Allergic reactions to current available COVID-19 vaccinations: pathophysiology, causality and therapeutic considerations

Abstract: Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, al-lergic reactions can occur during vaccination.Whereas such reactions are neither infrequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactionsthat are encoun-tered rarely but can cause serious complications.The allergic re¬sponses caused by vaccines can stem fromactivation of mast cells via Fcε receptor-1 type I reaction mediated by the interaction between IgE antibod¬ies against a particular vaccineand occur within minutes or up to 4 hours. The type IV allergic reactions initiate 48 hours after vaccination and demonstrate their peak be-tween 72 and 96 hours. Non-IgE-mediated mast cell degranulation via activation of the comple-ment system and via activation of the Mas-related G protein coupled receptor X2 can also induce allergic reactions. Inert substances, called excipients, that are added to vaccines for improve sta-bility and absorption, increase solubility, influence palatability, or create a distinctive appear-ance mainly and the active vaccine itself in a lesser extent can be the culprits. Polyethylene gly-col, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID19 mRNA vaccines and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID19 vaccines are excipients mostly incriminated for allergic reactions. This review will summarize the current state of knowledge of immediate and delayed allergic reactions in the currently available vaccines against COVID-19 together with the general and specific thera-peutic considerations, the incidence of allergic reactions and deaths with the available vaccines, the application of vaccination in patients with mast cell disease, the patients who developed al-lergy during the first dose, the vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, the deaths associated with COVID-19 vaccination and the questions arising in managing of this current ordeal. Careful vaccine-safety surveillance over time in conjunction with elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy. Allergists’ ex-pertise in the proper diagnosis and treatment of allergic reactions is vital for the screening of high-risk individuals.