Study of Excipients in Delayed Skin Reactions to mRNA Vaccines: Positive Delayed Intradermal Reactions to Polyethylene Glycol Provide New Insights for COVID-19 Arm

Background: Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. Methods: Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. Results: Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. Conclusions: Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice.