scholarly journals COVID-19 Anosmia: High Prevalence, Plural Neuropathogenic Mechanisms, and Scarce Neurotropism of SARS-CoV-2?

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2225
Author(s):  
Fengyi Liang ◽  
De Yun Wang
Keyword(s):  
Small Area ◽  
Respiratory Virus ◽  
Respiratory Epithelium ◽  
Causative Pathogen ◽  
High Susceptibility ◽  
Angiotensin Converting Enzyme 2 ◽  
Cellular Targets ◽  
Sustentacular Cells ◽  
High Prevalence ◽  
Transmembrane Serine Protease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 2019 (COVID-19). It is known as a respiratory virus, but SARS-CoV-2 appears equally, or even more, infectious for the olfactory epithelium (OE) than for the respiratory epithelium in the nasal cavity. In light of the small area of the OE relative to the respiratory epithelium, the high prevalence of olfactory dysfunctions (ODs) in COVID-19 has been bewildering and has attracted much attention. This review aims to first examine the cytological and molecular biological characteristics of the OE, especially the microvillous apical surfaces of sustentacular cells and the abundant SARS-CoV-2 receptor molecules thereof, that may underlie the high susceptibility of this neuroepithelium to SARS-CoV-2 infection and damages. The possibility of SARS-CoV-2 neurotropism, or the lack of it, is then analyzed with regard to the expression of the receptor (angiotensin-converting enzyme 2) or priming protease (transmembrane serine protease 2), and cellular targets of infection. Neuropathology of COVID-19 in the OE, olfactory bulb, and other related neural structures are also reviewed. Toward the end, we present our perspectives regarding possible mechanisms of SARS-CoV-2 neuropathogenesis and ODs, in the absence of substantial viral infection of neurons. Plausible causes for persistent ODs in some COVID-19 convalescents are also examined.

scholarly journals A review of the reasons for high prevalence and rapid progression of COVID-19 in men

2021 ◽  
Vol 7 (1) ◽  
pp. e03-e03
Author(s):  
Neda Taghizabet ◽  
Fatemeh Rezaei-Tazangi ◽  
Hossein Roghani‐Shahraki
Keyword(s):  
Transmembrane Protein ◽  
Rapid Progression ◽  
Acute Type ◽  
Converting Enzyme ◽  
Immune Functions ◽  
Male And Female ◽  
Angiotensin Converting Enzyme 2 ◽  
High Prevalence ◽  
Hormonal Levels

Previous studies have demonstrated a relationship between gender and COVID-19 outcomes. In addition, this is confirmed that men have more danger of progressing an acute type of the illness than women, specifies the significance of miscellaneous data related to male and female patients with COVID-19. In other words, some factors like hormonal levels and immune function may interact with each other. A perception of the fundamental reasons for gender diversities in COVID-19 patients can beget a chance for disease prevention and faster treatment. The present study evaluates the role of gender in the incidence and progression of the COVID-19 disease. It has been explained that how gender affects angiotensin-converting enzyme 2 (ACE2), which is a basic factor for the COVID-19 pathogenesis introducing the sex diversities in platelet function, immune reactions and how sex hormones affect immune functions, also the effect of androgens on transmembrane protein serine protease 2 (TMPRSS2) receptor in COVID-19 patients was investigated.

scholarly journals COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jana Ihlow ◽  
Alexander Seelhoff ◽  
Victor M. Corman ◽  
Achim D. Gruber ◽  
Simon Dökel ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Damage ◽  
Cathepsin L ◽  
Fatal Case ◽  
Clinical Signs ◽  
Angiotensin Converting Enzyme 2 ◽  
Severe Liver Damage ◽  
Severe Jaundice ◽  
Transmembrane Serine Protease

Abstract Background The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. Case presentation Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). Conclusion Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

scholarly journals Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

2020 ◽  
Vol 10 (10) ◽  
pp. 666
Author(s):  
Debasmita Mukhopadhyay ◽  
Bashair M. Mussa
Keyword(s):  
In Silico ◽  
Binding Capacity ◽  
Therapeutic Targets ◽  
In Silico Analysis ◽  
Neurological Impairment ◽  
Essential Elements ◽  
Cell Entry ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Serine Protease ◽  
Silico Analysis

