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, allergic reactions can occur during vaccination.While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactionsthat are encountered rarely, but can cause serious complications.The allergic responses caused by vaccines can stem fromactivation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. The type IV allergic reactions initiate 48 h after vaccination and demonstrate their peak between 72 and 96 h. Non-IgE-mediated mast cell degranulation via activation of the complement system and via activation of the Mas-related G protein-coupled receptor X2 can also induce allergic reactions. Reactions are more often caused by inert substances, called excipients, which are added to vaccines to improve stability and absorption, increase solubility, influence palatability, or create a distinctive appearance, and not by the active vaccine itself. Polyethylene glycol, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID-19 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 therapeutic considerations. These considerations include:The incidence of allergic reactions and deaths under investigation with the available vaccines, application of vaccination in patients with mast cell disease, patients who developed an allergy during the first dose, vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, deaths associated with COVID-19 vaccination, and questions arising in managing of this current ordeal.Careful vaccine-safety surveillance over time, in conjunction with the elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy.Allergists’ expertise in proper diagnosis and treatment of allergic reactions is vital for thescreening of high-risk individuals.

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…A DVT has also been reported shortly after the second dose of an mRNA-based vaccine as well [ 52 ]. Anaphylaxis as an acute allergic reaction has also been reported as a rare event for some vaccines, such as mRNA COVID-19 vaccines [ 53 ] and adenovector vaccines against COVID-19 [ 54 ]. Overall, these severe life-threatening adverse events are occurring rarely, thus supporting the ongoing rollout of global vaccination programs.…”

The Immunogenicity of Hyaluronic Fillers and Its Consequences

“… 78 The compound is present in COVID-19 vaccines, because the introduction of a pegylated nanoparticle surrounding mRNA impairs its enzymatic degradation, increases its water-solubility and, thereby, the bioavailability of lipid nanoparticles. 75 , 79 Despite the fact that PEGs are considered to be compounds with the low potential of triggering allergic reactions, the most commonly described hypersensitivity reactions were IgE-dependent. Moreover, some authors reported cases of anaphylactic shock and complement activation-related pseudoallergy.…”

Type 1 Kounis Syndrome Induced by Inactivated SARS-COV-2 Vaccine

“…This syndrome has been associated with several diseases, a variety of drugs or environmental exposures [8]. Although vaccine ingredients may be considered potential inducers of allergic events [9], KS induced by vaccines is a very rare clinical condition. Only few cases of allergic myocardial infarction due to tetanus and influenza vaccines have been previously reported [10,11].…”