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Distinct cytokine profiles associated with COVID-19 severity and mortality.
Dorgham, Karim PhD a,*; Quentric, Paul MD, MSc a,*; Gokkaya, Mehmet MSc b,c,*; Marot, Stephane MD d; Parizot, Christophe MSc a,e; Sauce, Delphine PhD a; Guihot, Amelie MD, PhD a,e; Luyt, Charles-Edouard MD, PhD f,g; Schmidt, Matthieu MD, PhD f,g; Mayaux, Julien MD h; Beurton, Alexandra MD, PhD h,i; Le Guennec, Loic MD, PhD j; Demeret, Sophie MD j; Salah, Elyes Ben PharmD, MSc a,e; Mathian, Alexis MD, PhD a,k; Yssel, Hans PhD a; Combadiere, Behazine PhD a; Combadiere, Christophe PhD a; Traidl-Hoffmann, Claudia MD, PhD b,c,l; Burrel, Sonia PharmD, PhD d; Marcelin, Anne-Genevieve PharmD, PhD d; Amoura, Zahir MD, PhD a,k; Voiriot, Guillaume MD m; Neumann, Avidan U. PhD b,c,n,++; Gorochov, Guy MD, PhD a,e,*,++
[Miscellaneous Article] Journal of Allergy & Clinical Immunology. 147(6):2098-2107, June 2021.

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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-[alpha], IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-[alpha] and IFN-[beta] 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.