Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19 .
Objective: To evaluate the interferon (IFN) -α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile .
Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls . After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days . The severity of the clinical condition was ranked based on the level of respiratory support required . At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay .
Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled . At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p <0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels . A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects . Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died . In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels . Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention . Clinical Trial Registration: ClinicalTrials.gov identifier NCT04343053.
Index: COVID−19, SARS–CoV−2, interferon, mortality, respiratory failure