Acute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice

Author:

Hussain Hussain12,Elumalai Nila1ORCID,Sampath Natarajan3ORCID,Shamaladevi Nagarajarao4,Hajjar Rima1ORCID,Druyan Brian Zachary1,Rashed Amirah B.1ORCID,Ramamoorthy Rajalakshmi1,Kenyon Norma S.5,Jayakumar Arumugam R.1ORCID,Paidas Michael J.16

Affiliation:

1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA

2. Department of Internal Medicine, HCA Florida Kendall Hospital, Miami, FL 33175, USA

3. School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, India

4. Molecular Analytics, Miami, FL 33187, USA

5. Microbiology & Immunology and Biomedical Engineering, Diabetes Research Institute, University of Miami, Miami, FL 33136, USA

6. Department of Biochemistry and Molecular Biology, The University of Miami Miller School of Medicine, Miami, FL 33136, USA

Abstract

The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.

Funder

University of Miami Miller School of Medicine Department Obstetrics, Gynecology and Reproductive Sciences, Muriel, Murray & Robert Smith Foundation COVID-19 Research Fund

University of Miami Miller School of Medicine Team Science Award

Charles M. Vallee Foundation

Publisher

MDPI AG

Reference44 articles.

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