COVID vaccine-associated allergic reactions

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

We have previously reported the primary clinical outcomes of our phase 2 randomized, double-blinded, placebo-controlled trial (COvid-19 Vaccine Associated Allergic Reactions trial; COVAAR) in which 16 participants who previously reported a systemic allergic reaction (SAR) to their first dose of a COVID-19 mRNA vaccine were randomly assigned to receive their second dose of Pfizer-BioNTech vaccine and placebo (saline) on consecutive days in a 1:1 blinded cross-over fashion in the Intensive Care Unit in the NIH Clinical Center. All participants received an open-label Pfizer-BioNTech booster in an outpatient clinic 5 months later. The median participant age was 45.5 years and all but one was female, consistent with the female predominance in reported anaphylactic reactions to COVID-19 vaccines. SARs recurred in only 2 (12.5%) subjects following both second and booster doses. Only one participant experienced a severe SAR, which was easily treated in an outpatient setting. No SARs occurred after placebo. While SARs were uncommon, clinical reactions following both placebo and vaccine doses were frequent. However, these reactions did not meet SAR criteria but were consistent with Immunization Stress-Related Response (ISRR), a non-allergic rapid onset clinical reaction due to the immunization process rather than vaccine components. ISRRs occurred after 62.5% of blinded vaccine doses, 75% of blinded placebo doses, and 75% of open-label booster doses. Overall, ISRRs occurred 5.5 times more often than SARs following placebo and vaccine doses. ISRRs had overlapping symptoms with allergic reactions including dizziness, throat and chest tightness, and abdominal pain. Both types of reactions had rapid onset (within minutes) after injection. However, the triad of neurological symptoms (most commonly paresthesias), acute heart rate and systolic blood pressure elevation, and absence of physical signs strongly suggested ISRR. In FY25, we examined the utility of the basophil activation test (BAT) in predicting SARs to the COVID-19 mRNA vaccines. Basophils play a key role in initiating allergic reactions by releasing inflammatory mediators following their activation and degranulation. In the BAT, whole blood is exposed to potential allergens, and activation of basophils is measured by upregulation of cell surface markers, including CD63. Blood samples from the 16 participants enrolled in COVAAR (collected before they received their second or booster doses), as well as 8 healthy volunteers who had tolerated the vaccine, were incubated with varying concentrations of BNT162b vaccine or the vaccine component dimyristoyl glycerol-polyethylene glycol 2000 (PEG 2000). We found that basophils from COVAAR and healthy controls responded similarly to both the vaccine and PEG-2000. Basophil responses also did not correlate with time lapse since the last vaccine administration or prior COVID-19 infection in either group. However, in both groups, CD63 upregulation following stimulation with the vaccine was greater among individuals who had received 2 or more doses of the vaccine compared to those who had only received a single dose. Our findings demonstrate that the BAT is not a reliable diagnostic tool to predict allergic reactions to COVID-19 mRNA vaccines, and that the number of previous vaccinations may confound interpretation of BAT results.