Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process

Abstract

ObjectiveSince December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed.DesignFive datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion.ResultsCell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon.ConclusionThis study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.

COVID-19 and the gastrointestinal tract: more than meets the eye

“…19 ACE2 and TMPRSS2 were not only coexpressed in lung alveolar type 2 cells and oesophageal upper epithelial and gland cells but also highly expressed in the ileum and colon suggesting that the virus can invade enterocytes of the digestive tract. In the oesophagus, ACE2 was highly expressed in the upper and stratified epithelial cells, 8 and this finding may explain SARS-CoV-2 detection in the oesophageal erosion. 7 An intriguing finding was a higher expression of ACE2 in absorptive enterocytes from the ileum and colon than the lung.…”

“…5 In GUT several articles report on GI symptoms, detection of the virus in faeces and potential pathophysiological aspects including viral receptor expression in the GI tract. [6][7][8][9][10][11][12] Two large clinical studies from China focused on GI symptoms and detection of the virus in faeces. 6 7 Jin et al investigated 74 patients infected with SARS-CoV-2 with GI symptoms such as diarrhoea, nausea and vomiting.…”

“…11 To take these findings further, Zhang et al examined ACE2-expressing cell composition and proportion in five public datasets with single-cell transcriptomes of lung, oesophagus, gastric, ileum and colon. 8 They found that successful virus entry of SARS-CoV-2 depends not only on the presence of cell receptor ACE2 but also the cellular serine protease, transmembrane protease serine 2 (TMPRSS2), which cleaves the S protein of human coronaviruses on the cell membrane, both of which are critical for fusion of viral and the cellular membranes. 19 ACE2 and TMPRSS2 were not only coexpressed in lung alveolar type 2 cells and oesophageal upper epithelial and gland cells but also highly expressed in the ileum and colon suggesting that the virus can invade enterocytes of the digestive tract.…”

“…7 An intriguing finding was a higher expression of ACE2 in absorptive enterocytes from the ileum and colon than the lung. 8 It is unclear whether intestinal inflammation exacerbates ACE2 expression in the gut and exerts an increased risk to patients with inflammatory bowel disease. In this issue of GUT, death was reported in an elderly patient with severe acute ulcerative colitis (on mesalazine) who was treated with high dose intravenous corticosteroids and subsequently developed COVID-19 pneumonia.…”

SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids

“…Reliable human in vitro GI model systems that faithfully reproduce infection dynamics and disease mechanisms will prove key to advance our understanding of SARS-CoV-2 replication and pathology in the GI tract. Little information is available with respect to the distribution of the viral receptor angiotensinconverting enzyme 2 (ACE2) at the level of the GI tract of humans 14 . In particular, we lack fundamental information regarding which region of the GI system is the target of replication and primarily associates with the prolonged shedding of SARS-CoV-2 in both pediatric and adult patients.…”