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

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.