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 in ammation 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 signi cantly 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 signi cantly 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 in ammatory 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 in ammatory and oxidative stress strom in severe COVID-19 patietnts.

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

“…Increased soluble RAGE in serum is also a predictor of mortality among COVID−19 patients ( 31 , 32 ). The expression of RAGE was significantly increased in patients with severe COVID-19, along with its ligands, including S100 and HMGB-1 ( 263 , 264 ), and a system-wide transcriptomic analysis identified RAGE among the strongly upregulated genes in the liver, and among the slightly, but significantly upregulated genes in the heart and lymph nodes of COVID-19 patients (Supplementary Table S2 to ( 265 )). The causal involvement of RAGE in vascular injury and severe disease in COVID-19 patients was underlined by the reduced systemic inflammation and damage to blood vessels and increased survival of mice treated with pharmacological inhibitors of RAGE ( 262 ).…”

COVID-19 and Kidney: The Importance of Follow-Up and Long-Term Screening

“…The alteration of TRPC6 might potentiate SARS-CoV-2-induced inflammation in patients infected with SARS-CoV-2 [20]. Further, the receptor for advanced glycation end-product (RAGE) expression is enhanced in COVID-19 and is associated with its severity and patients' morbidity and mortality [21]. In podocytes, increased RAGE activates TRPC6 through activated Src kinases, and activated TRPC6 is related to podocyte injury [22].…”