Rapid progress in our understanding of COVID-19 vaccine allergy: A cause for optimism, not hesitancy

Abstract

Anaphylaxis is a life-threatening condition and when associated with vaccination, leads to vaccine hesitancy. The concerns around vaccine-related anaphylaxis have become even more important during the coronavirus disease 2019 (COVID-19) pandemic where the COVID-19 vaccines remain one of our most important tools. Although rates of anaphylaxis to COVID-19 vaccines are not significantly different from those to other vaccines, Centers for Disease Control and Prevention guidance recommends avoidance of the same COVID-19 vaccine in individuals who had an allergic reaction or are allergic to a COVID-19 vaccine component. Fortunately, our understanding of COVID-19 vaccine allergic reactions has improved dramatically in the past year in large part due to important research efforts from individuals in the allergy community. Initially, researchers published algorithmic approaches using risk stratification and excipient skin testing. However, as our experience and knowledge improved with ongoing research, we have better data showing safety of repeat vaccination despite an initial reaction. We review our progress starting in December 2020 when the Food and Drug Administration approved the first COVID-19 vaccine in the United States through early 2022, highlighting our success in understanding COVID-19 vaccine reactions.

Keywords: COVID-19; allergy; anaphylaxis; mRNA; polyethylene glycol; vaccine.

Fig 1

Rapid progress in our understanding of COVID-19 vaccine allergy. CDC, Centers for Disease Control and Prevention; EUA, Emergency Use Authorization; FDA, Food and Drug Administration; NHS, National Health Service.

Fig 2

A, Clinical approach to PEG allergy. This algorithm can be used in individuals reporting a clinical history consistent with anaphylaxis to PEG including a PEG injectable or oral (eg, Miralax); tolerance of mRNA vaccines does not delabel a PEG allergy, and comprehensive PEG allergy evaluation is required following mRNA vaccination to guide the individual safely of PEG products. When advising COVID-19 vaccination, current CDC recommendations are to receive mRNA vaccines if possible due to known risk of thrombosis with thrombocytopenia with adenoviral vector vaccine, Janssen. CDC, Centers for Disease Control and Prevention; ST, skin testing. ∗Use mRNA COVID-19 vaccine nonirritating skin testing concentration. †Consider proceeding with the mRNA COVID-19 vaccine that was not responsible for clinical vaccine reaction (eg, Moderna if clinical reaction was to Pfizer). Negative mRNA COVID-19 vaccine challenge has been described in the setting of positive skin prick testing result to the mRNA vaccines; full dose (0.3 mL/0.2 mL for Pfizer-BioNTech for ≥12 and children 5-11 years old and 0.5 mL for Moderna) is suggested because of lack of data on the efficacy of split-dose mRNA vaccination. Negative challenge to both the mRNA vaccines and the adenoviral vector vaccines has been described in the setting of a positive intradermal skin test result to polysorbate 80. B, Clinical approach to mRNA vaccine allergy. Excipient differences over time between mRNA vaccines: the original Pfizer-BioNTech vaccine distributed (purple cap) for the 12 years or older age group was PBS buffered (purple cap). These have now been replaced with a tris buffered (gray cap) version; the pediatric (orange cap) 10 μg, 0.2 mL intramuscular formulation is also tris buffered. Moderna vaccine is tris buffered. ^∗There are no contraindications to receive subsequent COVID-19 mRNA vaccination for any other adverse events. Severe cutaneous adverse reactions or severe rash with systemic symptom has rarely been seen in temporal association with COVID-19 vaccinations. †Consider PEG skin prick testing if clinically relevant. If PEG skin prick testing result is positive, proceed with patient counseling regarding avoidance of medications containing PEG. ‡Consider proceeding with the mRNA COVID-19 vaccine not responsible for clinical vaccine reaction (eg, Moderna if clinical reaction was to Pfizer). Negative mRNA COVID-19 vaccine challenge has been described in the setting of positive skin prick testing result to the mRNA vaccines; full dose is suggested because of lack of data on the efficacy of split-dose mRNA vaccination. Negative challenge to both the mRNA vaccines and the adenoviral vector vaccines has been described in the setting of a positive intradermal skin test result to polysorbate 80.

Fig 2

A, Clinical approach to PEG allergy. This algorithm can be used in individuals reporting a clinical history consistent with anaphylaxis to PEG including a PEG injectable or oral (eg, Miralax); tolerance of mRNA vaccines does not delabel a PEG allergy, and comprehensive PEG allergy evaluation is required following mRNA vaccination to guide the individual safely of PEG products. When advising COVID-19 vaccination, current CDC recommendations are to receive mRNA vaccines if possible due to known risk of thrombosis with thrombocytopenia with adenoviral vector vaccine, Janssen. CDC, Centers for Disease Control and Prevention; ST, skin testing. ∗Use mRNA COVID-19 vaccine nonirritating skin testing concentration. †Consider proceeding with the mRNA COVID-19 vaccine that was not responsible for clinical vaccine reaction (eg, Moderna if clinical reaction was to Pfizer). Negative mRNA COVID-19 vaccine challenge has been described in the setting of positive skin prick testing result to the mRNA vaccines; full dose (0.3 mL/0.2 mL for Pfizer-BioNTech for ≥12 and children 5-11 years old and 0.5 mL for Moderna) is suggested because of lack of data on the efficacy of split-dose mRNA vaccination. Negative challenge to both the mRNA vaccines and the adenoviral vector vaccines has been described in the setting of a positive intradermal skin test result to polysorbate 80. B, Clinical approach to mRNA vaccine allergy. Excipient differences over time between mRNA vaccines: the original Pfizer-BioNTech vaccine distributed (purple cap) for the 12 years or older age group was PBS buffered (purple cap). These have now been replaced with a tris buffered (gray cap) version; the pediatric (orange cap) 10 μg, 0.2 mL intramuscular formulation is also tris buffered. Moderna vaccine is tris buffered. ^∗There are no contraindications to receive subsequent COVID-19 mRNA vaccination for any other adverse events. Severe cutaneous adverse reactions or severe rash with systemic symptom has rarely been seen in temporal association with COVID-19 vaccinations. †Consider PEG skin prick testing if clinically relevant. If PEG skin prick testing result is positive, proceed with patient counseling regarding avoidance of medications containing PEG. ‡Consider proceeding with the mRNA COVID-19 vaccine not responsible for clinical vaccine reaction (eg, Moderna if clinical reaction was to Pfizer). Negative mRNA COVID-19 vaccine challenge has been described in the setting of positive skin prick testing result to the mRNA vaccines; full dose is suggested because of lack of data on the efficacy of split-dose mRNA vaccination. Negative challenge to both the mRNA vaccines and the adenoviral vector vaccines has been described in the setting of a positive intradermal skin test result to polysorbate 80.