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

Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France. Department of Environmental Medicine, Faculty of Medicine, University Hospital of Augsburg, Augsburg, Germany; Institute of Environmental Medicine (IEM), Technical University of Munich and Helmholtz Zentrum München, Augsburg, Germany. Sorbonne Université, Inserm, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département de Virologie, Paris, France. Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France. AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Intensive Réanimation, Institut de Cardiologie, Paris, France; Sorbonne Université, Inserm, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France. AP-HP, Hôpital Pitié-Salpêtrière, Service de Pneumologie, Médecine Intensive - Réanimation, Paris, France. AP-HP, Hôpital Pitié-Salpêtrière, Service de Pneumologie, Médecine Intensive - Réanimation, Paris, France; Sorbonne Université, Inserm UMR S 1158, Neurophysiologie respiratoire expérimentale et clinique, Paris, France. Sorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive et Réanimation Neurologique, Paris, France. Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Interne 2, Institut E3M, Paris, France. Department of Environmental Medicine, Faculty of Medicine, University Hospital of Augsburg, Augsburg, Germany; Institute of Environmental Medicine (IEM), Technical University of Munich and Helmholtz Zentrum München, Augsburg, Germany; Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. AP-HP, Hôpital Tenon, Service de Médecine Intensive Réanimation, Paris, France. Department of Environmental Medicine, Faculty of Medicine, University Hospital of Augsburg, Augsburg, Germany; Institute of Environmental Medicine (IEM), Technical University of Munich and Helmholtz Zentrum München, Augsburg, Germany; Institute of Experimental Medicine (IEM), Czech Academy of Sciences, Prague, Czech Republic. Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France. Electronic address: guy.gorochov@sorbonne-universite.fr.

The Journal of allergy and clinical immunology. 2021;(6):2098-2107
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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.

Methodological quality

Publication Type : Clinical Trial

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MeSH terms : Cytokines ; SARS-CoV-2