COVID-19 diarrhea is inflammatory, caused by direct viral effects plus major role of virus-induced cytokines.

CaCC DRA NHE3 SARS-CoV-2 cytokines diarrhea virus like particles

Journal

Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302

Informations de publication

Date de publication:
30 Jul 2024
Historique:
received: 29 01 2024
revised: 08 07 2024
accepted: 23 07 2024
medline: 2 8 2024
pubmed: 2 8 2024
entrez: 1 8 2024
Statut: aheadofprint

Résumé

Diarrhea occurs in up to 50% of cases of COVID-19. Nonetheless, the pathophysiologic mechanism(s) have not been determined. This was examined using normal human enteroid monolayers exposed apically to live SARS-CoV-2 or non-replicating virus like particles (VLPs) bearing the four SARS-CoV-2 structural proteins or irradiated virus, all of which bound and entered enterocytes. Live virus and VLPs increased secretion of multiple cytokines and reduced mRNAs of ACE2, NHE3 and DRA. IL-6 plus IL-8 alone reduced NHE3 mRNA and protein and DRA mRNA. Neither VLPs nor IL-6 plus IL-8 alone altered Cl The pathophysiology of COVID-19 diarrhea appears to be a unique example of a calcium dependent inflammatory diarrhea, that is caused by direct viral effects plus the virus-induced intestinal epithelial cytokine secretion.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Diarrhea occurs in up to 50% of cases of COVID-19. Nonetheless, the pathophysiologic mechanism(s) have not been determined.
METHODS METHODS
This was examined using normal human enteroid monolayers exposed apically to live SARS-CoV-2 or non-replicating virus like particles (VLPs) bearing the four SARS-CoV-2 structural proteins or irradiated virus, all of which bound and entered enterocytes.
RESULTS RESULTS
Live virus and VLPs increased secretion of multiple cytokines and reduced mRNAs of ACE2, NHE3 and DRA. IL-6 plus IL-8 alone reduced NHE3 mRNA and protein and DRA mRNA. Neither VLPs nor IL-6 plus IL-8 alone altered Cl
CONCLUSIONS CONCLUSIONS
The pathophysiology of COVID-19 diarrhea appears to be a unique example of a calcium dependent inflammatory diarrhea, that is caused by direct viral effects plus the virus-induced intestinal epithelial cytokine secretion.

Identifiants

DOI: 10.1016/j.jcmgh.2024.101383 PMID: 39089626
pubmed: 39089626
pii: S2352-345X(24)00138-3
doi: 10.1016/j.jcmgh.2024.101383
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101383

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Mark Donowitz (M)

Department of Medicine, University of New Mexico Center for Global Health; Infectious Diseases, University of New Mexico Center for Global Health. Electronic address: mdonowit@jhmi.edu.

Chung-Ming Tse (CM)

Department of Medicine, University of New Mexico Center for Global Health.

Rafiq Sarker (R)

Department of Medicine, University of New Mexico Center for Global Health.

Ruxian Lin (R)

Department of Medicine, University of New Mexico Center for Global Health.

Karol Dokladny (K)

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, University of New Mexico Center for Global Health.

Manmeet Rawat (M)

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, University of New Mexico Center for Global Health.

Ivy Horwitz (I)

Department of Microbiology and Immunology, Bloomberg School of Public Health of the Johns Hopkins University, University of New Mexico Center for Global Health.

ChunYan Ye (C)

Department of Microbiology and Immunology, Bloomberg School of Public Health of the Johns Hopkins University, University of New Mexico Center for Global Health.

G McNamara (G)

Department of Medicine, University of New Mexico Center for Global Health.

Julie In (J)

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, University of New Mexico Center for Global Health.

Alison Kell (A)

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, University of New Mexico Center for Global Health.

Chenxu Guo (C)

Department of Physiology, University of New Mexico Center for Global Health.

Shang JuiTsai (S)

Department of Physiology, University of New Mexico Center for Global Health.

Tyrus Vong (T)

Department of Medicine, University of New Mexico Center for Global Health.

Andrew Karaba (A)

Divisions of Gastroenterology and Hepatology, University of New Mexico Center for Global Health.

Varsha Singh (V)

Department of Medicine, University of New Mexico Center for Global Health.

Jaiprasath Sachithanandhan (J)

Department of Internal Medicine, University of New Mexico Health Sciences Center, University of New Mexico Center for Global Health.

Andy Pekosz (A)

Department of Internal Medicine, University of New Mexico Health Sciences Center, University of New Mexico Center for Global Health.

Andrea Cox (A)

Divisions of Gastroenterology and Hepatology, University of New Mexico Center for Global Health.

Steven Bradfute (S)

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, University of New Mexico Center for Global Health; Department of Microbiology and Immunology, Bloomberg School of Public Health of the Johns Hopkins University, University of New Mexico Center for Global Health.

Nicholas C Zachos (NC)

Department of Medicine, University of New Mexico Center for Global Health.

Steven Gould (S)

Department of Physiology, University of New Mexico Center for Global Health.

Olga Kovbasnjuk (O)

Department of Medicine, University of New Mexico Center for Global Health; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, University of New Mexico Center for Global Health.

Classifications MeSH