Identification of biomarkers and pathways for the SARS-CoV-2 infections that make complexities in pulmonary arterial hypertension patients

Abstract

This study aimed to identify significant gene expression profiles of the human lung epithelial cells caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We performed a comparative genomic analysis to show genomic observations between SARS-CoV and SARS-CoV-2. A phylogenetic tree has been carried for genomic analysis that confirmed the genomic variance between SARS-CoV and SARS-CoV-2. Transcriptomic analyses have been performed for SARS-CoV-2 infection responses and pulmonary arterial hypertension (PAH) patients’ lungs as a number of patients have been identified who faced PAH after being diagnosed with coronavirus disease 2019 (COVID-19). Gene expression profiling showed significant expression levels for SARS-CoV-2 infection responses to human lung epithelial cells and PAH lungs as well. Differentially expressed genes identification and integration showed concordant genes (SAA2, S100A9, S100A8, SAA1, S100A12 and EDN1) for both SARS-CoV-2 and PAH samples, including S100A9 and S100A8 genes that showed significant interaction in the protein–protein interactions network. Extensive analyses of gene ontology and signaling pathways identification provided evidence of inflammatory responses regarding SARS-CoV-2 infections. The altered signaling and ontology pathways that have emerged from this research may influence the development of effective drugs, especially for the people with preexisting conditions. Identification of regulatory biomolecules revealed the presence of active promoter gene of SARS-CoV-2 in Transferrin-micro Ribonucleic acid (TF-miRNA) co-regulatory network. Predictive drug analyses provided concordant drug compounds that are associated with SARS-CoV-2 infection responses and PAH lung samples, and these compounds showed significant immune response against the RNA viruses like SARS-CoV-2, which is beneficial in therapeutic development in the COVID-19 pandemic.

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

“…Panx-1 channels participate in several inflammatory conditions exacerbated during COVID-19 pathogenesis, including hypoxia, coagulation, blood pressure, endothelial permeability, and apoptosis (Abdeen et al, 2021;AbdelMassih et al, 2021;Chang et al, 2020;Contoli et al, 2021;Hertzog et al, 2021;Li et al, 2020;Liu et al, 2020b;Montero et al, 2020;Page et al, 2021;Taz et al, 2021;Toldo et al, 2021;Wang et al, 2020). We propose that upon Panx-1 channel opening, several biomolecules are released into the extracellular space and result in modulation of COVID-19 pathogenesis: first, ATP release and modification of local signaling enable viral entry through the activation of purinergic receptors; second, IL-1b release results in a pro-inflammatory response and recruitment of leukocytes into the area of infection (Kim et al, 2015); and third, the release of PGE 2 into the extracellular matrix and its role in coagulation/ vascular compromise (Friedman et al, 2015;Gross et al, 2007) highlight its importance in extensively vascularized regions that become damaged when challenged by conditions such as SARS-CoV-2 infection.…”

Machine Learning Approach to Predicting COVID-19 Disease Severity Based on Clinical Blood Test Data: Statistical Analysis and Model Development

“…However, an infected patient can rapidly develop additional and more severe symptoms that can be life-threatening and require intensive care intervention; these include pneumonia, severe shortness of breath, diarrhea, dispersed thrombosis, and vascular inflammation [3,4]. An additional issue in caring for patients with COVID-19 is the presence of comorbidities that interact with COVID-19, particularly pulmonary and vascular conditions, which can greatly worsen the patient's prognosis [5]. This is an important consideration given the current lack of effective therapy for COVID-19.…”

Covid-19 and development of heart failure: mystery and truth

“…In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF (Belhadjer et al 2020 ). Hypoxic respiratory failure, as in pulmonary edema, severe ALI, and ARDS may affect heart hemodynamic stability due to the development of pulmonary hypertension (Taz et al 2021 ). Indeed, Covid-19-induced HF might be through the development of cytokine storm, which is characterized by high pro-inflammatory cytokines such as IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) that lead to fulminant myocarditis (Chen et al 2020a ).…”