COVID-19 vaccine and anaphylaxis
Coronavirus disease 2019 (COVID-19), caused by the novel human-pathogenic coronavirus SARS-CoV-2, has affected over 108 million individuals with over 2.4 million deaths as of February 15, 2021.1 In December, vaccines from both Pfizer/BioNTech and Moderna were approved by Health Canada for individuals 16 and 18 years of age and older (respectively), providing the first glimmer of hope in viral prevention and mitigation.2 Both vaccines were studied in randomized, multinational, placebo-controlled observer-blinded efficacy trials, demonstrating very high efficacy with no significant difference in rates of adverse events including hypersensitivity events between the active and placebo arms of the studies.3,4 A study exclusion criteria for both trials was a history of a severe adverse reaction associated with the vaccine or component thereof (Pfizer also excluded anyone with a prior systemic reaction to any vaccine), though it should be noted that those with a history of allergies and anaphylaxis to unrelated substances (foods, insect venom, other medications) were not excluded from the study.3,4
On the first day of the Pfizer/BioNTech vaccine administration in the United Kingdom (UK), there were two reports of individuals experiencing anaphylaxis and another of a possible milder allergic reaction after receiving the vaccine, with both of the more severe reactions occurring in individuals who reported a history of severe allergic reactions.5 There have subsequently been reports of reactions consistent with anaphylaxis to both the Moderna and Pfizer/BioNTech vaccines - From December 14, 2020 to January 18, 2021 in the United States the Centers for Disease Control and Prevention (CDC) have reported 66 reports meeting criteria for anaphylaxis among vaccine recipients; 47 to the Pfizer-BioNTech vaccine (4.7 cases/million doses administered) and 19 to the Moderna vaccine (2.5 cases/million doses administered).6 All of these individuals have since recovered; there have been no reports of vaccine-associated anaphylaxis fatality due to the COVID-19 vaccines.7
The nature and cause of these reactions, including whether they were immunoglobulin E (IgE) mediated reactions, is still under investigation. Polyethylene glycol (PEG) has been identified as a possible allergen in both the Pfizer/BioNTech and Moderna vaccines, as adverse reactions to PEG have previously been reported in the literature and presumed to be IgE-mediated.8,9 Anti-PEG-IgE has been identified in previous investigations, unrelated to these vaccines, and testing protocols published.7 In addition, reports are emerging that PEG can generate complement activation products, suggesting a possible non-immune-mediated mechanism for adverse reactions to these compounds, including a proposed possible mechanism for adverse reactions to these vaccines.13 However, PEG is found in a multitude of commercial and medical products that are used and tolerated on a daily basis by Canadians, including laxatives, cosmetics, and food products.10 Reports of adverse reactions to PEG have historically been rare and largely limited to case reports.11,12 No cases of anaphylaxis have been reported in the literature to date due to PEG in any food product.
Canada’s National Advisory Committee on Immunization (NACI) has advised that the vaccine is contraindicated in individuals with a history of anaphylaxis to the COVID-19 vaccine or to any of its components.14 In individuals with a less severe allergy to the COVID-19 vaccine or to PEG, the NACI advises consultation with an allergist. Assessment by an allergist for those with a suspected allergy to a COVID-19 vaccine or one of its components is also highly recommended in a statement by the Canadian Society of Allergy and Clinical Immunology (CSACI), as evaluation allows the possibility of safe vaccine administration in a controlled environment using a graded administration/desensitization protocol, confirmation of allergy to one of the vaccine components if possible, or selection of a suitable alternative vaccine if necessary.15 The CSACI also affirms that other allergic conditions such as allergies to drugs, foods, insect venom or environmental allergens are not a contraindication to the COVID-19 vaccine, irrespective of severity.15
It is essential to understand that within the context of the persistent threat that COVID-19 poses to the health of Canadians, the risk of an allergic reaction to a vaccine is small. There is a theoretical risk of anaphylaxis with any vaccine. However, this risk has been rare. The estimated annual rate of anaphylaxis in Canada is approximately 0.4 to 1.8 cases per 1,000,000 doses of vaccine administration.16
Vaccine hesitancy will be essential to address if we hope to achieve success in fighting this pandemic, and accurate information about reactions as well as vaccine contraindications will be necessary for all clinicians. Clinicians will have an essential role in contextualizing this low risk of a reaction against the ongoing and real risk of COVID-19 for families and narrowing any divide between perceived and actual risk.17 Ensuring that information is presented expediently, credibly, and in understandable language will be essential for Canadians.17 An understanding that other allergic conditions – such as food allergy, stinging insect allergy, asthma, eczema and rhinitis – are neither contraindications nor precautions to receiving the vaccine and do not necessitate prolonged observation following vaccine administration, will be an essential part of the message as well. Unless one has a prior history of allergy to a vaccine component, which is thought to be exceptionally rare, this vaccine can – and should – be given to Canadians to mitigate the devastating impact of COVID-19.
