In silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions

Abstract

COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. Patients infected with SARS-CoV-2 exhibit heterogeneous symptoms that pose pragmatic hurdles for implementing appropriate therapy and management of the COVID-19 patients and their post-COVID complications. Thus, understanding the impact of infection severity at the molecular level in the host is vital to understand the host response and accordingly it's precise management. In the current study, we performed a comparative transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis employing Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1224 significantly upregulated genes (logFC≥ 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC≤ −1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) revealed the upregulation of anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc.; while, downregulation of lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. Conclusively, these findings provide insight into the enhanced susceptibility of severe COVID-19 patients to other health comorbidities including non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. owing to the activation of biological processes, pathways and molecular functions associated with them. We anticipate this study will facilitate the researchers in finding efficient therapeutic targets and eventually the clinicians in management of COVID-19 patients and post-COVID-19 effects in them.