Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 42, Issue 3, Pages 459-470Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-021-01203-3
Keywords
Autoantibodies; type I interferons; COVID-19; mortality
Categories
Funding
- 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]
- Fast Grant from Emergent Ventures
- Mercatus Center at George Mason University
- Yale Center for Mendelian Genomics
- GSP Coordinating Center - National Human Genome Research Institute (NHGRI) [UM1HG006504, U24HG008956]
- Yale High Performance Computing Center [S10OD018521]
- Fisher Center for Alzheimer's Research Foundation
- Meyer Foundation
- JPB Foundation
- French National Research Agency (ANR) under the Investments for the Future program [ANR-10-IAHU-01]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- French Foundation for Medical Research (FRM) [EQU201903007798, EA20170638020]
- ANR GENCOVID project [ANR-20-COVI-0003]
- ANRS Nord-Sud [ANRS-COV05]
- ANR GENVIR [ANR-20-CE93-003]
- ANR AABIFNCOV [ANR-20-CO11-0001]
- European Union's Horizon 2020 research and innovation program [824110]
- Square Foundation
- Grandir-Fonds de solidarite pour l'enfance
- Fondation du Souffle
- SCOR Corporate Foundation for Science
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- University of Paris
- MD-PhD program of the Imagine Institute (Fondation Bettencourt-Schueller)
- Agence Nationale de la Recherche (ANR) [ANR-20-COVI-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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Recent studies have found that pre-existing autoantibodies neutralizing type I interferons (IFNs) are present in at least 15% of patients with critical COVID-19 pneumonia, increasing the risk of mortality. This highlights the importance of type I IFN immunity in defense against SARS-CoV-2 infection and the usefulness of detecting autoantibodies for patient management.
Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of deceased patients across all ages. We aimed to assess the prevalence and clinical impact of the auto-Abs to type I IFNs in the Seine-Saint-Denis district, which was one of the most affected areas by COVID-19 in France during the first wave. We tested for the presence of auto-Abs neutralizing type I IFNs in a cohort of patients admitted for critical COVID-19 pneumonia during the first wave in the spring of 2020 in the medicine departments at Robert Ballanger Hospital, Aulnay sous Bois. We found circulating auto-Abs that neutralized 100 pg/mL IFN-alpha 2 and/or IFN-omega in the plasma (diluted 1/10) of 7.9% (11 of 139) of the patients hospitalized for critical COVID-19. The presence of neutralizing auto-Abs was associated with an increased risk of mortality, as these auto-Abs were detected in 21% of patients who died from COVID-19 pneumonia. Deceased patients with and without auto-Abs did not present overt clinical differences. These results confirm both the importance of type I IFN immunity in host defense against SARS-CoV-2 infection and the usefulness of detection of auto-Abs neutralizing type I IFNs in the management of patients.
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