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Phenotypes of immediate mRNA COVID-19 vaccine reactions by machine learning

Published: September 12, 2022

Immediate, potentially allergic reactions after the first dose of mRNA coronavirus disease 2019 (COVID-19) vaccines were reported within days of the vaccine rollout, but subsequent clinical experiences showed that reaction were heterogeneous suggesting possible varying mechanisms. Almost all patients can be safely re-vaccinated with additional doses. Amongst these vaccine reactors, comprehensively defined subtypes had not been clearly distinguished, which presented an opportunity for using unbiased machine learning approaches to classify vaccine reactions.

A multicenter retrospective cohort study of first dose mRNA vaccine reactors was performed by Stone and Robinson et al., in The Journal of Allergy and Clinical Immunology: In Practice. With a multicenter dataset of patients evaluated by an allergist, machine learning was applied to the clinical symptoms and signs reported by 265 patients reporting an immediate-type first dose vaccine reaction. The multicenter cohort included sites at Massachusetts General Hospital, Brigham and Women’s Hospital, Vanderbilt University Medical Center, Yale School of Medicine, and University of Texas Southwestern Medical Center. The authors used unbiased machine learning methods to screen the reported symptoms and signs for hidden associations that would reveal distinct clusters. Such clusters could then be used as clinical phenotypes of immediate mRNA vaccine reactors to help clinicians with decision making and also inform future hypotheses about the mechanisms behind the reactions.

Of the 265 patients identified across the sites, (86%) were female, 204 (77%) had a history of prior atopy, and 54 (20%) reported a history of prior anaphylaxis. After machine learning was applied to the reported symptoms and signs of an immediate mRNA vaccine reaction, 3 phenotype clusters were identified. The clusters found that 70% of first dose reactors experienced Limited or Predominantly Cutaneous symptoms, followed by 17% who experienced primarily Sensory symptoms, and 13% who experienced Systemic symptoms. A total of 223 patients (84%) received a second dose of vaccine despite their initial reported reaction and 200 (90%) tolerated their second dose with minimal to no symptoms. The Sensory cluster (patients who predominantly reported symptoms of immediate onset numbness or tingling) was associated with a higher likelihood of reporting second dose intolerance, but this finding did not persist when accounting for objective signs.  

The authors consider these data useful for vaccine counseling and hypothesized these three clinical phenotypes represent different mechanisms for reacting to a first dose of mRNA COVID-19 vaccine.      

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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