Elissa M Abrams, Department of Pediatrics, Section of Allergy and Clinical Immunology,
University of Manitoba
Department of Pediatrics, Division of Allergy and Immunology, University of British
Columbia
Timothy K Vander Leek, Department of Pediatrics, University of Alberta
Competing Interests: EMA is a contributor to the Global Burden of Disease Unit at the Institute for Health Metrics and Evaluation in Seattle, is on the HealthCare Advisory Board of Food Allergy Canada, and has received moderator/speaker fees from Novartis, Sanofi and GSK. TVL has served on advisory boards and received honoraria from Aralez, Bausch Health, and Pfizer.
References
1. Johns Hopkins Coronavirus Resource Center [Internet]. Available from: https://coronavirus.jhu.edu/map.html
2. Health Canada: Pfizer-BioNTech COVID-19 vaccine: Authorization information [Internet]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/pfizer-biontech/authorization.html
3. Pfizer B. In: Vaccines and Related Biological Products Advisory Committee Meeting December 10, 2020. FDA, editor. 2020. https://www.fda.gov/media/144245/download.
4. Health Canada authorizes Moderna COVID-19 vaccine [Internet]. Available from: https://www.canada.ca/en/health-canada/news/2020/12/health-canada-authorizes-moderna-covid-19-vaccine.html
5. CNN: Third Alaskan health care worker has allergic reaction to Covid-19 vaccine [Internet]. Available from: https://www.cnn.com/2020/12/18/health/alaska-third-allergic-reaction-vaccine/index.html
6. Shimabukuro TT, Cole M, Su JR. Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 2020-January 18, 2021. JAMA [Internet]. 2021 Feb 12; Available from: https://doi.org/10.1001/jama.2021.1967
7. Banerji A, Wickner PG, Saff R, Stone C, Robinson L, Long A, et al. mRNA Vaccines to Prevent COVID-19 Disease and Reported Allergic Reactions: Current Evidence and Approach. J Allergy Clin Immunol Pr. 2020;in press.
8. Zhou Z-H, Stone CA, Jakubovic B, Phillips EJ, Sussman G, Park J, et al. Anti-PEG IgE in anaphylaxis associated with polyethylene glycol. J Allergy Clin Immunol Pr. 2020;in press.
9. Stone CAJ, Liu Y, Relling M V, Krantz MS, Pratt AL, Abreo A, et al. Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized. J Allergy Clin Immunol Pr. 2019;7(5):1533-1540.e8.
10. CSACI Statement on Pfizer/BioNTech Vaccine Anaphylaxis [Internet]. Available from: https://csaci.ca/wp-content/uploads/2020/12/PressRelease-Pfizer-COVID-19vaccine-DEC-14.pdf
11. Sellaturay P, Nasser S, Ewan P. Polyethylene Glycol-Induced Systemic Allergic Reactions (Anaphylaxis). J Allergy Clin Immunol Pr. 2020 Oct;in press.
12. Wenande E, Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin Exp Allergy. 2016 Jul;46(7):907–22.
13. Hamad I, Hunter AC, Szebeni J, Moghimi SM. Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway turnover and a MASP-2-dependent process. Mol Immunol. 2008 Dec;46(2):225–32.
14. NACI: Recommendations on the use of COVID-19 vaccine(s) [Internet]. Available from: https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines.html
15. COVID-19 Vaccine Testing & Administration Guidance for Allergists/Immunologists from the CSACI [Internet]. Available from: https://csaci.ca/wp-content/uploads/2021/01/COVID-19-VaccineTesting-AdministrationGuidance-JAN5.pdf
16. Government of Canada: Anaphylaxis and other Acute Reactions following Vaccination: Canadian Immunization Guide [Internet]. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-2-vaccine-safety/page-4-early-vaccine-reactions-including-anaphylaxis.html
17. Abrams EM, Greenhawt M. Special Article: Risk Communication During COVID-19. J Allergy Clin Immunol Pr. 2020;8:1791–4.
