Alterations in the interferon pathway within Covid-19 infection

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that emerged in late 2019 in Wuhan, China. Although much attention has been placed in virus host cell receptors, little has been described about the anti-viral proteins. It is well accepted that type I interferon (IFN) is essential in fighting viral infection by induction of IFN-stimulated genes (ISGs), which work in synergy to inhibit viral replication via multiple mechanisms. In this work, we aimed at evaluating the expression profiles of several genes associated with the IFN pathway in response to the infection with SARS-CoV-2 in COVID-19 positive patients vs. COVID-19 negative patients. We performed bioinformatics analyses in a case-control study from SARS-CoV-2 positive (n=403) and negative (n=54) patients. Samples were obtained from nasopharyngeal swabs. We analyzed the differential expression of the IFN-associated genes alongside with their correlation with other clinical parameters such as age, sex and viral load. Results show a significant downregulation of IFGNR1, STAT6, JUN, MAP3K1, CEBPB, and RAPGEF1 in COVID-19 positive patients. We also found a significant correlation between most of the genes and the viral load. No significant differences were observed between gene expression and age or sex. In summary, our study findings support the role of IFN and IFN-associated genes in SARS-CoV-2 infection, pointing out to new potential drugable targets in order to achieve a better anti-viral response.