@article{3e21d0983eb44d54aca70fec1ae94cbb,
title = "Clinical Phenotypes of Immediate First-Dose Reactions to mRNA COVID-19: A Multicenter Latent Class Analysis",
abstract = "Background: Although immediate potentially allergic reactions have been reported after dose 1 of mRNA coronavirus disease 2019 (COVID-19) vaccines, comprehensively defined subtypes have not been clearly distinguished. Objective: To define distinct clinical phenotypes of immediate reactions after dose 1 of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance. Methods: This retrospective study included patients with 1 or more potentially allergic symptoms or signs within 4 hours of receiving dose 1 of an mRNA COVID-19 vaccine and assessed by allergy/immunology specialists from 5 U.S. 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. Results: We identified 265 patients with dose-1 immediate reactions with 3 phenotype clusters: (1) Limited or 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. Conclusions: Three novel clinical phenotypes of immediate-onset reactions after dose 1 of mRNA COVID-19 vaccines were identified using latent class analysis: (1) Limited or Predominantly Cutaneous, (2) Sensory, and (3) Systemic. Whereas these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it.",
keywords = "Adverse reaction, Allergy, Anaphylaxis, Cluster, COVID-19, Hypersensitivity, mRNA, Phenotype, SARS-CoV-2, Vaccine",
author = "Stone, {Cosby A.} and Robinson, {Lacey B.} and Lily Li and Krantz, {Matthew S.} and Kwah, {Jason H.} and Gilbert Ortega and Christian Mancini and Wolfson, {Anna R.} and Saff, {Rebecca R.} and Upeka Samarakoon and Hong, {David I.} and Grace Koo and Timothy Chow and Rebecca Gruchalla and Liao, {Jane X.} and Kuster, {John K.} and Christina Price and Catherine Ahola and Khan, {David A} and Phillips, {Elizabeth J.} and Aleena Banerji and Blumenthal, {Kimberly G.}",
note = "Funding Information: This work was supported by the National Institutes of Health (NIH) K01 AI125631 (K. G. Blumenthal); the Agency for Healthcare Research and Quality (AHRQ)/Patient-Centered Outcomes Research Institute (PCORI) 1K12HS026395-01 (C. A. Stone), and the American Academy of Allergy, Asthma, and Immunology (AAAAI) Foundation (C. A. Stone); Massachusetts General Hospital (MGH) DOM Transformative Scholar Program (K. G. Blumenthal); and MGH ECOR Population Health Sciences Award (L. B. Robinson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, AHRQ, AAAAI Foundation, nor MGH.Conflicts of interest: L. B. Robinson reports a speaking honorarium from Viatris as well as employment at both MGH and Sanofi. E. J. Phillips reports personal consulting fees from Janssen, Biocryst, Regeneron, Vertex, AstraZeneca, Verve and UpToDate; royalties from UpToDate; and grants from NIH (R01HG010863, R01AI152183, U01AI154659, R13AR078623, UAI109565) and from the National Health and Medical Research Council of Australia; is codirector of IIID Pty Ltd that holds a patent for HLA-B∗57:01 testing for abacavir hypersensitivity; and has a patent pending for Detection of Human Leukocyte Antigen-A∗32:01 in connection with Diagnosing Drug Reaction with Eosinophilia and Systemic Symptoms without any financial remuneration and not directly related to the submitted work. K. G. Blumenthal reports personal fees from Weekley, Schulte, Valdes, Murman, Tonelli, Vasios, Kelly, Stroll, P. A. and Piedmont Liability Trust; and royalties from UpToDate, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: This work was supported by the National Institutes of Health (NIH) K01 AI125631 (K. G. Blumenthal); the Agency for Healthcare Research and Quality (AHRQ)/Patient-Centered Outcomes Research Institute (PCORI) 1K12HS026395-01 (C. A. Stone), and the American Academy of Allergy, Asthma, and Immunology (AAAAI) Foundation (C. A. Stone); Massachusetts General Hospital (MGH) DOM Transformative Scholar Program (K. G. Blumenthal); and MGH ECOR Population Health Sciences Award (L. B. Robinson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, AHRQ, AAAAI Foundation, nor MGH. Publisher Copyright: {\textcopyright} 2022 American Academy of Allergy, Asthma & Immunology",
year = "2022",
doi = "10.1016/j.jaip.2022.08.048",
language = "English (US)",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
publisher = "Elsevier",
}