Risk stratification through extensive allergy work-up in COVID-19-mRNA vaccine allergic reactions

Polyethylene glycol (PEG) allergies through IgE activation and a complement activation-related pseudoallergy mechanism have been suggested during reactions to COVID-19-mRNA vaccines. Reported allergy work-up and outcomes of subsequent COVID-19 vaccinations in patients with a suspicion of hypersensitivity to COVID-19-mRNA vaccines to determine risk factors for anaphylaxis at the next dose. In total, 190 patients were referred to two European allergy centers for suspicion of hypersensitivity to COVID-19-mRNA. These patients have been an allergy work-up [skin tests (ST) with COVID-19-mRNA vaccine and PEGs with different molecular weight, and basophil activation tests (BAT) to PEG-2000]. Immediate, delayed reactions compatible with hypersensitivity and reactions not suggestive of hypersensitivity, after a detailed analysis of the medical history, were reported in 69, 84 and 37 patients, respectively. Thirty-one cases with index anaphylaxis (16%); with only 3 severe anaphylaxis, all occurred within one hour after vaccine administration. One hundred and sixty patients (84%) were revaccinated with good tolerance in 139 cases (87%). In 145 patients, revaccination was performed with the culprit vaccine, which was well tolerated in 126 of the patients; with an alternative COVID-19 vaccine (other mRNA vaccine for 12) in 15, well tolerated in 13. Among the 31 patients reporting index anaphylaxis, 23 were revaccinated with the culprit vaccine under hospital supervision, with good tolerance in 15 (65%). The eight immediate reactions after revaccination were less severe than the index one. The work-up was positive in 9 patients (4.7%); among them, four tolerated the culprit vaccine (n = 1) or another COVID-19 vaccine (n = 3), and five refused further vaccination. Our results are in accordance with the literature and with ENDA/EAACI recommendations for allergies to COVID-19 vaccines. Although more studies are needed to determine the ST and BAT predictive value. This series strongly argues for re-vaccinating in suspected vaccine allergies. And we suggest to refer for allergy work-up only patients with reactions occurring within the first hour after COVID-19-mRNA vaccine administration.