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Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients.
Hadjadj, Jérôme; Yatim, Nader; Barnabei, Laura; Corneau, Aurélien; Boussier, Jeremy; Smith, Nikaïa; Péré, Hélène; Charbit, Bruno; Bondet, Vincent; Chenevier-Gobeaux, Camille; Breillat, Paul; Carlier, Nicolas; Gauzit, Rémy; Morbieu, Caroline; Pène, Frédéric; Marin, Nathalie; Roche, Nicolas; Szwebel, Tali-Anne; Merkling, Sarah H; Treluyer, Jean-Marc; Veyer, David; Mouthon, Luc; Blanc, Catherine; Tharaux, Pierre-Louis; Rozenberg, Flore; Fischer, Alain; Duffy, Darragh; Rieux-Laucat, Frédéric; Kernéis, Solen; Terrier, Benjamin.
  • Hadjadj J; Université de Paris, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, F-75015 Paris, France.
  • Yatim N; Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.
  • Barnabei L; Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.
  • Corneau A; Institut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, France.
  • Boussier J; Université de Paris, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, F-75015 Paris, France.
  • Smith N; Sorbonne Université, UMS037, PASS, Plateforme de cytométrie de la Pitié-Salpêtrière CyPS, F-75013 Paris, France.
  • Péré H; Institut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, France.
  • Charbit B; Institut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, France.
  • Bondet V; Université de Paris, INSERM, U970, PARCC, F-75015 Paris, France.
  • Chenevier-Gobeaux C; Service de Microbiologie, AP-HP, APHP-CUP, Hôpital Européen Georges Pompidou, F-75015 Paris, France.
  • Breillat P; Institut Pasteur, Cytometry and Biomarkers UTechS, CRT, F-75015 Paris, France.
  • Carlier N; Institut Pasteur, Laboratory of Dendritic Cell Immunobiology, INSERM U1223, Department of Immunology, F-75015 Paris, France.
  • Gauzit R; Department of Automated Diagnostic Biology, Hôpital Cochin, APHP, APHP-CUP, F-75014 Paris, France.
  • Morbieu C; Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.
  • Pène F; Department of Pulmonology, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, France.
  • Marin N; Equipe Mobile d'Infectiologie, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, France.
  • Roche N; Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.
  • Szwebel TA; Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, F-75006 Paris, France.
  • Merkling SH; Service de Médecine Intensive et Réanimation, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, France.
  • Treluyer JM; Service de Médecine Intensive et Réanimation, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, France.
  • Veyer D; Department of Pulmonology, Hôpital Cochin, AP-HP, APHP-CUP, F-75014 Paris, France.
  • Mouthon L; Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, F-75006 Paris, France.
  • Blanc C; Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.
  • Tharaux PL; Institut Pasteur, Insect-Virus Interactions Unit, UMR 2000, CNRS, Paris, France.
  • Rozenberg F; Université de Paris, Pharmacologie et Evaluation des Thérapeutiques Chez l'Enfant et la Femme Enceinte EA7323, F-75006 Paris, France.
  • Fischer A; Recherche Clinique et Pharmacologie, AP-HP, APHP-CUP, Hôpitaux Cochin Necker, F-75014 Paris, France.
  • Duffy D; Service de Microbiologie, AP-HP, APHP-CUP, Hôpital Européen Georges Pompidou, F-75015 Paris, France.
  • Rieux-Laucat F; Université de Paris and Sorbonne Université, INSERM, Centre de Recherche des Cordeliers, Functional Genomics of Solid Tumors (FunGeST), F-75006 Paris, France.
  • Kernéis S; Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, F-75014 Paris, France.
  • Terrier B; Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, F-75006 Paris, France.
Science ; 369(6504): 718-724, 2020 08 07.
Article in English | MEDLINE | ID: covidwho-641396
ABSTRACT
Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-ß and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Interferon-beta / Interferon-alpha / Coronavirus Infections / Betacoronavirus / Interferon alpha-2 Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abc6027

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Interferon-beta / Interferon-alpha / Coronavirus Infections / Betacoronavirus / Interferon alpha-2 Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abc6027