Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

View ORCID ProfileAshutosh Kumar, Muneeb A. Faiq, Vikas Pareek, Khursheed Raza, Ravi K. Narayan, Pranav Prasoon, Pavan Kumar, Maheswari Kulandhasamy, Chiman Kumari, Kamla Kant, Himanshu N. Singh, Rizwana Qadri, Sada N. Pandey, Santosh Kumar
doi: https://doi.org/10.1101/2020.04.14.040204
Ashutosh Kumar
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
2Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Patna, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ashutosh Kumar
  • For correspondence: aiims.ashu@gmail.com
Muneeb A. Faiq
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
3New York University (NYU) Langone Health Center, NYU Robert I Grossman School of Medicine, New York, New York, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vikas Pareek
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
4National Brain Research Center, Manesar, Haryana, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Khursheed Raza
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
5Department of Anatomy, All India Institute of Medical Sciences, Deoghar, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ravi K. Narayan
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
2Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Patna, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pranav Prasoon
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
6Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pavan Kumar
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
7Department of Pediatrics, Medical University of South Carolina, Charleston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maheswari Kulandhasamy
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
8Department of Biochemistry, Maulana Azad Medical College (MAMC), New Delhi, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chiman Kumari
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
9Department of Anatomy, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kamla Kant
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
10Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Bhatinda, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Himanshu N. Singh
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
11TAGC-INSERM, U1090, Aix Marseille University, Marseille, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rizwana Qadri
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
12Neuro-oncology Laboratory, Rockefeller University, New York, New York, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sada N. Pandey
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
13Department of Zoology, Banaras Hindu University (BHU), Varanasi, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Santosh Kumar
1Etiologically Elusive Disorders Research Network (EEDRN), New Delhi, India
14Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Introduction COVID-19, is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structure on its surface called the S-spike. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variation of ACE2 expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms.

Materials and Methods The data were downloaded from the Human Protein Atlas available at (https://www.proteinatlas.org/search/ACE2) and the tissue specific expression (both mRNA and protein) of ACE2 as yielded from the studies with RNA sequencing and immunohistochemistry (IHC) was analyzed as a function of the various components of the digestive tract. A digestive system specific functional enrichment map of ACE2 gene was created using g:profiler (https://biit.cs.ut.ee/gprofiler/gost) utility and the data were visualized using Cytoscape software, version 3.7.2 (https://cytoscape.org/).

Results The correlated expression (genomic and proteomic) of ACE2 (to which SARS-CoV-2 binds through the S-spike) was found to be enriched in the lower gastrointestinal tract (GIT) (highest in small intestine, followed by colon and rectum), and was undetectable in the upper GIT components: mouth cavity (tongue, oral mucosa, and salivary glands), esophagus, and stomach. High expression of ACE2 was noted in the glandular cells as well as in the enterocytes in the lining epithelium (including brush border epithelium). Among other digestive system organs, gallbladder (GB) showed high expression of ACE2 in glandular cells, while any protein expression was undetectable in liver and pancreas.

Conclusions Based on the findings of this study and supportive evidence from the literature we propose that a SARS-CoV-2 binding with ACE2 mediates dysregulation of the sodium dependent nutrient transporters and hence may be a plausible basis for the digestive symptoms in COVID-19 patients. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients.

Highlights

  • SARS-CoV-2 binding receptor ACE2 expression is enriched in human intestine

  • ACE2 regulates neutral amino acid (B0AT1) and glucose transporter (SGLT1) in intestinal epithelium

  • Mucus secreted from GI cells may protect SARS-CoV-2 from harsh pH levels of the digestive juices

  • Continued replication of SARS-CoV-2 in GI cells may cause disease recurrence

Figure
  • Download figure
  • Open in new tab

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 15, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients
Ashutosh Kumar, Muneeb A. Faiq, Vikas Pareek, Khursheed Raza, Ravi K. Narayan, Pranav Prasoon, Pavan Kumar, Maheswari Kulandhasamy, Chiman Kumari, Kamla Kant, Himanshu N. Singh, Rizwana Qadri, Sada N. Pandey, Santosh Kumar
bioRxiv 2020.04.14.040204; doi: https://doi.org/10.1101/2020.04.14.040204
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients
Ashutosh Kumar, Muneeb A. Faiq, Vikas Pareek, Khursheed Raza, Ravi K. Narayan, Pranav Prasoon, Pavan Kumar, Maheswari Kulandhasamy, Chiman Kumari, Kamla Kant, Himanshu N. Singh, Rizwana Qadri, Sada N. Pandey, Santosh Kumar
bioRxiv 2020.04.14.040204; doi: https://doi.org/10.1101/2020.04.14.040204

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Pathology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3607)
  • Biochemistry (7581)
  • Bioengineering (5529)
  • Bioinformatics (20809)
  • Biophysics (10338)
  • Cancer Biology (7988)
  • Cell Biology (11647)
  • Clinical Trials (138)
  • Developmental Biology (6611)
  • Ecology (10217)
  • Epidemiology (2065)
  • Evolutionary Biology (13630)
  • Genetics (9550)
  • Genomics (12854)
  • Immunology (7925)
  • Microbiology (19555)
  • Molecular Biology (7668)
  • Neuroscience (42147)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2203)
  • Physiology (3269)
  • Plant Biology (7051)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1952)
  • Systems Biology (5429)
  • Zoology (1119)