Role of OAS gene family in COVID-19 induced heart failure.

BACKGROUND: COVID-19, the current global pandemic caused by SARS-CoV-2 infection, can damage the heart and lead to heart failure (HF) and even cardiac death. The 2',5'-oligoadenylate synthetase (OAS) gene family encode interferon (IFN)-induced antiviral proteins which is associated with the antiviral immune responses of COVID-19. While the potential association of OAS gene family with cardiac injury and failure in COVID-19 has not been determined. METHODS: The expression levels and biological functions of OAS gene family in SARS-CoV-2 infected cardiomyocytes dataset (GSE150392) and HF dataset (GSE120852) were determined by comprehensive bioinformatic analysis and experimental validation. The associated microRNAs (miRNAs) were explored from Targetscan and GSE104150. The potential OAS gene family-regulatory chemicals or ingredients were predicted using Comparative Toxicogenomics Database (CTD) and SymMap database. RESULTS: The OAS genes were highly expressed in both SARS-CoV-2 infected cardiomyocytes and failing hearts. The differentially expressed genes (DEGs) in the two datasets were enriched in both cardiovascular disease and COVID-19 related pathways. The miRNAs-target analysis indicated that 10 miRNAs could increase the expression of OAS genes. A variety of chemicals or ingredients were predicted regulating the expression of OAS gene family especially estradiol. CONCLUSION: OAS gene family is an important mediator of HF in COVID-19 and may serve as a potential therapeutic target for cardiac injury and HF in COVID-19.

Role of OAS gene family in COVID-19 induced heart failure (preprint)

Background COVID-19, the current global pandemic caused by SARS-CoV-2 infection, can damage the heart and lead to heart failure (HF) and even cardiac death. The 2',5'-oligoadenylate synthetase (OAS) gene family encode interferon (IFN)-induced antiviral proteins which is associated with the antiviral immune responses of COVID-19. While the potential association of OAS family with cardiac injury and failure in COVID-19 has not been determined.Methods The expression levels and biological functions of OAS gene family in SARS-CoV-2 infected cardiomyocytes dataset (GSE150392) and HF dataset (GSE120852) were determined by comprehensive bioinformatic analysis and experimental validation. The associated microRNAs (miRNAs) were explored from Targetscan and GSE104150 databases. The potential OAS gene family-regulatory chemicals or ingredients were predicted using Comparative Toxicogenomics Database (CTD) and SymMap database.Results The OAS genes were highly expressed in both SARS-CoV-2 infected cardiomyocytes and in the failing hearts. The differentially expression genes (DEGs) in the two datasets were enriched in cardiovascular disease and COVID-19 related pathways, respectively. The miRNAs-target analysis indicated that 9 miRNAs could increase the expression of OAS genes. A variety of chemicals or ingredients were predicted regulating the expression of OAS gene family especially estradiol.Conclusion OAS gene family is an important mediator of HF in COVID-19 and may serve as a potential therapeutic target for cardiac injury and HF in COVID-19.

Effects of contextual interactive healthcare training on caregivers of patients with suspected COVID-19 infection: Anxiety, learning achievements, perceived support and self-efficacies during quarantine

Background The contextual and interactive learning research was motivated by the need to enhance the healthcare training effect of caregivers of patients with suspected COVID-19 infection during quarantine. However, there is a lack of effective approaches to integrating mobile contextual learning into interactive learning. Objectives Therefore, this study developed a mobile augmented reality-integration contextual interactive healthcare training system, and then investigated the effects of the proposed system on anxiety, learning effects, perceived support and self-efficacies. Methods To validate the effectiveness of the system, we conducted a quasi-experiment with a sample of 91 caregivers of patients with suspected COVID-19 infection. Results and conclusions Results showed that the experimental group with the developed system was superior to the control group with e-pamphlet instruction in mobile devices, in terms of learning effect, perceived support, self-efficacies and reduction of anxiety during quarantine. Therefore, the mobile contextual interactive healthcare training system could be useful to improve caregivers' self-efficacies as well as their ability to care for patients in the context of COVID-19 infection prevention. Implications This is one of the few studies of the effective approach for technology-enhanced healthcare education in the COVID-19 pandemic. Some corresponding suggestions are proposed: implementing mobile contextual interactive training activities to enhance caregivers' knowledge, skills and self-efficacies;involving social interactions to relieve caregivers' anxiety;providing professional communications and support while facing difficulties in taking care of patients with suspected COVID-19 infection.

Proteomics and metabonomics analyses of Covid-19 complications in patients with pulmonary fibrosis.

Pulmonary fibrosis is a devastating disease, and the pathogenesis of this disease is not completely clear. Here, the medical records of 85 Covid-19 cases were collected, among which fibrosis and progression of fibrosis were analyzed in detail. Next, data independent acquisition (DIA) quantification proteomics and untargeted metabolomics were used to screen disease-related signaling pathways through clustering and enrichment analysis of the differential expression of proteins and metabolites. The main imaging features were lesions located in the bilateral lower lobes and involvement in five lobes. The closed association pathways were FcγR-mediated phagocytosis, PPAR signaling, TRP-inflammatory pathways, and the urea cycle. Our results provide evidence for the detection of serum biomarkers and targeted therapy in patients with Covid-19.

ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal-Oral Routes.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear. Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level. Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results. Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal-oral routes.

Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of 2019-nCov entry (preprint)

Background Leading to a sustained epidemic spread with >40,000 confirmed human infections, including >10,000 deaths, COVID-19 was caused by 2019-nCov and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of 2019-nCov into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of 2019-nCov. Moreover, it has been reported that ACE2 is likely to be the receptor for 2019-nCoV. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited.Methods In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level.Results The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results.Conclusions Based on these findings, we speculated that 2019-nCov could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to 2019-nCov, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.Competing Interest StatementThe authors have declared no competing interest.View Full Text