mRNA Vaccines to Prevent COVID-19 Disease and Reported Allergic Reactions: Current Evidence and Suggested Approach

Abstract

The U.S. Food and Drug Administration (FDA) has recently issued an Emergency Use Authorization (EUA) for 2 highly effective coronavirus disease 2019 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. This has brought hope to millions of Americans in the midst of an ongoing global pandemic. The FDA EUA guidance for both vaccines is to not administer the vaccine to individuals with a known history of a severe allergic reaction (eg, anaphylaxis) to any component of the COVID-19 vaccine. The Centers for Disease Control and Prevention (CDC) additionally advises individuals with a history of an immediate allergic reaction to a vaccine or injectable or any history of anaphylaxis be observed for 30 minutes after COVID-19 vaccination. All other individuals should be observed for 15 minutes after COVID-19 vaccination. Staff at vaccine clinics must be able to identify and manage anaphylaxis. Post-FDA EUA, despite very strong safety signals in both phase 3 trials, reports of possible allergic reactions have raised public concern. To provide reassurance and support during widespread global vaccination, allergists must offer clear guidance to individuals based on the best information available, but also in accordance with the broader recommendations of regulatory agencies. This review summarizes vaccine allergy epidemiology and proposes drug and vaccine allergy expert opinion informed risk stratification for Allergy specialist use in conjunction with guidance of public health and regulatory authorities. The risk stratification schema guide care for (1) individuals with different allergy histories to safely receive their first mRNA COVID-19 vaccine and (2) individuals who develop a reaction to their first dose of mRNA COVID-19 vaccine.

Keywords: Allergic reactions; Allergy; Anaphylaxis; COVID-19; Guidelines; Polyethylene glycol; Polysorbate; Risk stratification; Vaccine; mRNA.

Figure 1

Chemical structure and similarities between PEG and polysorbate 80.

Figure 2

Risk stratification pathways with categories based on Mass General Brigham and Vanderbilt allergy expert consensus before initial COVID-19 vaccination. ∗If “yes” for questions 1 or 2, specific investigation as to the specific injectable products and vaccines should be pursued to determine whether these products could have contained high-molecular-weight PEG, polysorbate, or polyoxyl 35 castor oil (paclitaxel). See Tables II, III, and IV. ¶Current CDC guidance suggests 30 minutes of observation for patients with any history of anaphylaxis. §See Figures 3 and 4 for expanded skin testing procedures and non-irritating skin test concentrations. If skin testing to PEG is positive, as of December 28, 2020, Pfizer-BioNTech and Moderna are the only FDA approved vaccines and under EUA can not be given to an individual with a history of anaphylaxis to a component of the COVID-19 mRNA vaccine. Skin testing to polysorbate 20 and 80 become more important for patients with confirmed severe PEG allergy with regards to the safety of future vaccinations.

Figure 3

Expanded skin testing procedure. ∗Recommended skin testing to evaluate only known potential IgE mechanism (PEG allergy). ¶Skin testing for consideration to evaluate PEG and polysorbate allergy. In patients with positive PEG skin testing, the result of polysorbate 20 and 80 skin testing becomes important with regards to the safety of future SARS-CoV-2 vaccines in development. Therefore, based on clinical history, skin testing to both PEG and polysorbate during 1 clinic visit may be appropriate. §Anaphylaxis with intradermal skin testing in PEG allergic patients has been described. We recommend staff have anaphylaxis training and anaphylaxis kit available in close proximity. ‡Tables II, III, and IV contain a list of PEG/polysorbate containing vaccines and injectables that can be shared with patients. ∗∗Recommended only after shared decision making between allergist and patient.

Figure 4

Nonirritating skin testing concentrations for PEG3350 and polysorbate. ∗Methyl-prednisolone sodium succinate does not contain PEG or polysorbate 80 and can be used as an additional control. ¶Refresh Optive Advanced Lubricant eye drops and Prevnar are an alternate source for polysorbate 80 skin testing. §Some brands of methylprednisolone acetate contain polysorbate and PEG3350 while others only have PEG3350; use methylprednisolone acetate containing PEG3350 only. ‡Nonirritating skin testing concentrations for methyl-prednisolone sodium succinate and triamcinolone acetonide include a range of 10 to 40 mg/mL for initial skin prick testing with subsequent 10× dilutions. One author (E.P.) has extensive experience using 50 mg/mL as a non-irritating skin testing concentration for methyl-prednisolone sodium succinate skin prick testing with subsequent 10× dilutions. ∗∗Dissolve 17 gram miralax packet in 100mL of sterile water for 1:1 solution (170 mg/mL).

Figure 5

Risk stratification pathways with categories based on Mass General Brigham and Vanderbilt allergy expert consensus after allergic reaction to first dose of COVID19 vaccine. ∗Ideal laboratory assessment includes reaction serum tryptase within 2 hours and complement activation by ELISA (C3a, C3b, C5a, C5b-9 ideally within 1 hour; send to National Jewish); follow-up baseline serum tryptase is also useful. ¶Follow CDC guidance. §See Figures 3 and 4 for expanded skin testing algorithm and nonirritating skin test concentrations. ‡Shared decision making with allergist considering eligibility for second dose or future challenge with other SARS-CoV-2 vaccines. There are no data on the safety of administering the second vaccine dose after potential anaphylaxis to the first dose and limited anecdotal evidence from the authors’ clinical experience suggesting that some patients can safely receive the second dose after more mild allergic type reactions to the first dose. If the decision is made to proceed with vaccination, staff should have anaphylaxis training and anaphylaxis kit needs to be available in close proximity. ∗∗84% (147/175) of potential anaphylaxis cases reported to the CDC were unconfirmed after their case review. ¶¶PEG skin testing can be considered to assist in the evaluation of a potential IgE mechanism but data confirming this mechanism is responsible for reported reactions to mRNA COVID-19 vaccines are lacking. §§Consider 15 or 30 minute observation based on clinical judgment.

Figure 6

Graphic to assist in the recognition of anaphylaxis.BP, Blood pressure; GI, gastrointestinal.