ABSTRACT
Background: Markedly elevated levels of pro-inflammatory cytokines and defective type-I interferon responses were reported in COVID-19 patients. This study aimed to determine whether particular profiles of cytokine combinations and SARS-CoV-2 viral loads are associated with COVID-19 severity and mortality. Method: Cytokine concentrations and SARS-CoV-2 antigen were measured at hospital admission in serum of symptomatic COVID-19 patients (N = 115), classified at hospitalization into three respiratory severity groups: moderate severity with 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, moderately severe No-MVS patients presented an elevated type-I interferon response involving IFN-α and IFN-β, with relatively low levels of pro-inflammatory cytokines. In contrast, critically severe ECMO patients presented a dominant pro-inflammatory response and relatively low type-I interferon response. Intermediate severity MVS patients exhibited a mix of the above cytokine combination profiles. SARS-CoV-2 antigen levels correlated with type-I interferon levels, but not with pro-inflammatory response. Mortality at one month after hospitalization was accurately (87%) predicted by higher levels of IFN-α, IFN-β, and Il-10 in combination with higher SARS-CoV-2 antigenemia and older patients' age, irrespectively of the oxygen support modality. Conclusion: Different levels of two distinct cytokine profiles are observed in different patients in association with COVID-19 severity. Furthermore, by measuring three cytokines and SARS-CoV-2 antigen at time of hospital admission, mortality one month later can be accurately predicted. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling and viral load measurement.