorbate 80 (PS), Complement Activation-Related Pseudoallergy (CARPA), Immunization Stress-Related Response(ISRR), Canadian Society of Allergy and Clinical Immunology (CSACI), Credibility Interval (CrI), Confidence Interval (CI)
Funding: none
Trial Registration: not applicable
Conflicts of Interest
Matthew Greenhawt: has received past research support to his institution from DBV Technologies, and the Agency for Healthcare Research and Quality; receives current research support from Novartis and Silota; is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology, and is member of the Joint Taskforce on Allergy Practice Parameters. He has received honorarium for lectures from ImSci, RMEI Medical Education, MedLearningGroup, and multiple state/local allergy societies.
Timothy Dribin: has received support from the National Institutes of Health, under Award Number 25 2KL2TR001426-05A1 and the National Center for Advancing Translational Sciences of the National Institutes 26 of Health, under Award Number 2UL1TR001425 - 05A1. The content is solely the responsibility of the 27 authors and does not necessarily represent the official views of the NIH
Elissa Abrams: is a collaborator with the Institute for Health Metrics and Evaluation. She is na employee of Public Health Agency of Canada (PHAC) but the views expressed are her own and not that of PHAC.
Marcus Shaker: serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice, is an associate editor of Annals of Allergy, Asthma, and Immunology, is a member of the Joint Task Force on Practice Parameters, and has participated in research that has received funding from DBV.
David Golden: Speakers bureau honoraria from Genentech, Kaleo; Clinical trial support from Genentech, Thermo Fisher, Novartis, Pfizer, GSK, and Regeneron, all unrelated to vaccine/vaccine development or COVID-19 treatment; Consulting fees from Aquestive, Novartis, ALK; Royalties from UpToDate (section editor).
Cem Akin: consulting fees from Blueprint Medicine, Cogent, and Novartis; research support from Blueprint Medicines and Cogent; and royalties from UpToDate. Ronna L. Campbell: consulting fees from Bryn and royalties from UpToDate.
Aikaterini Anagnostou reports institutional funding from Aimmune Therapeutics and FARE (Food Allergy Research and Education), personal fees from DBV Technologies, ALK, and FARE.
Moshe Ben-Shoshan: Consultant for Novartis
Jonathan A. Berstein: principal investigator, consultant, and speaker for Novartis, Genentech, AZ, Sanofi Regeneron, Takeda/Shire, CSL Behring, Pharming, Biocryst, and Merck; consultant for Kalvista, Ionis, Celldex, Allakos, Amgen, Biomarin, and Blueprint Medicine; principal investigator and speaker for GSK; speaker for Optinose; consultant for Ono, Astria, Incyte, Cycle, and Escient; and royalties from UptoDate, BMJ, Taylor Francis, and Elsevier.
Theresa Bingeman: Consultant- ALK, Speaker-Sanofi, PI- Novartis, Aimmune- advisory board
Kimberly Blumenthal: receives grant support from the NIH/NIAID (R01AI150295, 2UM1AI109565-08), Phadia Ab (Thermo Fisher Scientific), and the Massachusetts General Hospital; personal fees for legal case review from Weekley Shulte Valdes Murman Tonelli, Piedmont Liability Trust, Vasios Kelly and Strollo PA, and Publix Supermarkets; and royalties from UpToDate, outside the submitted work.
Dianne Campbell: DBV employee (0.8FTE). Honorarium for Advisory Boards; AllerGenis, Westmead Fertility Centre. Research Grants to Institution from Department of Health, Australia & National Health and Medical Council of Australia
Ronna Campbell: is an author for UpToDate (Waltham, MA, USA) and a consultant for Bryn Pharma (Raleigh, NC, USA)
Edmond Chan: has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK; and is on the Executive of the CSACI (Canadian Society of Allergy and Clinical Immunology)
Sharon Chinthrajah: receives grant support from the Consortium for Food Allergy Research (CoFAR), National Institute of Allergy and Infectious Disease (NIAID), Food Allergy Research & Education (FARE), Aimmune, DBV Technologies, Astellas, Novartis, Regeneron, and Astra Zeneca, and is an advisory board member for Alladapt Immunotherapeutics, Novartis, Sanofi, Allergenis, Intrommune Therapeutics, and Genentech. There are no conflicts of interest in this publication
Anne Ellis: advisory boards for ALK-Abello, AstraZeneca, Aralez, Bausch Health, LEO Pharma, Merck, Novartis, and Pfizer; speakers’ bureaus for ALK-Abello, AstraZeneca, Miravo, Medexus, and Mylan; research support (paid to institution) from ALK-Abello, Aralez, AstraZeneca, Bayer LLC, Medexus, Novartis, and Regeneron; independent consultant to Bayer LLC and Regeneron; and royalties from UpToDate.
