Network perturbation analysis in human bronchial epithelial cells following SARS-CoV2 infection

Abstract

Background SARS-CoV2, the agent responsible for the current pandemic, is also causing respiratory distress syndrome (RDS), hyperinflammation and high mortality. It is critical to dissect the pathogenetic mechanisms in order to reach a targeted therapeutic approach. Methods In the present investigation, we evaluated the effects of SARS-CoV 2 on human bronchial epithelial cells (HBEC). We used RNA-seq datasets available online for identifying SARS-CoV 2 potential genes target on human bronchial epithelial cells. RNA expression levels and potential cellular gene pathways have been analyzed. In order to identify possible common strategies among the main pandemic viruses, such as SARS-CoV 2 , SARS-CoV1, MERS-CoV, and H1N1, we carried out a hypergeometric test of the main genes transcribed in the cells of the respiratory tract exposed to these viruses. Results The analysis showed that two mechanisms are highly regulated in HBEC: the innate immunity recruitment and the disassembly of cilia and cytoskeletal structure. The granulocyte colony-stimulating factor ( CSF3 ) and dynein heavy chain 7, axonemal ( DNAH7 ) represented respectively the most upregulated and downregulated genes belonging to the two mechanisms highlighted above. Furthermore, the carcinoembryonic antigen-related cell adhesion molecule 7 ( CEACAM7 ) that codifies for a surface protein is highly specific of SARS-CoV 2 and not for SARS-CoV1, MERS-CoV, and H1N1, suggesting a potential role in viral entry. In order to identify potential new drugs, using a machine learning approach, we highlighted Flunisolide, Thalidomide, Lenalidomide, Desoximetasone, xylazine, and salmeterol as potential drugs against SARS-CoV 2 infection. Conclusions Overall, lung involvement and RDS could be generated by the activation and down regulation of diverse gene pathway involving respiratory cilia and muscle contraction, apoptotic phenomena, matrix destructuration, collagen deposition, neutrophil and macrophages recruitment.

Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data

“…Gene DNAH7 encodes dynein axonemal heavy chain 7, which is a component of the inner dynein arm of ciliary axonemes [ 33 ]. A recently published paper showed that gene DNAH7 is the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV2 [ 34 ]. The authors of that study speculated that the downregulation of gene DNAH7 causes the reduction of function of respiratory cilia.…”

Chest radiographs may assist in predicting the outcome in the early phase of Covid-19. UK district general hospital experience of Covid-19 first wave

“…However, these methods do not provide insight into the severity of infection. Computed tomography (CT), lung pathology, and biomarkers have all been suggested to provide concurrent diagnostic and risk stratification assistance [ 8 ]. The application of CT to disease staging is now in worldwide use where it is available; however, chest radiography is a simpler, cheaper, more widely available resource.…”

COVID‑19‑associated meningoencephalitis: A care report and literature review

“…The therapy for COVID-19 remains to be established, although non-pharmacological and preventive treatments have been recommended (5). Like other coronaviruses, SARS-CoV-2 is neurotropic (6). Neurological complications of COVID-19 include cerebrovascular disease, meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy and Guillain-Barré syndrome (7).…”