COVID‐19 vaccines and anaphylaxis—evaluation with skin prick testing, basophil activation test and Immunoglobulin E

Abstract

To the Editor, Allergic reactions, including anaphylaxis, have been reported from the second day of Pfizer-BioNTech's COVID-19 vaccine administration in the mass vaccination programme. 1 Although the cause of these rare allergic reactions remains unclear, the excipient, polyethylene glycol (PEG), has been considered the culprit allergen. It is used as a stabilizer in the COVID-19 mRNA vaccines from Pfizer-BioNTech, 'Comirnaty', and Moderna, 'Spikevax'. A PEG-derivative polysorbate 80 is used in the adenovirus vector Oxford/AstraZeneca vaccine, 'Vaxzevria'. 2,3 Our aim was to present our experiences of evaluating 27 patients with systemic acute reactions to the first dose of COVID-19 vaccine plus 10 patients with suspected PEG allergy diagnosed before administration of the first vaccine dose. Our results indicate that a systemic acute reaction to the first dose, or to PEG or PEG derivatives, does not necessarily contraindicate a second dose of COVID-19 vaccine. 4,5 Thirty-seven patients were referred to, and evaluated at, the Allergy Center in Linköping, Sweden. The study was approved by the Swedish Ethical Review Authority, Dnr 2021-01301. Seven patients had an acute onset systemic reaction to the first dose of COVID-19 vaccine from Oxford/AstraZeneca, Vaxzevria, one to Spikevax (Moderna) and nineteen after the Pfizer-BioNTech vaccine, Comirnaty.

Anaphylaxis and Related Events Following COVID‐19 Vaccination: A Systematic Review

“…She later received the second dose without premedication. Similarly, Csuth et al 87 reported anaphylaxis in 7 female patients, 3 without any allergic history and 4 with allergies (most of them anaphylactic) to substances including food, wasp stings, latex, and drugs, and 1 male patient with a history of obesity, diabetes, cardiovascular disease, and anaphylactic allergy to multiple vaccines. These patients all had similar symptoms including respiratory symptoms (dyspnea, throat closure and swelling, and hoarseness), cardiovascular symptoms (tachycardia, hypotension), gastrointestinal symptoms (nausea, vomiting, generalized discomfort), and inflammatory symptoms (angioedema, pruritis, erythema).…”

“…Only 41 studies met our inclusion criteria 22,61–100 ; these consisted of 18 case series/reports, 18 cohort studies without control groups, and 4 cohort studies with control groups, one of which was a double‐blinded randomized clinical trial. The last study, Kaplan et al, 79 contained both a cohort analysis and a case series.…”

“…Some authors argue against receiving a second dose of the vaccine following the incidence of anaphylaxis after the first dose. However, Csuth et al, 87 Park et al, 94 and others recommend that such patients can undergo the skin prick tests and seek professional advice. Desensitization protocols such as that detailed by AlMuhizi et al 88 might also hold merit in allowing for more thorough vaccination in those with known allergies to the COVID‐19 vaccines.…”

Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID‐19 vaccines: A systematic review and meta‐analysis

“…This included a total of 317 individuals who underwent a total of 578 ST to one or more of the vaccines or vaccine excipients (not including dilutions). 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 Table 1 details the study characteristics, and Table E1 details the QUADAS‐2 risk of bias ratings for the included studies. All studies were designated as having unclear risk of bias due to performing only selected tests and/or the lack of blinding of test results though no study precluded vaccination based on a positive test; it was not possible in the current context to achieve a lower risk of bias.…”

“…For PEG (19 studies, 297 patients tested), test sensitivity was 0.02 (95%CrI 0.00–0.07) and test specificity was 0.99 (95%CrI 0.96–1) (Figure 4A ). 18 , 19 , 20 , 21 , 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 For PS (13 studies, 164 patients tested), testing sensitivity was 0.03 (95%CrI 0.00–0.11) and testing specificity 0.97 (95%CrI 0.91–1) (Figure 4B ). 18 , 19 , 21 , 24 , 25 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 Certainty of evidence was moderate (Table E2 ).One study did note several positive PS tests using Refresh Tears™ as a reagent, but this was an irritant and as such, positive PS tests to that reagent from that study were considered false positive.…”