Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-34895-1
Keywords
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Categories
Funding
- Institut Pasteur
- Agence Nationale de la Recherche
- Laboratoire d'Excellence `Milieu Interieur' [ANR-10-LABX69-01]
- Fonds IMMUNOV for Innovation in Immunopathology
- Science Foundation Ireland
- Pasteur-Roux-Cantarini Fellowship
- Science Foundation Ireland (SFI) [20/SPP/3685]
- Irish Clinical Academic Training (ICAT) Program
- Wellcome Trust
- Health Research Board [203930/B/16/Z]
- Health Service Executive, National Doctors Training and Planning
- Health and Social Care, Research and Development Division, Northern Ireland
- Science Foundation Ireland Phase 2 COVID-19 Rapid Response Call [20/COV/8487]
- Health Research Board COVID-19 Rapid Response Call [COV19e2020e053]
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health (NIH) [R01AI088364, R01AI163029]
- National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program [UL1 TR001866]
- Emergent Ventures
- Mercatus Center at George Mason University
- Fisher Center for Alzheimer's Research Foundation
- Meyer Foundation
- JPB Foundation
- French National Research Agency (ANR) [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]
- ANR GENVIR project [ANR-20-CE93-003]
- ANR AABIFNCOV project [ANR-20-CO11-0001]
- ANR GenMISC project [ANR-21-COVR-0039]
- 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
- French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- REACTing-INSERM
- University of Paris
- Imagine Institute
- Fondation Bettencourt-Schueller
- UTechS CB of the Center for Translational Research, Institut Pasteur
- [ANRS-COV05]
- Agence Nationale de la Recherche (ANR) [ANR-21-COVR-0039] Funding Source: Agence Nationale de la Recherche (ANR)
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The interferon response is linked to the severity of SARS-CoV-2 infection and is a crucial part of the immune response to COVID-19. This study stratifies patients based on COVID-19 severity and assesses the interferon response, revealing defective responses in severe infection. The study also highlights the importance of assay variables and confounding factors that affect interferon detection.
The interferon response has been shown to be linked to severity of SARS-CoV-2 infection and is an essential component of the immune response to COVID-19. Here the authors stratify patients according to COVID-19 severity and asses the interferon response showing defective responses in severe infection and highlight the importance of assay variables and confounding factors that impact the detection of interferon. Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon alpha measures differ according to the immunoassay used, timing of sampling, the interferon alpha subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon alpha or interferon omega. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.
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