David Fleischer: has received research support to his institution from Aimmune Therapeutics and DBV Technologies; is a member of the medical advisory board for the Food Allergy & Anaphylaxis Connection Team (FAACT), medical advisory council for the National Peanut Board, the Adverse Reactions to Food Committee (former chair 2017-2019) for the AAAAI, and Food Allergy Committee for the ACAAI; has received royalties from UpToDate; and is a consultant to Allergenis, Aquestive Therapeutics, Aravax, Danone, DBV Technologies, Genentech, Nasus Pharma, and Nurture Inc. (Happy Family Organics).
Remi Gagnon: Clinical trials sponsored by : Regeneron, Novartis, Sanofi, AstraZeneca, GSK, ALK
Mitchell Grayson: is THE Editor-in-Chief of the Annals of Allergy, Asthma & Immunology, has served on advisory boards for AbbVie, GSK, and Merck, has stock options in Invirsa, Inc., serves of the Board of Directors of the Asthma and Allergy Foundation of America (AAFA), where he is Chair of their Medical Scientific Council, and is a member of the American Lung Association Scientific Advisory Committee
Nicholas Hartog: Horizon (speaker and ad board), Pharming (speaker, ad board, scientific steering committee), Chiesi (consultant), Takeda (ad board and speaker).
Johnathan Hourihane: Research funding: DBV Technologies; Aimmune Therapeutics, Johnson and Johnson, Temple St Foundation and Dublin Skin and Cancer Hospital Charity, Clemens von Pirquet Foundation.Consultancy: Aimmune Therapeutics, Johnson and Johnson
Harold Kim: Speakers’ bureau and/or advisory boards: ALK, AstraZeneca, Bausch Health, CSL Behring, GSK, Miravo, Novartis, Pediapharm, Pfizer, Sanofi, Shire, Takeda.
David Lang: honoraria, consultant, and/or clinical research support from AstraZeneca, Genentech, Novartis, and Sanofi-Regeneron; Guest Associate Editor of JACI:In Practice; and editorial board of DynaMed.
Denis Ledford: contributor to UpToDate for Perioperative Anaphylaxis; Contributing Editor for Ask the Expert (AAAAI); research support from AstraZeneca and Novartis (paid to institution); consultant for AstraZeneca; speaker bureau/honoraria from AstraZeneca, Genentech, GSK, and Sanofi/Regeneron; and legal opinion indoor fungal exposure, drug allergy, anaphylaxis.
Jay Lieberman: Research/Money to Institution: Aimmune, DBV, Regeneron Novartis. Consultant/Advisor: Aquestive, ALK, DBV, Novartis. Adjudication/DSMB: Abbvie, Siolta
Douglas Mack: has provided consultation and speaker services for Aimmune, Bausch Health, ALK-Abello, Medexus, Miravo and is an investigator for DBV and ALK-Abello and serves on the editorial board of the Journal of Food Allergy
Bruce Mazer: receives funding from the Canadian Institutes for Health Research, The National Science and Engineering Council for Canada and Candian Allergy Asthma and Immunology Foundation, and the McGill Univeristy Foundation
Gissele Mosnaim: received past research grant support from Teva, Astra-Zeneca, Alk-Abello, and Genentech and current research grant support from Sanofi-Regeneron, Novartis, and GlaxoSmithKline.
Shahzad Mustafa: Speakers bureau: Genentech, Regeneron/Sanofi, GSK, AstraZeneca, CSL Behring, Aimmune
John Oppenheimer: is a consultant for Amgen, Aimmune, Aquestive, GSK, Sanofi; member of the Adjudication or Data Safety Monitoring Board for Astra Zeneca, Amgen, Abbvie, Novartis, Glaxo Smith Kline; is the Executive Editor for the Annals of Allergy Asthma and Immunology; and a reviewer for UpToDate.
