Expansion of Single Cell Transcriptomics Data of SARS-CoV Infection in Human Bronchial Epithelial Cells to COVID-19

Abstract

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19) that was emerged as a new member of coronaviruses since December 2019 in Wuhan, China and then after was spread in all continentals. Since SARS-CoV-2 has shown about 77.5% similarity to SARS-CoV, the transcriptome and immunological regulations of SARS-CoV-2 was expected to have high percentage of overlap with SARS-CoV. Results In this study, we applied the single cell transcriptomics data of human bronchial epithelial cells (2B4 cell line) infected with SARS-CoV, which was annotated in the Expression Atlas database to expand this data to COVID-19. In addition, we employed system biology methods including gene ontology (GO) and Reactome pathway analyses to define functional genes and pathways in the infected cells with SARS-CoV. The transcriptomics analysis on the Expression Atlas database revealed that most genes from infected 2B4 cell line with SARS-CoV were downregulated leading to immune system hyperactivation, induction of signaling pathways, and consequently a cytokine storm. In addition, GO:0016192 (vesicle-mediated transport), GO:0006886 (intracellular protein transport), and GO:0006888 (ER to Golgi vesicle-mediated transport) were shown as top three GOs in the ontology network of infected cells with SARS-CoV. Meanwhile, R-HAS-6807070 (phosphatase and tensin homolog or PTEN regulation) showed the highest association with other Reactome pathways in the network of infected cells with SARS-CoV. PTEN plays a critical role in the activation of dendritic cells, B- and T-cells, and secretion of proinflammatory cytokines, which cooperates with downregulated genes in the promotion of cytokine storm in the COVID-19 patients. Conclusions Based on the high similarity percentage of the transcriptome of SARS-CoV with SARS-CoV-2, the data of immunological regulations, signaling pathways, and proinflammatory cytokines in SARS-CoV infection can be expanded to COVID-19 to have a valid platform for future pharmaceutical and vaccine studies.

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

“…Infected bronchial epithelium in COVID-19 patient was studied to manifest a strong relation of SARS-CoV with SARS-CoV-2 in immunological pathophysiology and pro-inflammatory cytokines which lead to cytokine storm in affected COVID-19 patients [ 33 ]. Endothelial activation in Cytokine Storm Syndrome (CSS) may lead to unstable hemodynamics, capillary leakage, and coagulopathies and increased production of pro-inflammatory cytokines could release von Willebrand factor and angiopoietin-2 that further stimulate the endothelium activation [ 34 ].…”

Angiotensin System Polymorphisms’ in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study

“…Based on the observation of the high similarity of SARS-CoV-2 with SARS-CoV-1, a recent study suggests the hypothesis that also during COVID-19 many genes can be downregulated leading to immune system hyperactivation, induction of signaling pathways and a subsequent cytokine storm. 6 Several studies reported that SARS-CoV-2 is highly selective towards the angiotensin system. 7 In fact, it has been ascertained that the virus binds strictly the ACE2 -expressing cells widely distributed in blood vessels and tissues/organs (lungs, heart, kidney and eye), a condition that explains the SARS-CoV-2 widespreading.…”

Potential therapeutic agents to COVID-19: An update review on antiviral therapy, immunotherapy, and cell therapy

“…The inability of the immune system to control this condition has led to the death of many patients with COVID-19. The immune response features in COVID-19 are similar to the immune response in SARS-CoV and MERS-CoV infections [8] .…”

“…Within this regard, evidence was rapidly reported that the patients are being affected by an infection with a novel betacoronavirus, which was nominated as SARS-CoV-2 [5] , [6] , [7] , which represents a pandemic threat to global public health [7] . The sequence of novel SARS-CoV-2 has been shown to be 75-80% identical to SARS-CoV-1 and 40% identical to MERS-CoV [8] . SARS-CoV-2 and SARS-CoV-1 share the same host receptor, human angiotensin-converting enzyme 2 (ACE2), which is the primary target of the virus.…”