Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.

BackgroundIn recent years novel human respiratory disease agents have been described for Southeast Asia and Australia. The causative pathogens were classified as pteropine orthoreoviruses with a strong phylogenetic relationship to orthoreoviruses of bat origin.ResultsIn this report, we isolated a novel Melaka-like reovirus (named “Cangyuan virus”) from intestinal content samples of one fruit bat residing in China’s Yunnan province. Phylogenetic analysis of the whole Cangyuan virus genome sequences of segments L, M and S demonstrated the genetic diversity of the Cangyuan virus. In contrast to the L and M segments, the phylogenetic trees for the S segments of Cangyuan virus demonstrated a greater degree of heterogeneity.ConclusionsPhylogenetic analysis indicated that the Cangyuan virus was a novel orthoreovirus and substantially different from currently known members of Pteropine orthoreovirus (PRV) species group.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-014-0293-4) contains supplementary material, which is available to authorized users.

1 , the crucial role of angiotensin-converting enzyme 2 (ACE2) in severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), was highlighted. ACE2 is a membrane-bound aminopeptidase that cleaves angiotensin I and angiotensin II into the angiotensin-(1-9) and angiotensin-(1-7) peptides. Several studies support the existence of a cardiovascular-protective ACE2angiotensin-(1-7)-Mas receptor axis 2. ACE2 is overexpressed in heart failure, arterial hypertension and diabetes mellitus 3. Moreover, ACE2 has been identified as a functional receptor for the entry of corona viruses generally, and SARS-CoV-2 specifically, into host cells 4. Given that most of the severe forms of COVID-19 have occurred in elderly patients with cardiovascular comorbidities, Zheng and colleagues speculate about the influence of chronic treatment with blockers of the renin-angiotensin-aldosterone system (RAAS) on the severity of the infection, stating that "ACE2 levels can be increased by the use of renin-angiotensin-aldosterone system inhibitors" 1. Consequently, the authors suggest that "the safety and potential effects of antihypertension therapy with ACE inhibitors or angiotensin-receptor blockers in patients with COVID-19 should be carefully considered". We wish to clarify that different RAAS inhibitors have different effects on ACE2 levels. By acting at different levels of the system, RAAS inhibitors result in heterogeneous effects on the peptides and enzymes involved. Whereas angiotensin-receptor blockers and mineralocorticoid-receptor blockers have been shown to increase the levels of ACE2 expression and activity in various experimental and clinical models 5,6 , administration of ACE inhibitors increased cardiac Ace2 mRNA levels but had no effect on ACE2 activity in experimental models 7,8. In addition, in an animal model of diabetic nephropathy, the chronic administration of aliskiren (a direct inhibitor of renin) was associated with a reduction in ACE2 expression 9. For these reasons, we believe that chronic treatment

Aims The co‐morbidities contribute to the inferior prognosis of COVID‐19 patients. Recent reports suggested that the higher co‐morbidity rate between COVID‐19 and heart failure (HF) leads to increased mortality. However, the common pathogenic mechanism between them remained elusive. Here, we aimed to reveal underlying molecule mechanisms and genetic correlation between COVID‐19 and HF, providing a new perspective on current clinical management for patients with co‐morbidity. Methods The gene expression profiles of HF (GSE26887) and COVID‐19 (GSE147507) were retrieved from the GEO database. After identifying the common differentially expressed genes (|log2FC| > 1 and adjusted P < 0.05), integrated analyses were performed, namely, enrichment analyses, protein–protein interaction network, module construction, critical gene identification, and functional co‐expression analysis. The performance of critical genes was validation combining hierarchical clustering, correlation, and principal component analysis in external datasets (GSE164805 and GSE9128). Potential transcription factors and miRNAs were obtained from the JASPER and RegNetwork repository used to construct co‐regulatory networks. The candidate drug compounds in potential genetic link targets were further identified using the DSigDB database. Results The alteration of 12 genes was identified as a shared transcriptional signature, with the role of immune inflammatory pathway, especially Toll‐like receptor, NF‐kappa B, chemokine, and interleukin‐related pathways that primarily emphasized in response to SARS‐CoV‐2 complicated with HF. Top 10 critical genes (TLR4, TLR2, CXCL8, IL10, STAT3, IL1B, TLR1, TP53, CCL20, and CXCL10) were identified from protein–protein interaction with topological algorithms. The unhealthy microbiota status and gut–heart axis in co‐morbidity were identified as potential disease roads in bridging pathogenic mechanism, and lipopolysaccharide acts as a potential marker for monitoring HF during COVID‐19. For transcriptional and post ‐ transcriptional levels, regulation networks tightly coupling with both disorders were constructed, and significant regulator signatures with high interaction degree, especially FOXC1, STAT3, NF‐κB1, miR‐181, and miR‐520, were detected to regulate common differentially expressed genes. According to genetic links targets, glutathione‐based antioxidant strategy combined with muramyl dipeptide‐based microbe‐derived immunostimulatory therapies was identified as promising anti‐COVID‐19 and anti‐HF therapeutics. Conclusions This study identified shared transcriptomic and corresponding regulatory signatures as emerging therapeutic targets and detected a set of pharmacologic agents targeting genetic links. Our findings provided new insights for underlying pathogenic mechanisms between COVID‐19 and HF.