Kirsten Perrett: has received research grants from DBV Technologies, GSK, Novartis and Siolta Therapeutics and consultant fees from Aravax outside the submitted work, paid to her institution.
Matthieu Picard: Received lecture fees from Novartis
Allison Ramsey: Speaker’s Bureau GSK and Sanofi/Regeneron
Pablo Rodriguez del Rio: Research grant: Aimmune Therapeutics, FAES. Speaker for: GSK, FAES, Novartis, ALK-Abelló, LETI and Aimmune Therapeutics, Sanofi, Stallergenes. Advisory: FAES, Miravo
Ajay Sheshradi: Consultant, Enanta Pharmaceuticals
Sayatani Sindher: reports grants from NIH, Regeneron, DBV Technologies, Aimmune, Novartis, CoFAR, and FARE. She is an Advisory member at Genentech and DBV Technologies. There are no conflicts of interest in this publication.
Cosby Stone: receives research support from the AAAAI Foundation Faculty Development Award
David Stukus: Consultant – ARS Pharmaceuticals, Before Brands, Novartis, Parent MD; Research support – DBV Technologies; Honoraria – American Academy of Pediatrics, American College of Allergy, Asthma and Immunology; Member – Joint Task Force on Practice Parameters for Allergy/Immunology; Board of Regents for the American College of Allergy, Asthma and Immunology
Mimi Tang: declares consultant fees from Pfizer and Abbott Nutrition; was the past employee (ended July 2022) of and share interest/options in Prota Therapeutics; is the member of the Medical Advisory Board of Anaphylaxis & Anaphylaxis Australia; is the member of the Board of Directors of Asia Pacific Association of Allergy Asthma and Clinical Immunology and was the past member of the Board of Directors of the WAO (ended 2019); is the member of expert committees of the American Academy of Allergy, Asthma & Immunology, Asia Pacific Association of Allergy Asthma and Clinical Immunology, Australasian Society of Clinical Immunology and Allergy, and the World Health Organization.
Paul Turner: has received grants from Medical Research Council andcNIHR/Imperial Biomedical Research Centre; personal fees and non-financial support from Allergenis, plus grants from UK Medical Research Council, grants and personal fees from UK Food Standards Agency, personal fees and non-financial support from Aimmune Therapeutics, grants from Jon Moulton Charity Trust, personal fees from Aquestive all outside the submitted work.
Timothy Vander Leek: has served on advisory boards for and received honoraria from Aralez/Miravo, Bausch Health, Covis Pharma, and Pfizer
Julie Wang: receives research support from National Institute of Allergy and Infectious Diseases, Aimmune, DBV Technologies, and Regeneron, and consultancy fees from ALK Abello and Jubilant HollisterStier.
Susan Wasserman: consulting fees from GSK, Novartis, CSL Behring, Pfizer Canada, Sanofi Canada, AZ, Takeda, ALK Abello, Teva, Medexus, MiravoHealth, Mylan, Bausch Lomb, AbbVie, Avir Pharma, and Leo Pharma; research funding from Pfizer Canada, ALK-Abello, Aimmune; and president of Canadian Allergy, Asthma and Immunology Foundation.
Margitta Worm:
No conflicts to declare related to this work: Faisal ALMuhizi, Waleed Alquarshi, Peter Arkwright, James Baldwin, Aleena Banerji, Carsten Bindslev-Jensen, Aideen Byrne, Julia Cahil, Scott Cameron, Michael Cavander, Derek Chu, Pasquale Comberiatti, Jacquelin Eastman, Adam Fox, Pamela Frischmeyer-Gurrerio, Lene Garvey, David Hendron, Catherine Horner, Ghislaine Isabwe, Manstein Kan, Blanca Kaplan, Constance Katelaris, John Kelso, David Khan, Michael Levin, Richard Loh, Ketan Mody, Daniel Munblit, Richard Nathan, Anil Nanda, Miguel Park, Ruby Pawankar, Mitchell Pitlick, Elizabeth Phillips, Hari Reddy, Trine Rassumssen, Kara Robertson, Javed Shiek, Jonathan Spergel, James Tracey, Dana Wallace, David Weldon, Anna Wolfson, Mona-Rita Yacoub