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Publications

Journal Article Research Support, Non-U.S. Gov't Ppublish 73 citations

PubMed: 34357402 DOI: 10.1084/jem.20211211

Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs.

J Exp Med 218(10)

Authors: Jonathan Lopez, Marine Mommert, William Mouton, Andrés Pizzorno, Karen Brengel-Pesce, Mehdi Mezidi, Marine Villard, Bruno Lina, Jean-Christophe Richard, Jean-Baptiste Fassier, Valérie Cheynet, Blandine Padey, Victoria Duliere, Thomas Julien, Stéphane Paul, Paul Bastard, Alexandre Belot, Antonin Bal, Jean-Laurent Casanova, Manuel Rosa-Calatrava, Florence Morfin, Thierry Walzer, Sophie Trouillet-Assant

Affiliations

  • Molecular biology core facility, Civils Hospices of Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
  • Joint Research Unit Civils Hospices of Lyon-bioMérieux, Civils Hospices of Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
  • Open Innovation & Partnerships, bioMérieux S.A. Marcy l'Etoile, France.
  • International Center of Research in Infectiology, Institut National de la Santé et de la Recherche Médicale U1111, Centre National de la Recherche Scientifique UMR5308, École normale supérieure Lyon, Claude Bernard Lyon 1 University, Lyon, Rhône, France.
  • Intensive Care Medicine, Croix-Rousse hospital, Claude Bernard Lyon 1 University, Lyon, France.
  • Virology laboratory, Institute of Infectious Agents, Laboratory associated with the National Reference Centre for Respiratory Viruses, Civils Hospices of Lyon, Lyon, France.
  • Occupational Health and Medicine Department, Hospices Civils de Lyon, Lyon, France.
  • Université Claude Bernard Lyon 1, Institut français des sciences et technologies des transports, de l'aménagement et des reseaux, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement, UMR T_9405, Lyon University, Lyon, France.
  • Signia Therapeutics SAS, Lyon, France.
  • VirNext, Faculty of Medicine RTH Laennec, Claude Bernard Lyon 1 University, Lyon University, Lyon, France.
  • Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
  • University of Paris, Imagine Institute, Paris, France.
  • St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Howard Hughes Medical Institute, New York, NY.

Abstract

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.

MeSH

Immunity, Infections, Autoantibodies, Mucous Membrane, Sars Virus, Viral Load, Covid-19, Sars-Cov-2

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