Distinct cytokine profiles associated with COVID-19 severity and mortality - 03/06/21
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Abstract |
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.
El texto completo de este artículo está disponible en PDF.Graphical abstract |
Key words : COVID-19, serum cytokines, type-I interferons, respiratory severity, mortality, principal-component analysis
Abbreviations used : COVID-19, fCC, ECMO, MVS, PCA, SAPS-II, SARS-CoV-2
Esquema
| This study was supported by the Fondation de France, “Tous unis contre le virus” framework Alliance (Fondation de France, AP-HP, Institut Pasteur) in collaboration with Agence Nationale de la Recherche (ANR Flash COVID19 program), by the SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs, by the Programme Hospitalier de Recherche Clinique PHRC-20-0375 COVID-19 (PI: G.G.), by the Christine Kühne - Center for Allergy Research and Education (M.G., C.T.-H., and A.U.N.), and by the Initiative and Networking Fund (Immunology & Inflammation) of the Helmholtz Association (M.G., C.T.-H., and A.U.N.). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 6
P. 2098-2107 - juin 2021 Regresar al número
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