Distinct cytokine profiles associated with COVID-19 severity and mortality

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Dorgham, Karim | Quentric, Paul | Gökkaya, Mehmet | Marot, Stéphane | Parizot, Christophe | Sauce, Delphine | Guihot, Amélie | Luyt, Charles-Edouard | Schmidt, Matthieu | Mayaux, Julien | Beurton, Alexandra | Le Guennec, Loic | Demeret, Sophie | Ben Salah, Elyes | Mathian, Alexis | Yssel, Hans | Combadiere, Béhazine | Combadiere, Christophe | Traidl-Hoffmann, Claudia | Burrel, Sonia | Marcelin, Anne-Geneviève | Amoura, Zahir | Voiriot, Guillaume | Neumann, Avidan, U | Gorochov, Guy

Edité par CCSD ; Elsevier -

International audience. Background: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19).Objective: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality.Methods: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 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 proinflammatory response with elevated levels of TNF-α, 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 1 month was associated with higher levels of proinflammatory 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 < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity.Conclusions: 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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