key: cord-1026892-5o30qj0g authors: Csuth, Àgnes; Nopp, Anna; Storsaeter, Jann; Nilsson, Lennart; Jenmalm, Maria C. title: COVID‐19 vaccines and anaphylaxis—evaluation with skin prick testing, basophil activation test and Immunoglobulin E date: 2022-04-28 journal: Clin Exp Allergy DOI: 10.1111/cea.14143 sha: c0d0531104211966d7716bdf098aced67d785a40 doc_id: 1026892 cord_uid: 5o30qj0g nan 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, Five patients (patient number 5-9/ Table 1 ) had an acute onset systemic reaction with at least two different organ systems involved. These patients were treated with epinephrine, oral antihistamine and oral steroid. Their symptoms are described in Table 1 . including hypotension, vomiting, dizziness and decreasing saturation (from 95-96% to 91-93%). He was treated with intramuscular epinephrine, oral antihistamine, steroid tablets and oxygen. His tryptase level (14 µg/l) was not significantly elevated above his basal tryptase (13 µg/l). He was referred to a haematologist to evaluate suspected systemic mastocytosis, but the bone marrow biopsy did not show any evidence of such. Skin prick testing was carried out twice as a stepwise method, and all the SPTs were negative to PEG 300 (100%), /3000 (50%), /6000 (50%), /20,000 0.01%, 0.1%, 1%, 10% and 20%/ polysorbate 80 (20%)/poloxamer 407 (10%). The SPT to the undiluted Comirnaty vaccine was negative as well. BAT showed positive results for PEG 20,000 and 4000, and for the 10,000 were not detectable with the novel ImmunoCAP assays. 7 This patient had previously developed two suspected anaphylactic reactions after vaccinations, one of which contained polysorbate 80. A new risk-benefit evaluation was done; due to his cardiovascular disease, diabetes and obesity, a second dose was administered. He had premedication with desloratadine 10 mg, betamethasone 1 mg the day before and desloratadine 10 mg, betamethasone 1 mg and promethazine 25 mg on the day of the vaccination. The patient did not have any adverse reaction to the vaccination. Ten further patients (patient number: 10-19/ Table 1 Nine of these patients were treated with oral antihistamine and oral steroids, but not with epinephrine, and were referred to us for evaluation. All tested negative in skin prick testing with PEG and PEG derivatives and were vaccinated with the second vaccine dose with no adverse reactions. Two of the patients (20, 21) experienced shortness of breath without cardiovascular or dermatological symptoms after their first vaccine dose. The symptoms were described as asthma attacks. They used their previously prescribed short-acting beta-agonist inhalers to good effect. After negative skin prick testing, they received their second vaccine dose and tolerated it. Six of the patients (patient number: 22-27/ Table 1 ) reacted with acute onset (within 10-60 min after the first dose) skin symptoms such as urticaria or generalized erythema with or without pruritus with no other objective symptoms. Their skin prick tests for PEG and PEG derivatives were negative. One patient experienced generalized pruritus during skin prick testing, which did not worsen after the administration of the second vaccine dose. No severe objective symptoms were observed; one patient got slight redness on the chest. All six tolerated revaccination. All patients with acute onset urticaria, pruritus and angioedema after the first dose of the vaccine were treated with 10 mg desloratadine as premedication. Patients with underlying uncontrolled asthma who experienced breathing difficulties after the vaccination were advised to take a double dose of their regular asthma medication for a few days before the revaccination was administered. Ten patients were evaluated due to a previous severe reaction to medications, that is, injectable medicines containing PEG/ PEG derivatives, which raised suspicion of a PEG/PEG-derivative allergy (patient number: 28-37/ Table 2 ). All ten underwent skin prick testing with PEG and PEG derivatives, tested negative and were vaccinated with the Comirnaty vaccine with no severe allergic reactions. We did not observe any severe reactions in patients who were revaccinated, although the symptoms after the first vaccination were consistent with Level 2 or 3 of diagnostic certainty according to the Brighton Collaboration. This concurs with a recently published study by Wolfson et al. 9 Patients with acute onset urticaria, generalized erythema and pruritus also tolerated revaccination when allergy to PEG was ruled out. Patients with suspected severe PEG or PEGderivative allergy were successfully vaccinated as well. The Brighton Collaboration scoring system seems to overestimate the number of patients with clinically significant anaphylaxis. 9 One explanation may be that several subjective symptoms are included as minor criteria in the Brighton Collaboration scoring system. Although several patients experienced severe symptoms that were clinically consistent with anaphylaxis, revaccination could be administered without serious adverse events. Our findings suggest that anxiety-related non-immune factors may explain several of the reported anaphylaxis reactions. To end the devastating COVID-19 pandemic and limit mortality, as many as possible need to be safely vaccinated. 10 No conflict of interest to declare. All authors provided critical feedback and helped shape the re- The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. 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