Table 3.

Questions on How to Manage Those With a History of Anaphylaxis to a Vaccine Component or Anaphylaxis Following an mRNA Vaccine

Question	Pro	Con	General consensus
Is there a role of skin testing to PEG or PEG derivatives to guide initial or future doses of COVID-19 vaccines?	•If anaphylaxis to PEG exists, this will help define what products might be safe and what should be avoided in the future (molecular weight threshold)	•Mounting evidence supports that PEG skin testing is not helpful to determine vaccine tolerance69 •Patients with PEG anaphylaxis and positive skin test results to PEG have been tolerant of mRNA vaccines	• There is no role for PEG skin testing before administration of a COVID-19 vaccine • There is no role forPEG skin testing before administration of a COVID-19 vaccine in someone with a history of PEG allergy • There is no role for PEG skin testing alone following anaphylaxis to the first dose of a COVID-19 vaccine to guide future vaccine dosing. It is recommended instead that vaccine skin testing be done • PEG skin testing should be used in an individual suspected to have PEG anaphylaxis regardless of COVID-19 vaccine exposure or tolerance to help guide PEG-containing drugs and products that the individual should avoid.
Is there a role of skin testing to COVID-19 vaccines to guide initial or future doses of COVID-19 vaccines?	•Prick testing to vaccines is an established procedure to help guide management.93 •Non-irritating concentrations (undiluted for mRNA vaccines) for prick and intradermal testing have been reported.72 , 73 •If testing for more than one COVID-19 vaccine, a positive test result to one and a negative result to another may give a vaccination strategy.	•Negative vaccine responses have occurred in those with positive immediate skin test results raising the question of positive predictive value. •Delayed responses (not relevant to an allergic response) at the skin test site may be relevant in those who have had at least dose 1 or prior natural infection. •Does not give any indication of tolerance of PEG in drugs or injectables and patients with PEG anaphylaxis as they can be negative on skin testing to mRNA vaccines and require additional follow-up and PEG specific testing to determine PEG product avoidance.	• There is no role for skin testing before administration of a COVID-19 vaccine •It is recommended that COVID-19 vaccine challenge whether it be to the same or different mRNA vaccine or a different vaccine platform (eg, adenoviral vector) be done under the allergist observation.
Is there a role for administering a future dose with a different COVID-19 vaccine platform	•Provides a strategy based on those used with vaccine allergy in the past. •Some evidence in small studies to support robust immunologic response using heterologous vaccine platform. •Can be an allergist observed procedure with the decision shared with the patient.	•Data on the efficacy and safety of such procedures have not been established and have typically favored better response with mRNA vaccine following adenoviral vector vaccine. •Vaccination with a new platform or different vaccine (eg, adenoviral vector vaccine) could be associated with age- and demographic-related adverse events that are not as easily treated as anaphylaxis (eg, thrombosis with thrombocytopenia with adenoviral vector vaccines or myocarditis with mRNA vaccines).	•Increasing evidence supports that most patients with an mRNA vaccine reaction will tolerate repeat dosing with an mRNA and the decision of whether to administer an alternative mRNA vaccine vs the same mRNA vaccine vs a new platform (eg, Johnson & Johnson or AstraZeneca) should be shared with the patient.
Is there a role for graded dosing of a COVID-19 vaccine	•This is an established approach that allergists have used with other vaccines to challenge in the face of a suspected component or previous vaccine reaction.	•mRNA vaccines are a new vaccine platform and the Pfizer-BioNTech vaccine in particular is low in volume. It is not known the impact that graded dosing might have on vaccine efficacy.	•Shared decision with the patient for rechallenge is recommended. Regardless of how the vaccine is administered in the setting of prior anaphylaxis, allergist-observed vaccination is recommended. Observed full-dose vaccination has been well tolerated even in the setting of first-dose anaphylaxis.
Is there a role to check SARS-CoV-2 antibodies to guide future dosing?	•Antibodies may give some information about a response to vaccine (Spike) or natural infection (Nucleocapsid-RBD).	•Although our knowledge is advancing, the specific immune correlates of protection are not known and include a complex equation of both antibody and T-cell responses. An antibody response does not take into account the importance of T-cell responses. •Antibody responses are not predictably helpful with the presence of new viral variants.	•Measuring antibody responses is generally not helpful to guide initial or future vaccination and could give false reassurance given the importance of booster doses for protection of new viral variants, such as omicron.
Should COVID-19 vaccination be deferred in someone who has had a history of a component reaction or first or second dose reaction?	•COVID-19 monoclonal antibodies have been approved that provide passive immunity giving a buffer of time to make the decision on the safest management.	•COVID-19 monoclonal antibodies approved for preexposure prophylaxis (tixagevimab/cilgavimab [Evusheld]) are in short supply and ideally should be reserved for our patients with primary or secondary immunodeficiencies likely to have inferior vaccine response. In addition, they are not a replacement for vaccination and all patients who receive Evusheld should have had vaccination attempted. •Monoclonal antibodies may not be active against future variants. •Most patients with a component reaction tolerate COVID-19 mRNA vaccines. •Most patients with a first or second dose anaphylactic reaction tolerate subsequent dosing.	•With careful allergist assessment, there should be no need to unnecessarily delay COVID-19 vaccination in either initial series or booster based on a prior reaction. This should be shared with the patient and follow the principles outlined previously.

Abbreviations: COVID-19, coronavirus disease 2019; mRNA, messenger ribonucleic acid; PEG, polyethylene glycol; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.