Association of Varying Clinical Manifestations and Positive Anti–SARS-CoV-2 IgG Antibodies: A Cross-Sectional Observational Study

Jonathan I. Silverberg, Israel Zyskind, Hiam Naiditch, Jason Zimmerman, Aaron E. Glatt, Abraham Pinter, Elitza S. Theel, Michael J. Joyner, D. Ashley Hill, Miriam R. Lieberman, Elliot Bigajer, Daniel Stok, Elliot Frank, Avi Z. Rosenberg

Research output: Contribution to journalArticlepeer-review


Background: The complex relationship between clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and individual immune responses is not fully elucidated. Objective: To examine phenotypes of symptomatology and their relationship with positive anti–SARS-CoV-2 IgG antibody responses. Methods: An observational study was performed of adults (≥18 years) from 5 US states. Participants completed an electronic survey and underwent testing to anti–SARS-CoV-2 nucleocapsid protein IgG antibody between May and July 2020. Latent class analysis was used to identify characteristic symptom clusters. Results: Overall, 9507 adults (mean age, 39.6 ± 15.0 years) completed the survey; 6665 (70.1%) underwent antibody testing for anti–SARS-CoV-2 IgG. Positive SARS-CoV-2 antibodies were associated with self-reported positive SARS-CoV-2 nasal swab result (bivariable logistic regression; odds ratio [95% CI], 5.98 [4.83-7.41]), household with 6 or more members (1.27 [1.14-1.41]) and sick contact (3.65 [3.19-4.17]), and older age (50-69 years: 1.55 [1.37-1.76]; ≥70 years: 1.52 [1.16-1.99]), but inversely associated with female sex (0.61 [0.55-0.68]). Latent class analysis revealed 8 latent classes of symptoms. Latent classes 1 (all symptoms) and 4 (fever, cough, muscle ache, anosmia, dysgeusia, and headache) were associated with the highest proportion (62.0% and 57.4%) of positive antibodies, whereas classes 6 (fever, cough, muscle ache, headache) and 8 (anosmia, dysgeusia) had intermediate proportions (48.2% and 40.5%), and classes 3 (headache, diarrhea, stomach pain) and 7 (no symptoms) had the lowest proportion (7.8% and 8.5%) of positive antibodies. Conclusions: SARS-CoV-2 infections manifest with substantial diversity of symptoms, which are associated with variable anti–SARS-CoV-2 IgG antibody responses. Prolonged fever, anosmia, and receiving supplemental oxygen therapy had strongest associations with positive SARS-CoV-2 IgG.

Original languageEnglish (US)
Pages (from-to)3331-3338.e2
JournalJournal of Allergy and Clinical Immunology: In Practice
Issue number9
StatePublished - Sep 2021


  • Convalescent
  • Infection
  • Phenotype
  • Seroprevalence
  • Symptoms

ASJC Scopus subject areas

  • Immunology and Allergy


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