Background: Neuroinvasion of severe acute respiratory syndrome coronavirus (SARS-CoV) is well documented and, given the similarities between this virus and SARS-CoV-2, it seems that the neurological impairment that is associated with coronavirus disease 2019 (COVID-19) is due to SARS-CoV-2 neuroinvasion. Hypothalamic circuits are exposed to the entry of the virus via the olfactory bulb and interact centrally with crucial respiratory nuclei. Hypothalamic microRNAs are considered as potential biomarkers and modulators for various diseases and future therapeutic targets. The present study aims to investigate the microRNAs that regulate the expression of hypothalamic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential elements for SARS-CoV-2 cell entry. Methods: To determine potential hypothalamic miRNAs that can directly bind to ACE2 and TMPRSS2, multiple target bioinformatics prediction algorithms were used, including miRBase, Target scan, and miRWalk2.029. Results: Our in silico analysis has revealed that, although there are over 5000 hypothalamic miRNAs, around 31 miRNAs and 29 miRNAs have shown binding sites and strong binding capacity against ACE2 and TMPRSS2, respectively. Conclusion: These novel potential hypothalamic miRNAs can be used to identify new therapeutic targets to treat neurological symptoms in COVID-19 patients via regulation of ACE2 and TMPRSS2 expression.

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

scholarly journals COVID-19 and androgen-targeted therapy for prostate cancer patients

2020 ◽  
Vol 27 (9) ◽  
pp. R281-R292 ◽  
Author(s):  
Neil A Bhowmick ◽  
Jillian Oft ◽  
Tanya Dorff ◽  
Sumanta Pal ◽  
Neeraj Agarwal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Viral Entry ◽  
Host Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Cancer Management ◽  
Signaling Inhibitors ◽  
Androgen Regulation ◽  
Androgen Suppression ◽  
Transmembrane Serine Protease ◽  
Significant Disease

The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.

scholarly journals SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

2020 ◽  
Author(s):  
Leon Fodoulian ◽  
Joel Tuberosa ◽  
Daniel Rossier ◽  
Madlaina Boillat ◽  
Chenda Kan ◽  
...  
Keyword(s):  
Sensory System ◽  
Cell Types ◽  
Sensory Epithelium ◽  
Brain Cell ◽  
Rna Seq ◽  
Angiotensin Converting Enzyme 2 ◽  
Sustentacular Cells ◽  
The Brain ◽  
Brain Cell Types ◽  
Human And Mouse

AbstractVarious reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

scholarly journals Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253489
Author(s):  
Anna Goc ◽  
Waldemar Sumera ◽  
Matthias Rath ◽  
Aleksandra Niedzwiecki
Keyword(s):  
Phenolic Compounds ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Cathepsin L ◽  
Converting Enzyme ◽  
Cellular Mechanisms ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Attachment ◽  
Cellular Entry ◽  
Transmembrane Serine Protease

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3’-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3’-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3’-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3’-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.

scholarly journals Critical appraisal of the mechanisms of gastrointestinal and hepatobiliary infection by COVID-19

2021 ◽  
Author(s):  
Emile Levy ◽  
Alain Stintzi ◽  
Albert Cohen ◽  
Yves Desjardins ◽  
Andre Marette ◽  
...  
Keyword(s):  
Disease Transmission ◽  
Critical Appraisal ◽  
Infectious Virus ◽  
Oral Route ◽  
Intestinal Epithelial ◽  
Angiotensin Converting Enzyme 2 ◽  
Risk Of Disease ◽  
Transmembrane Serine Protease ◽  
The Impact ◽  
Critical Overview

COVID-19 represents a novel infectious disease induced by SARS-CoV-2. It has to date affected 24,240,000 individuals and killed 2,735,805 people worldwide. The highly infectious virus attacks mainly the lung causing fever, cough and fatigue in symptomatic patients, but also pneumonia in severe cases. However, growing evidence highlights SARS-CoV-2-mediated extra-respiratory manifestations, namely gastrointestinal (GI) and hepatic complications. The detection of (i) the virus in the GI system (duodenum, colon, rectum, anal region and feces); (ii) the high expression of additional candidate co-receptors/auxiliary proteins to facilitate the virus entry; (iii) the abundant viral angiotensin-converting enzyme 2 receptor; (iv) the substantial expression of host transmembrane serine protease 2, necessary to induce virus-cell fusion; (v) the viral replication in the intestinal epithelial cells; and (vi) the primarily GI disorders in the absence of respiratory symptoms lead to increased awareness of the risk of disease transmission via the fecal-oral route. The objectives of this review are to provide a brief update of COVID-19 pathogenesis and prevalence, present a critical overview of its GI and liver complications that affect clinical COVID-19 outcomes, clarify associated mechanisms (notably microbiota-related), define whether gut/liver disorders occur more frequently among critically ill patients with COVID‐19, determine the impact of COVID-19 on pre-existing gut/liver complications and vice versa, and discuss the available strategies for prevention and treatment to improve prognosis of the patients.

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