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

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

doi:10.1016/j.jaip.2021.06.006

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

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

Research output: Contribution to journal › Review article › peer-review

158 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	3546-3567
Number of pages	22
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	9
Issue number	10
DOIs	https://doi.org/10.1016/j.jaip.2021.06.006
State	Published - Oct 2021

Keywords

Adenovirus-vector vaccine
Allergic reactions
Allergy
Allergy specialist
Anaphylaxis
COVID-19
GRADE
Polyethylene glycol
Polysorbate 80
SARS-CoV-2
Shared decision making
Skin testing
Vaccination
mRNA vaccine

ASJC Scopus subject areas

Immunology and Allergy

Access to Document

10.1016/j.jaip.2021.06.006

Cite this

Greenhawt, M., Abrams, E. M., Shaker, M., Chu, D. K., Khan, D., Akin, C., Alqurashi, W., Arkwright, P., Baldwin, J. L., Ben-Shoshan, M., Bernstein, J., Bingemann, T., Blumchen, K., Byrne, A., Bognanni, A., Campbell, D., Campbell, R., Chagla, Z., Chan, E. S., ... Golden, D. B. K. (2021). 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. Journal of Allergy and Clinical Immunology: In Practice, 9(10), 3546-3567. https://doi.org/10.1016/j.jaip.2021.06.006

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 et al.
In: Journal of Allergy and Clinical Immunology: In Practice, Vol. 9, No. 10, 10.2021, p. 3546-3567.

Research output: Contribution to journal › Review article › peer-review

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 2021, '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', Journal of Allergy and Clinical Immunology: In Practice, vol. 9, no. 10, pp. 3546-3567. https://doi.org/10.1016/j.jaip.2021.06.006

@article{e2b476350fb74c1d9ede502c1acdb401,

title = "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",

abstract = "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.",

keywords = "Adenovirus-vector vaccine, Allergic reactions, Allergy, Allergy specialist, Anaphylaxis, COVID-19, GRADE, Polyethylene glycol, Polysorbate 80, SARS-CoV-2, Shared decision making, Skin testing, Vaccination, mRNA vaccine",

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

note = "Publisher Copyright: {\textcopyright} 2021 American Academy of Allergy, Asthma & Immunology",

year = "2021",

month = oct,

doi = "10.1016/j.jaip.2021.06.006",

language = "English (US)",

volume = "9",

pages = "3546--3567",

journal = "Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "Elsevier",

number = "10",

}

TY - JOUR

T1 - The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management

T2 - A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach

AU - Greenhawt, Matthew

AU - Abrams, Elissa M.

AU - Shaker, Marcus

AU - Chu, Derek K.

AU - Khan, David

AU - Akin, Cem

AU - Alqurashi, Waleed

AU - Arkwright, Peter

AU - Baldwin, James L.

AU - Ben-Shoshan, Moshe

AU - Bernstein, Jonathan

AU - Bingemann, Theresa

AU - Blumchen, Katharina

AU - Byrne, Aideen

AU - Bognanni, Antonio

AU - Campbell, Dianne

AU - Campbell, Ronna

AU - Chagla, Zain

AU - Chan, Edmond S.

AU - Chan, Jeffrey

AU - Comberiati, Pasquale

AU - Dribin, Timothy E.

AU - Ellis, Anne K.

AU - Fleischer, David M.

AU - Fox, Adam

AU - Frischmeyer-Guerrerio, Pamela A.

AU - Gagnon, Remi

AU - Grayson, Mitchell H.

AU - Horner, Caroline C.

AU - Hourihane, Jonathan

AU - Katelaris, Constance H.

AU - Kim, Harold

AU - Kelso, John M.

AU - Lang, David

AU - Ledford, Dennis

AU - Levin, Michael

AU - Lieberman, Jay

AU - Loh, Richard

AU - Mack, Doug

AU - Mazer, Bruce

AU - Mosnaim, Giselle

AU - Munblit, Daniel

AU - Mustafa, S. Shahzad

AU - Nanda, Anil

AU - Oppenheimer, John

AU - Perrett, Kirsten P.

AU - Ramsey, Allison

AU - Rank, Matthew

AU - Robertson, Kara

AU - Sheikh, Javed

AU - Spergel, Jonathan M.

AU - Stukus, David

AU - Tang, Mimi L.K.

AU - Tracy, James M.

AU - Turner, Paul J.

AU - Whalen-Browne, Anna

AU - Wallace, Dana

AU - Wang, Julie

AU - Waserman, Susan

AU - Witry, John K.

AU - Worm, Margitta

AU - Vander Leek, Timothy K.

AU - Golden, David B.K.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

KW - Adenovirus-vector vaccine

KW - Allergic reactions

KW - Allergy

KW - Allergy specialist

KW - Anaphylaxis

KW - COVID-19

KW - GRADE

KW - Polyethylene glycol

KW - Polysorbate 80

KW - SARS-CoV-2

KW - Shared decision making

KW - Skin testing

KW - Vaccination

KW - mRNA vaccine

UR - http://www.scopus.com/inward/record.url?scp=85110535672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85110535672&partnerID=8YFLogxK

U2 - 10.1016/j.jaip.2021.06.006

DO - 10.1016/j.jaip.2021.06.006

M3 - Review article

C2 - 34153517

AN - SCOPUS:85110535672

SN - 2213-2198

VL - 9

SP - 3546

EP - 3567

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

IS - 10

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this