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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, * 
* Corresponding author
1 Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière]
DMIIC - Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière]
2 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
4 PASS-CYPS - Cytométrie Pitié-Salpêtrière
PASS - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé
Abstract : 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.
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Impaired type I interferon act...
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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, American Association for the Advancement of Science (AAAS), 2020, Online ahead of print, pp.eabc6027. ⟨10.1126/science.abc6027⟩. ⟨pasteur-02900830⟩



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