Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients.
Jérôme HadjadjNader YatimLaura BarnabeiAurélien CorneauJeremy BoussierNikaïa SmithHélène PéréBruno CharbitVincent BondetCamille Chenevier-GobeauxPaul BreillatNicolas CarlierRémy GauzitCaroline MorbieuFrédéric PèneNathalie MarinNicholas RocheTali-Anne SzwebelSarah Hélène MerklingJean-Marc TreluyerDavid VeyerLuc MouthonCatherine BlancPierre-Louis TharauxFlore RozenbergAlain FischerDarragh DuffyFrédéric Rieux-LaucatSolen KerneisBenjamin TerrierPublished in: Science (New York, N.Y.) (2020)
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.
Keyphrases
- coronavirus disease
- dendritic cells
- immune response
- sars cov
- nuclear factor
- toll like receptor
- inflammatory response
- early onset
- respiratory syndrome coronavirus
- end stage renal disease
- newly diagnosed
- oxidative stress
- peritoneal dialysis
- rheumatoid arthritis
- clinical trial
- electronic health record
- lipopolysaccharide induced
- prognostic factors
- drug induced
- big data
- replacement therapy