Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (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. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.
Our study has some limitations. First, the study was designed as a cross-sectional analysis, although sequential time points were available for some patients. Second, data provided are mainly derived from the blood and do not allow the assessment of immune responses within the lung. In this respect, data from Bost et al. describe a reduced type I IFN signature in BAL macrophages from severe COVID-19 patients, supporting the validity of our analysis (29).
Based on our study, we propose that type I IFN deficiency is a hallmark of severe COVID-19 and infer 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, a hypothesis worth cautious testing.
Reference & Source information : https://science.sciencemag.org/
Read More on: