Gastrointestinal cancers, ACE-2/TMPRSS2 expression and susceptibility to COVID-19

Abstract

Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.

Infection of Human Cells by SARS-CoV-2 and Molecular Overview of Gastrointestinal, Neurological, and Hepatic Problems in COVID-19 Patients

“…TMPRSS2 and ACE-2 co-expression in GI could be the entry route for SARS-CoV-2 virus in absorptive enterocytes of the colon and ileum, resulting in further damage to the mucous membrane barrier, the development of inflammatory cytokine production, and the GI symptoms associated with COVID-19. Expression of ACE2 can be altered by several factors, including GI malignancies, which could also increase the severity of COVID-19 infection due to higher expression of ACE-2 and TMPRSS2 [ 30 ]. These findings suggest that a high expression of ACE2 in the digestive system may be a potential route of infection.…”

SARS-CoV-2 tropism across the upper aerodigestive tract

“…ACE2, a type 1 membrane-bound enzyme located in different epithelial tissues, is involved not only in blood pressure regulation by acting on the renin-angiotensin system, but it is also involved in inflammation and neuro-degeneration. 1 This relationship would be exerted by the SARS-CoV-2 spike (S)-protein, and requires cleavage by TMPRSS2 proteases. Testing ACE2 tissue specificity, Shafiee S et al 1 reported a medium/high expression for respiratory nasopharyngeal epithelial cells, a medium expression for squamous oral epithelium, a medium/high expression for salivary glandular cells, and a medium expression for lymphatic/ squamous tonsillar cells.…”

“…1 This relationship would be exerted by the SARS-CoV-2 spike (S)–protein, and requires cleavage by TMPRSS2 proteases. Testing ACE2 tissue specificity, Shafiee S et al 1 reported a medium/high expression for respiratory nasopharyngeal epithelial cells, a medium expression for squamous oral epithelium, a medium/high expression for salivary glandular cells, and a medium expression for lymphatic/squamous tonsillar cells. 1…”

“…The oral cavity has been identified as a vulnerable target too, with a prevalent ACE2 tongue expression (oral tongue, followed by floor of mouth and tongue base) rather than buccal/gingival tissues. 1…”

“…Salivary glands may act as a target, with ACE2 expression in the tongue even higher than that observed in different anatomic subsites within the aerodigestive tract, 1 suggesting that salivary glands may act as reservoir also in asymptomatic patients. 4…”