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Dorgham, K.* ; Quentric, P.* ; Gökkaya, M. ; Marot, S.* ; Parizot, C.* ; Sauce, D.* ; Guihot, A.* ; Luyt, C.E.* ; Schmidt, M.* ; Mayaux, J.* ; Beurton, A.* ; Le Guennec, L.* ; Demeret, S.* ; Ben Salah, E.* ; Mathian, A.* ; Yssel, H.* ; Combadiere, B.* ; Combadière, C.* ; Traidl-Hoffmann, C. ; Burrel, S.* ; Marcelin, A.G.* ; Amoura, Z.* ; Voiriot, G.* ; Neumann, A.U. ; Gorochov, G.*

Distinct cytokine profiles associated with COVID-19 severity and mortality.

J. Allergy Clin. Immunol. 147, 2098-2107 (2021)
Postprint DOI PMC
Open Access Green
BACKGROUND: Markedly elevated levels of pro-inflammatory cytokines and defective type-I interferon responses were reported in COVID-19 patients. OBJECTIVE: This study aimed to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. METHODS: Cytokine concentrations and SARS-CoV-2 antigen were measured at hospital admission in serum of symptomatic COVID-19 patients (N=115), classified at hospitalization into three respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS) and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N=86). RESULTS: At time of hospitalization, ECMO patients presented a dominant pro-inflammatory response with elevated levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at one month was associated with higher levels of pro-inflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (Risk Ratio 24.3, p<0.0001). SARS-CoV-2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with pro-inflammatory response or severity. CONCLUSION: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Covid-19 ; Mortality ; Principal Component Analysis ; Respiratory Severity ; Serum Cytokines ; Type-i Ifns
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Quellenangaben Volume: 147, Issue: 6, Pages: 2098-2107 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Environmental Medicine (IEM)