Bioinformatics and system biology approach to identify the influences of COVID-19 on cardiovascular and hypertensive comorbidities

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-$19$ and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-$2$ infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-$2$ uses the angiotensin converting enzyme-$2$ (ACE-$2$) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin–angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-$2$, although there are claims that such medications actually reduce lung injury caused by COVID-$19$. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-$19$ patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-$19$ to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-$19$ and chronic heart failure, and common to COVID-$19$ and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-$19$ does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein–protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-$2$ infection.

Sex-Related Overactivation of NLRP3 Inflammasome Increases Lethality of the Male COVID-19 Patients

“…During SARS-CoV-2 infection, testosterone level may be elevated because ACE-2 is expressed by Leydig cell and can be hijacked by the virus (Nashiry et al, 2021), which in turn leads to inflammatory pyroptosis in Leydig cells and increased extracellular ATP levels (Zhang et al, 2017). These extracellular ATPs activate P2X receptors expressed in Leydig cells (Antonio et al, 2009) and promote testosterone secretion (Foresta et al, 1996).…”

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

“…The first symptoms of COVID-19 resemble those of many other infections and inflammatory conditions that affect the respiratory system; they include fever, sneezing and rhinitis, persistent cough, and fatigue with body ache [2]. 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].…”

Bioinformatics and system biology approaches to identify the diseasome and comorbidities complexities of SARS-CoV-2 infection with the digestive tract disorders

“…In SARS-CoV-2 patients, this might be functioning as a negative regulator of the T-cell activation so that there is a considerable balance between the activation and overactivation after infection. Recent studies show that the presence of GNLY can also be observed with COVID-19 patients having heart disease [ 31 ]. GNLY functions as a chemoattractant for T cells, monocytes and other inflammatory cells and stimulates several other cytokines and also helps in the recruitment of immune cells to the infection site as observed in SARS-CoV-2 infection.…”

“…We have discovered several significant miRNAs in the interaction between Crohn’s and COVID-19 such as hsa-mir-1-3p, hsa-mir-124-3p, hsa-mir-129-2-3p. Studies have shown that miR-1-3p is known to be involved in heart diseases [ 31 ] and also plays significant roles in the development of human cancers such as lung cancer, bladder cancer or prostate cancer [ 77 ]. These two mi-RNAs are also available in the network of ulcerative colitis and COVID-19.…”

“…Bioinformatics and system biology approaches are common to identify and analyze the comorbidity complexities [ 31–37 ]. Datasets required in this work have been identified and collected at the initial phase, which is detailed in the following subsection.…”