Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

Kumar, Ashutosh; Faiq, Muneeb A.; Pareek, Vikas; Raza, Khursheed; Narayan, Ravi Kant; Prasoon, Pranav; Kumar, Pavan; Kulandhasamy, Maheswari; Kumari, Chiman; Kant, Kamla; Singh, Himanshu Narayan; Qadri, Rizwana; Pandey, Sada N.; Kumar, Santosh

doi:10.1016/j.mehy.2020.110271

Cited by 52 publications

(57 citation statements)

References 51 publications

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“…5 Moreover, downregulation of ACE2 following the endocytosis of the virus complex results in increased angiotensin II concentrations, which are known to impede insulin secretion. 6,7 Similar to what happens with other viral infections, an immune-mediated beta-cell destruction triggered by the SARS-CoV-2 infection has been also suggested. 4,7 In a parallel way, highlighted that ACE2-mediated downregulation of SGLT1 in the intestinal epithelium has the potential to improve glycaemic status in an experimental model of T1D.…”

Section: Hypothesismentioning

confidence: 68%

“…9 Inversely, ACE2-mediated SGLT1 upregulation occurs in diabetes and diabetes-related diseases, which results in increased intestinal glucose absorption and subsequently to the development of hyperglycemia. 6 In support of the perspective that SGLT1 might be implicated in the metabolic disarrangement observed in some patients with COVID-19, Dai et al 10 phlorizin was correlated with a decreased survival rate in a rat model of bronchial inflammation and sepsis. 12 SGLT activation has recently been a key therapeutic target in T2D, where excessive glucose reabsorption by the kidneys is observed.…”

Section: Hypothesismentioning

confidence: 94%

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Intestinal SGLT1 as a therapeutic target in COVID‐19‐related diabetes: A “two‐edged sword” hypothesis

Koufakis

Metallidis

Zebekakis

et al. 2021

Brit J Clinical Pharma

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Emerging data are linking coronavirus disease 2019 (COVID‐19) with an increased risk of developing new‐onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID‐19‐induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium‐glucose co‐transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium‐dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID‐19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID‐19 outweigh potential risks, particularly with respect to drug‐induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

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Section: Hypothesismentioning

confidence: 68%

Section: Hypothesismentioning

confidence: 94%

Intestinal SGLT1 as a therapeutic target in COVID‐19‐related diabetes: A “two‐edged sword” hypothesis

Koufakis

Metallidis

Zebekakis

et al. 2021

Brit J Clinical Pharma

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“…Nitric oxide-mediated S-nitro-sylation of viral cysteine proteases and host serine protease, TMPRSS2, which are both critical in viral cellular entry, appear to be nitric oxide sensitive [ 60 , 63 , 64 ]. COVID-19 patients often experience periodontal disease [ 65 , 66 ], and vascular [ 67 , 68 ] and gastrointestinal (GI) [ 69 , 70 ] complications, perhaps because ACE2 receptors are widely expressed among these tissues [ 71 , 72 ]. A hyposalivation symptom is exhibited highly in COVID-19 patients [ 73 , 74 ].…”

Section: Mechanism Of Infection In Oral and Overall Body Healthmentioning

confidence: 99%

SARS-CoV-2 Infection and Oral Health: Therapeutic Opportunities and Challenges

Coke

Davison

Fields

et al. 2021

JCM

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The novel corona virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and the disease it causes, COVID-19 (Coronavirus Disease-2019) have had multi-faceted effects on a number of lives on a global scale both directly and indirectly. A growing body of evidence suggest that COVID-19 patients experience several oral health problems such as dry mouth, mucosal blistering, mouth rash, lip necrosis, and loss of taste and smell. Periodontal disease (PD), a severe inflammatory gum disease, may worsen the symptoms associated with COVID-19. Routine dental and periodontal treatment may help decrease the symptoms of COVID-19. PD is more prevalent among patients experiencing metabolic diseases such as obesity, diabetes mellitus and cardiovascular risk. Studies have shown that these patients are highly susceptible for SARS-CoV-2 infection. Pro-inflammatory cytokines and oxidative stress known to contribute to the development of PD and other metabolic diseases are highly elevated among COVID-19 patients. Periodontal health may help to determine the severity of COVID-19 infection. Accumulating evidence shows that African-Americans (AAs) and vulnerable populations are disproportionately susceptible to PD, metabolic diseases and COVID-19 compared to other ethnicities in the United States. Dentistry and dental healthcare professionals are particularly susceptible to this virus due to the transferability via the oral cavity and the use of aerosol creating instruments that are ubiquitous in this field. In this review, we attempt to provide a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the various effects it has had on the dental profession and patients visits to dental clinics. Finally, this review is a valuable resource for the management of oral hygiene and reduction of the severity of infection.

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“…To sum up, there are several evidences coming from different research labs and clinical studies which claim the potential capability of SARS-CoV-2 to infect the GIT by a specific mechanism, and it seems that ACE2 and TMPRSS2 are main players in this mechanism. But, how could SARS-CoV-2 provoke GIT disorders is still to be elucidated, it could be the binding of the virus on the apical surface of intestinal enterocytes mediated by ACE2-TMPRSS2 system may cause a deregulation of the sodium dependent transmembrane transporters such as Na + /H + exchangers (NHEs) and sodium-glucose transport protein (SGLT1) located along the intestine that results in GIT manifestations such as diarrhea and abdominal pain [ 30 , 31 ]. However, further research is necessary to validate such hypothesis.…”

Section: Tmprss2 and Sars-cov-2 Infection Of Gastrointestinal Tract Systemmentioning

confidence: 99%

Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

Mahmoud

Jarrar

2021

Mol Biol Rep

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The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, metastasis and viral infections. Recent studies have shown that TMPRSS2 expressed on cell surface of host cells could play a crucial role in activation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein which facilitates the rapid early entry of the virus into host cells. In addition, direct suppression of TMPRSS2 using small drug inhibitors has been demonstrated to be effective in decreasing SARS-CoV-2 infection in vitro, which presents TMPRSS2 protease as a potential therapeutic strategy for SARS-CoV-2 infection. Recently, SARS-CoV-2 has been shown to be capable of infecting gastrointestinal enterocytes and to provoke gastrointestinal disorders in patients with COVID-19 disease, which is considered as a new transmission route and target organ of SARS-CoV-2. In this review, we highlight the biochemical properties of TMPRSS2 protease and discuss the potential targeting of TMPRSS2 by inhibitors to prevent the SARS-CoV-2 spreading through gastro-intestinal tract system as well as the hurdles that need to be overcome.

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Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

Abstract: Graphical abstract

Cited by 52 publications

References 51 publications

Intestinal SGLT1 as a therapeutic target in COVID‐19‐related diabetes: A “two‐edged sword” hypothesis

Intestinal SGLT1 as a therapeutic target in COVID‐19‐related diabetes: A “two‐edged sword” hypothesis

SARS-CoV-2 Infection and Oral Health: Therapeutic Opportunities and Challenges

Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

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