Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Jérôme Hadjadj (1, 2) , Nader Yatim (3, 1) , Laura Barnabei (2) , Aurélien Corneau (4) , Jeremy Boussier (3) , Nikaïa Smith (3) , Hélène Péré (5, 6) , Bruno Charbit (7) , Vincent Bondet (3) , Camille Chenevier-Gobeaux (8) , Paul Breillat (1) , Nicolas Carlier (9, 10) , Rémy Gauzit (11) , Caroline Morbieu (1) , Frédéric Pène (10, 12) , Nathalie Marin (12, 10) , Nicolas Roche (9, 10) , Tali-Anne Szwebel (1) , Sarah Hélène Merkling (13) , Jean-Marc Treluyer (14) , David Veyer (6) , Luc Mouthon (1) , Catherine Blanc (4) , Pierre-Louis Tharaux (5) , Flore Rozenberg (15) , Alain Fischer (2, 16, 17) , Darragh Duffy (3, 7) , Frédéric Rieux-Laucat (2) , Solen Kernéis (11, 18) , Benjamin Terrier (19, 5)

1 Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière]
2 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
3 Immunobiologie des Cellules dendritiques
4 PASS-CYPS - Cytométrie Pitié-Salpêtrière
5 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
6 Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP]
7 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
8 Diagnostic biologique automatisé [AP-HP Cochin]
9 Service de pneumologie [CHU Cochin]
10 IC UM3 (UMR 8104 / U1016) - Institut Cochin
11 Unité Equipe mobile d'Infectiologie [AP-HP Cochin]
12 Unité de Soins Intensifs [CHU Cochin]
13 IVI - Interactions Virus-Insectes - Insect-Virus Interactions
14 CRPV - Centre Régional de Pharmacovigilance
15 Service de Virologie [CHU Cochin]
16 Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP]
17 Collège de France - Chaire Médecine expérimentale (A. Fischer)
18 EMAE - Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials
19 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-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.

Domains: Immunology

Jérôme Hadjadj, Nader Yatim, Laura Barnabei, Aurélien Corneau, Jeremy Boussier, et al.. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science, 2020, Online ahead of print, pp.eabc6027. ⟨10.1126/science.abc6027⟩. ⟨pasteur-02900830⟩