Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 99, Issue 9, Pages 917-921Publisher
WILEY
DOI: 10.1111/imcb.12495
Keywords
Immunological deficiency syndromes; infectious diseases; innate immunity; translational immunology; viral infection
Categories
Funding
- Division of Intramural Research of the NIAID, NIH
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health (NIH) [R01AI088364]
- National Center for Advancing Translational Sciences (NCATS)
- NIH Clinical and Translational Science Award (CTSA) program [UL1 TR001866]
- Mercatus Center at George Mason University - National Human Genome Research Institute (NHGRI) [UM1HG006504, U24HG008956]
- French National Research Agency (ANR) under the Investments for the Future program - the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-IAHU-01, ANR-10-LABX-62-IBEID]
- French Foundation for Medical Research (FRM) [EQU201903007798]
- ANR GENCOVID project
- Square Foundation, Grandir - Fonds de solidarite pour l'enfance
- SCOR Corporate Foundation for Science, Institut National de la Sante et de la Recherche Medicale (INSERM)
- University of Paris
- ASST Spedali Civili di Brescia
- Regione Lombardia, Italy
- MD-PhD program of the Imagine Institute
- (Fondation Bettencourt-Schueller)
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This study compared clinical outcomes between patients with neutralizing type-I interferon autoantibodies (AAbs) and those without AAbs during hospitalization for COVID-19, revealing that patients with AAbs were more likely to be admitted to the intensive care unit with delayed viral clearance, although their survival was not adversely affected.
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.
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