Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science
    • Subject Terms:
      COVID-19*/immunology ; COVID-19*/virology ; Autoantibodies*/immunology ; Autoantibodies*/blood ; SARS-CoV-2*/immunology ; Interferon-alpha*/immunology; Humans ; Male ; Female ; Adult ; Middle Aged ; Immunoglobulin A/immunology ; Immunoglobulin A/blood ; Immunoglobulin G/immunology ; Immunoglobulin G/blood ; Respiratory System/immunology ; Respiratory System/virology
    • Abstract:
      Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.
    • Grant Information:
      P01 AI125180 United States AI NIAID NIH HHS; R01 AI121252 United States AI NIAID NIH HHS; R01 AI123126 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Autoantibodies)
      0 (Interferon-alpha)
      0 (Immunoglobulin A)
      0 (Immunoglobulin G)
    • Publication Date:
      Date Created: 20241106 Date Completed: 20241106 Latest Revision: 20241210
    • Publication Date:
      20241210
    • Accession Number:
      10.1126/scitranslmed.adq1789
    • Accession Number:
      39504354