Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19

Michael S. Abers, Lindsey B. Rosen, Ottavia M. Delmonte, Elana Shaw, Paul Bastard, Luisa Imberti, Virginia Quaresima, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Jean Laurent Casanova, Helen C. Su, Luigi D. Notarangelo, Steven M. Holland, Michail S. Lionakis

Research output: Contribution to journalArticlepeer-review

Abstract

Type-I interferons (IFNs) mediate antiviral activity and have emerged as important immune mediators during coronavirus disease 19 (COVID-19). Several lines of evidence suggest that impaired type-I IFN signaling may predispose to severe COVID-19. However, the pathophysiologic mechanisms that contribute to illness severity remain unclear. In this study, our goal was to gain insight into how type-I IFNs influence outcomes in patients with COVID-19. To achieve this goal, we compared clinical outcomes between 26 patients with neutralizing type-I IFN autoantibodies (AAbs) and 192 patients without AAbs who were hospitalized for COVID-19 at three Italian hospitals. The presence of circulating AAbs to type-I IFNs was associated with an increased risk of admission to the intensive care unit and a delayed time to viral clearance. However, survival was not adversely affected by the presence of type-I IFN AAbs. Our findings provide further support for the role of type-I IFN AAbs in impairing host antiviral defense and promoting the development of critical COVID-19 pneumonia in severe acute respiratory syndrome coronavirus 2-infected individuals.

Original languageEnglish
JournalImmunology and Cell Biology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Immunological deficiency syndromes
  • infectious diseases
  • innate immunity
  • translational immunology
  • viral infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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