Immediate hypersensitivity to COVID-19 vaccines: Focus on biological diagnosis

Abstract

Soon after the release of the new anti-COVID mRNA vaccines, reports came in from the US and the UK of anaphylactic reactions. Fueled by the necessary caution toward these new vaccine platforms, these reports had a great impact and were largely commented upon in the scientific literature and global media. The current estimated frequency is of 5 cases per million doses. Very little biological data are presented in the literature to support the anaphylaxis diagnosis in these patients in addition to skin tests. Allergic reactions to vaccines are rare and mostly due to vaccine excipient. Therefore, the poly-ethylene-glycol (PEG) present in both mRNA formulation, and already known to be immunogenic, was soon suspected to be the potential culprit. Several hypersensitivity mechanisms to PEG or to other vaccine components can be suspected, even if the classical IgE-dependent anaphylaxis seems to be one of the most plausible candidates. In the early 2022, the international guidelines recommended to perform skin prick tests and basophil activation tests (BAT) in people experiencing allergic reaction to the first dose of COVID-19 vaccine or with a history of PEG allergy. The aim of this review is to discuss the main potential mechanisms of immediate allergy to COVID19 vaccines based on published data, together with the various techniques used to confirm or not sensitization to one component.

Keywords: COVID-19 vaccine; IgE; anaphylaxis; basophil activation test; complement.

Figure 1

Legend. Main mechanisms of potential COVID-19 vaccine-induced hypersensitivity. The classical mechanism involves specific IgE-dependent mast cell and basophil activation leading to histamine/tryptase release. The alternative or additional mechanism involves specific IgG-dependent neutrophil activation leading to the release of reactive oxygen species (ROS), proteases such as elastase or neutrophil extracellular traps (NETs). Finally, several other mast cell activation mechanisms are suspected to play a role via C3a or C5a fixation to their receptors, or via the direct activation of MRGPRX2 by the vaccine.