A year of research establishes COVID-19 vaccine safety among patients with allergies

The allergy and immunology community has achieved significant and hopeful progress in its understanding of allergic reactions to mRNA COVID-19 vaccines, according to a review published in The Journal of Allergy and Clinical Immunology.

Although reports of anaphylaxis accompanied the earliest administered doses in December 2020, evidence now shows that these cases are rare, Aleena Banerji, MD, associate professor at Harvard Medical School and clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital, and colleagues wrote in the review.

Early in the vaccines’ rollout, the authors wrote, the polyethylene glycol (PEG) 2000 molecule that stabilizes the lipid nanoparticle carrier of the active mRNA that encoded the SARS-CoV-2 spike protein was suggested as the trigger for immediate allergic reactions to these vaccines.

The CDC and FDA as well as international regulatory bodies initially recommended that individuals with PEG allergies abstain from mRNA vaccination. However, research has since found that people with previous anaphylactic reactions to PEG or PEG derivatives can tolerate mRNA vaccines.

Also, the authors wrote, people who presumably had an anaphylactic reaction to the first dose of an mRNA vaccine largely tolerate second and booster doses, suggesting mechanisms that were not mediated by IgE.

In fact, the authors wrote, many of those immediate reactions to the first dose were experienced without any objective hypersensitivity symptoms and were vasovagal, symptomatic stress reactions, reactogenic or syncopal instead of allergic.

The authors also wrote that patients who have a reaction to an mRNA vaccine do not need PEG skin testing, which could delay vaccination completion. Many of these patients have safely tolerated subsequent doses as well, with allergist oversight.

Further, the authors pointed to the need to reduce vaccine hesitancy among those patients with an allergy history. Booster shots reduce disease severity among patients who contract variants such as delta and omicron, the authors wrote. Also, there is now a short supply of new monoclonal antibodies used for acute treatment or preexposure prophylaxis of COVID-19 omicron cases. 

Some theoretical evidence indicates that PEG IgM and IgG could cause non-IgE mediated mechanisms, although the authors called such tests unlikely to be useful in predicting mRNA vaccine reactions.

Additionally, some people may have reactogenic symptoms associated with the vaccines’ active components that unmask underlying tendencies toward non-IgE mediated mast cell activation. Underlying anxiety about vaccination and other diverse factors may trigger nonallergic symptoms as well.

Although true reactions to mRNA vaccines are rare, the authors continued, doctors should observe vaccination and manage these cases carefully while considering skin prick testing to PEG and to the vaccines.

The authors also called for allergists to comprehensively work up individuals who have a history of PEG anaphylaxis regardless of whether they have tolerated mRNA vaccines, as they are still at risk for potentially fatal anaphylaxis due to PEG3350, which has a higher molecule weight.

Noting that allergy almost is never a reason for exemptions to the COVID-19 vaccines, the authors wrote that no history including food, drug, vaccine or other allergies is a contraindication for vaccination.

Finally, the authors wrote that shared decision-making is key and encouraged doctors to cite published data about tolerance of mRNA vaccines despite prior reactions when discussing the risks and benefits of vaccination with their patients.