Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
Jérôme Hadjadj # 1 2 , Nader Yatim # 2 3 , Laura Barnabei 1 , 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 2 , Nicolas Carlier 9 , Rémy Gauzit 10 , Caroline Morbieu 2 , Frédéric Pène 11 12 , Nathalie Marin 12 , Nicolas Roche 9 11 , Tali-Anne Szwebel 2 , Sarah H Merkling 13 , Jean-Marc Treluyer 14 15 , David Veyer 6 16 , Luc Mouthon 2 11 , Catherine Blanc 4 , Pierre-Louis Tharaux 5 , Flore Rozenberg 11 17 , Alain Fischer 1 18 19 , Darragh Duffy # 3 7 , Frédéric Rieux-Laucat # 1 , Solen Kernéis # 10 20 21 , Benjamin Terrier # 22 5
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-β 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.