Table I.

Summary recommendations

Question	Recommendation	Recommendation trength	Evidence ertainty
What is the risk of SARS-CoV-2 vaccine anaphylaxis in a patient with no history of anaphylaxis to a SARS-CoV-2 vaccine or its excipients?	For patients with no history of a previous severe allergic reaction to a SARS-CoV-2 vaccine or its excipients, the risk of SARS-CoV-2 vaccine–induced anaphylaxis is very rare and we recommend vaccination over no vaccination based on this risk.	Strong	High
	For patients with a history of a severe allergic reaction, including anaphylaxis, unrelated to a SARS-CoV-2 vaccine or excipient but no history of a previous severe allergic reaction to a SARS-CoV-2 vaccine or its excipients, the requirement for additional observation beyond standard wait time (eg, recommended by local health authorities for the general population) provides a minimal absolute risk reduction in severe allergic reaction outcomes and may also contribute to vaccine hesitancy. Therefore, we suggest against prolonged observation in those with a history of severe allergic reactions unrelated to a SARS-CoV-2 vaccine or excipient.	Conditional	Low
In patients without a history of anaphylaxis to a SARS-CoV-2 vaccine or its excipients, should allergy skin testing to SARS-CoV-2 vaccines or its excipients be performed?	In patients with no history of a severe allergic reaction, including anaphylaxis, to SARS-CoV-2 vaccines or its excipients, we recommend against vaccine or vaccine excipient testing prior to vaccination in an attempt to predict the rare individual who will have a severe allergic reaction to vaccination.	Strong	Low
In patients with a history of anaphylaxis to a SARS-CoV-2 vaccine or its excipients, should allergy skin testing to SARS-CoV-2 vaccines or its excipients be performed to determine whether vaccine withholding is needed?	We suggest against the clinician routinely performing skin or in vitro testing using SARS-CoV-2 vaccines or excipients outside of the research setting for the purpose of vaccine withholding, given such testing has unknown sensitivity/specificity in predicting severe allergic reactions, including anaphylaxis, to SARS-CoV-2 vaccines.	Conditional	Low
Should SARS-CoV-2 mRNA or adenovirus-vector vaccines be administered to an individual who had an immediate allergic reaction to the first dose of the vaccine (defined as a generalized, systemic allergic reaction with acute onset occurring within 4 hours of vaccine administration) or given as a first dose to an individual who is suspected to have reacted previously to an excipient ingredient that is also present in the SARS-CoV-2 mRNA or adenovirus-vector vaccines?	We recommend a shared decision-making paradigm of care favoring vaccination through full or graded dosing (with or without additional observation time postvaccination) or changing vaccine platforms to another agent over no vaccination because there is no single best approach to assessment and management of the patient with a suspected SARS-CoV-2 mRNA or adenovirus-vector vaccine reaction or the patient with an allergy to an excipient in either of these vaccines who has not yet been vaccinated.	Strong	Moderate
	In patients with a suspected immediate allergic reaction to SARS-CoV-2 vaccine whose standard schedule requires more than 1 dose, we recommend referral to an allergist for assessment of additional vaccination over no vaccination/vaccination being withheld. In resource-limited settings in which specialist referral is not readily available, alternatives may be presented in a shared decision-making context to provide assessment and opportunity for vaccination by remote consultation, use of alternative vaccine products, or delay in vaccination until a solution can be determined.	Strong	Moderate
	In patients with a suspected or confirmed but remote past medical history of reaction to a SARS-CoV-2 vaccine excipient, we recommend referral to an allergist for assessment of additional vaccination over no vaccination/vaccination being withheld. In resource-limited settings in which specialist referral is not readily available, alternatives may be presented in a shared decision-making context to provide assessment and opportunity for vaccination by remote consultation, use of alternative vaccine products, or delay in vaccination until a solution can be determined.	Strong	Moderate
	In patients with a definite/confirmed recent allergic reaction to SARS-CoV-2 vaccine and/or excipient, we recommend referral to an allergist for assessment of additional vaccination over no vaccination/vaccination being withheld. In resource-limited settings in which specialist referral is not readily available, alternatives may be presented in a shared decision-making context to provide assessment and opportunity for vaccination by remote consultation, use of alternative vaccine products, or delay in vaccination until a solution can be determined.	Strong	Low
	Whereas all vaccines should be administered in facilities capable of treating anaphylaxis, particularly for individuals with a prior immediate systemic allergic reaction to a SARS-CoV-2 vaccine or vaccine excipient, we recommend the clinician should administer SARS-CoV-2 mRNA or adenovirus-vector vaccine in a setting equipped to manage anaphylaxis (eg, hospital, mass immunization clinic, specialist office), under the supervision of personnel trained in the recognition and management of anaphylaxis. In resource-limited settings in which specialist referral is not readily available, alternatives may be presented in a shared decision-making context to provide assessment and opportunity for vaccination by remote consultation, use of alternative vaccine products, or delay in vaccination until a solution can be determined.	Strong	Moderate
	We suggest against routine H1-antihistamine or systemic corticosteroid premedication prior to vaccination because it has low-certainty evidence in preventing anaphylaxis, and theoretically, corticosteroid premedication could diminish the immune response.	Conditional	Low
	We recommend in favor of globally coordinated research studies being conducted to address (1) vaccine and vaccine excipient testing diagnostic accuracy for allergy to SARS-CoV-2 vaccines; (2) administration of the vaccine to individuals with prior anaphylaxis to the vaccine or vaccine excipient; (3) the necessity and efficacy of graded vaccine administration in the context of a patient with possible SARS-CoV-2 vaccine allergy; (4) the safety, efficacy, and necessity of mixing SARS-CoV-2 vaccine platforms; and (5) the incremental benefit of additional doses of an mRNA or certain adenovirus-vector vaccines following an initial dose.	Research recommendation