Type I Interferon Deficiency in Blood Could Be Hallmark of Severe COVID-19, Finds Study

Although most patients experience mild-to-moderate disease, 5-10% progress to severe or critical disease, including pneumonia and acute respiratory distress syndrome (ARDS). Researchers have tried to uncover the cause of the difference between mild disease versus severe and focus on the role of the immune modular IFN. However, little is known about the immunological features and the molecular mechanisms involved in COVID-19 severity.

To test the hypothesis of a virally-driven hyperinflammation leading to severe disease, a group of researchers employed an integrative approach based on clinical and biological data, in-depth phenotypical analysis of immune cells, standardized whole-blood transcriptomic analysis and cytokine measurements on a group of 50 COVID-19 patients with variable severity from mild to critical. This integrated immune analysis revealed a unique phenotype in severe and critical patients, consisting of a highly impaired IFN type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling.

Based on their study, the researchers have proposed that type I IFN deficiency is a hallmark of severe COVID-19 and concluded that severe COVID-19 patients might be potentially relieved from the IFN deficiency by IFN administration and from exacerbated inflammation by adapted anti-inflammatory therapies targeting IL-6 or TNF-α.