Enhanced Expression of RAGE AXIS is Associated with Severity of COVID-19 in Patients with Comorbidities

Abstract

There is a limited understanding of molecular and cellular events that derive disease progression in patients with COVID-19. Receptor for Advanced Glycation End Products (RAGE) is hyperactive in development and complications of several diseases by mediating oxidative stress and inflammation in the body. The present study aims to explore activation of RAGE signaling in patients infected with SARS-CoV-2 with preexisting comorbidities. Enhanced levels of ligands of RAGE including AGEs, S100, and HMGB-1 were observed in Covid 19 patients with severe diseases, however, their level was significantly higher in COVID-19 patients with comorbidties as compared to COVID-19 patients without comorbidties. The Expression of RAGE in parallel to ligands accumulation, was significantly increased in patients with severe disease and comorbidities as compared to COVID-19 patients with sever disease without comorbidities. The expression of downstream effectors of RAGE including STAT-3 and NF-kB were also enahnced and their activity was increaed in COVID-19 patients with comorbisdities. Levels of inflammatory and oxidative stress biomarkers were markeldy in COVID-19 patients with comorbidties as compared to COVID-19 patients without comorbidties. We conclude that upregulated RAGE axis is favorable to worsen the severity of the SARS-CoV-2 infection in patients with preexisting comorbidities and partly explain inflammatory and oxidative stress strom in severe COVID-19 patietnts.