The Journal of Allergy and Clinical Immunology | June 1, 2021

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

The Journal of allergy and clinical immunology. 2021

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.

Graphical abstract