Clinical Phenotypes of Immediate First-Dose Reactions to mRNA COVID-19: A Multicenter Latent Class Analysis

Abstract

BackgroundAlthough immediate potentially allergic reactions have been reported after dose one of mRNA COVID-19 vaccines, comprehensively defined subtypes have not been clearly distinguished.ObjectiveTo define distinct clinical phenotypes of immediate reactions after dose one of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance.MethodsThis retrospective study included patients with ≥1 potentially allergic symptom or sign within 4 hours of receiving dose one of a mRNA COVID-19 vaccine and assessed by Allergy/Immunology specialists from 5 US academic medical centers (January-June 2021). We used latent class analysis – an unbiased, machine-learning modeling method – to define novel clinical phenotypes. We assessed demographic, clinical, and reaction characteristics associated with phenotype membership. Using log-binomial regression, we assessed the relation between phenotype membership and second dose tolerance, defined as either no symptoms or mild, self-limited symptoms resolving with antihistamines alone. A sensitivity analysis considered second dose tolerance as ‘objective signs only.’ResultsWe identified 265 patients with dose one immediate reactions with 3 phenotype clusters: 1) Limited/Predominantly Cutaneous, 2) Sensory and 3) Systemic. A total of 223 patients (84%) received a second dose and 200 (90%) tolerated their second dose. Sensory cluster (all patients had the symptom of numbness or tingling) was associated with a higher likelihood of second dose intolerance, but this finding did not persist when accounting for objective signs.ConclusionsThree novel clinical phenotypes of immediate-onset reactions after dose one of mRNA COVID-19 vaccines were identified using latent class analysis: 1) Limited/Predominantly Cutaneous, 2) Sensory and 3) Systemic. While these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it.