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.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed 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 World Health Organizstion (WHO) global coronavirus database, and the gray 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 Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although 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.

Greenhawt M ，Abrams EM ，Shaker M ，Chu DK ，Khan D ，Akin C ，Alqurashi W ，Arkwright P ，Baldwin JL ，Ben-Shoshan M ，Bernstein J ，Bingemann T ，Blumchen K ，Byrne A ，Bognanni A ，Campbell D ，Campbell R ，Chagla Z ，Chan ES ，Chan J ，Comberiati P ，Dribin TE ，Ellis AK ，Fleischer DM ，Fox A ，Frischmeyer-Guerrerio PA ，Gagnon R ，Grayson MH ，Horner CC ，Hourihane J ，Katelaris CH ，Kim H ，Kelso JM ，Lang D ，Ledford D ，Levin M ，Lieberman J ，Loh R ，Mack D ，Mazer B ，Mosnaim G ，Munblit D ，Mustafa SS ，Nanda A ，Oppenheimer J ，Perrett KP ，Ramsey A ，Rank M ，Robertson K ，Sheikh J ，Spergel JM ，Stukus D ，Tang MLK ，Tracy JM ，Turner PJ ，Whalen-Browne A ，Wallace D ，Wang J ，Waserman S ，Witry JK ，Worm M ，Vander Leek TK ，Golden DBK ... -  《-》

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

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.

Greenhawt M ，Dribin TE ，Abrams EM ，Shaker M ，Chu DK ，Golden DBK ，Akin C ，Anagnostou A ，ALMuhizi F ，Alqurashi W ，Arkwright P ，Baldwin JL ，Banerji A ，Bégin P ，Ben-Shoshan M ，Bernstein J ，Bingemann TA ，Bindslev-Jensen C ，Blumenthal K ，Byrne A ，Cahill J ，Cameron S ，Campbell D ，Campbell R ，Cavender M ，Chan ES ，Chinthrajah S ，Comberiati P ，Eastman JJ ，Ellis AK ，Fleischer DM ，Fox A ，Frischmeyer-Guerrerio PA ，Gagnon R ，Garvey LH ，Grayson MH ，Isabwe GAC ，Hartog N ，Hendron D ，Horner CC ，Hourihane JO ，Iglesia E ，Kan M ，Kaplan B ，Katelaris CH ，Kim H ，Kelso JM ，Khan DA ，Lang D ，Ledford D ，Levin M ，Lieberman JA ，Loh R ，Mack DP ，Mazer B ，Mody K ，Mosnaim G ，Munblit D ，Mustafa SS ，Nanda A ，Nathan R ，Oppenheimer J ，Otani IM ，Park M ，Pawankar R ，Perrett KP ，Peter J ，Phillips EJ ，Picard M ，Pitlick M ，Ramsey A ，Rasmussen TH ，Rathkopf MM ，Reddy H ，Robertson K ，Rodriguez Del Rio P ，Sample S ，Sheshadri A ，Sheik J ，Sindher SB ，Spergel JM ，Stone CA ，Stukus D ，Tang MLK ，Tracy JM ，Turner PJ ，Vander Leek TK ，Wallace DV ，Wang J ，Wasserman S ，Weldon D ，Wolfson AR ，Worm M ，Yacoub MR ... -  《-》

Risk of Second Allergic Reaction to SARS-CoV-2 Vaccines: A Systematic Review and Meta-analysis.

Chu DK ，Abrams EM ，Golden DBK ，Blumenthal KG ，Wolfson AR ，Stone CA Jr ，Krantz MS ，Shaker M ，Greenhawt M ... -  《-》

First-Dose mRNA COVID-19 Vaccine Allergic Reactions: Limited Role for Excipient Skin Testing.

The Centers for Disease Control and Prevention state that a severe or immediate allergic reaction to the first dose of an mRNA COVID-19 vaccine is a contraindication for the second dose. To assess outcomes associated with excipient skin testing after a reported allergic reaction to the first dose of mRNA COVID-19 vaccine. We identified a consecutive sample of patients with reported allergic reactions after the first dose of mRNA COVID-19 vaccine who underwent allergy assessment with skin testing to polyethylene glycol (PEG) and, when appropriate, polysorbate 80. Skin testing results in conjunction with clinical phenotyping of the first-dose mRNA COVID-19 vaccine reaction guided second-dose vaccination recommendation. Second-dose mRNA COVID-19 vaccine reactions were assessed. Eighty patients with reported first-dose mRNA COVID-19 vaccine allergic reactions (n = 65; 81% immediate onset) underwent excipient skin testing. Of those, 14 (18%) had positive skin tests to PEG (n = 5) and/or polysorbate 80 (n = 12). Skin testing result did not affect tolerance of the second dose in patients with immediate or delayed reactions. Of the 70 patients who received the second mRNA COVID-19 vaccine dose (88%), 62 had either no reaction or a mild reaction managed with antihistamines (89%), but 2 patients required epinephrine treatment. Three patients with positive PEG-3350 intradermal (methylprednisolone) testing tolerated second-dose mRNA COVID-19 vaccination. Refresh Tears caused nonspecific skin irritation. Most individuals with a reported allergic reaction to the first dose of mRNA COVID-19 vaccines, regardless of skin test result, received the second dose safely. More data are needed on the value of skin prick testing to PEG (MiraLAX) in evaluating patients with mRNA COVID-19 vaccine anaphylaxis. Refresh Tears should not be used for skin testing.

Wolfson AR ，Robinson LB ，Li L ，McMahon AE ，Cogan AS ，Fu X ，Wickner P ，Samarakoon U ，Saff RR ，Blumenthal KG ，Banerji A ... -  《-》

Evaluation of pediatric patients with suspected polyethylene glycol and polysorbate allergy before mRNA SARS-CoV2 vaccination.

Karaaslan BG ，Burtecene N ，Mustu U ，Ocak S ，Kasapcopur O ，Kıykım A ，Cokugras H ... -  《-》