Initial guidelines advised that sensitization to PEG should be taken into consideration in suspected subjects before a recommendation on the administration of vaccines for COVID-19 containing PEG or its cross-reactive analogues. 3 However, PEG shows an important variability in terms of molecular weights and conjugation forms. In that sense, although it is known that PEG-2000 (MW: 2000g/mol) conjugated with lipids is the form contained in the vaccines for COVID-19, there has been great variability in the PEG molecules used in allergy tests to evaluate sensitization of suspected subjects in the context of the current COVID-19 vaccination campaigns. 4 In this context, recent findings have shed light on the specific form of PEG that could be responsible of the hypersensitivity reactions to the mRNA vaccines for COVID-19.

Following the emergency use authorization of the vaccine mRNA-1273 on 18th December 2020 in the US and the vaccine BNT162b2 one week earlier, two mRNA vaccines are in currently used for the prevention of coronavirus disease 2019 (COVID-19). Phase 3 pivotal trials on both vaccines excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and in the US, anaphylactic reactions have been reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000), which is contained in both vaccines as PEG-micellar carrier system as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEG-ylated lipids are rarely IgE-mediated, but may result from complement activation-related pseudoallergy (CARPA) that has been described to similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to e.g. gadolinium-based or iodinated contrast media. Skin prick-, intradermal-, epicutaneous- tests, in vitro sIgE assessment, evaluation of sIgG/IgM, as well as basophil activation test are in use to demonstrate allergic reactions to various components of the vaccines.

COVID-19 vaccines and the role of other potential allergenic components different from PEG. A reply to: “Other excipients than PEG might cause serious hypersensitivity reactions in COVID-19 vaccines”

Title: COVID-19 vaccine anaphylaxis: IgE, complement or what else? A reply to: “COVID-19 vaccine anaphylaxis: PEG or not?”

A document by Natalija Novak. Click on the document to view its contents.

The pandemic condition Coronavirus-disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Different clinical symptoms caused by involvement of organs outside the respiratory system have been also described. Interestingly, reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2 positive patients as such features outside the respiratory sphere, are rapidly emerging. However, knowledge about prevalence and pattern of skin involvement, time of onset, predilection, and its direct or indirect relation to SARS-CoV-2 is still limited. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors and describe differential diagnostic evaluations.