Intestinal Damage in COVID-19: SARS-CoV-2 Infection and Intestinal Thrombosis

Wu, Xiaoming; Jing, Haijiao; Wang, Chengyue; Wang, Yufeng; Zuo, Nan; Jiang, Tao; Novakovic, Valerie A.; Shi, Jialan

doi:10.3389/fmicb.2022.860931

Cited by 20 publications

(28 citation statements)

References 107 publications

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“…However, these chips are not the only ones used for research on viral diseases. Given that COVID-19, as well as other coronaviruses, can affect several organs, including kidneys, and the gastrointestinal, cardiovascular and nervous systems [ 90 , 91 , 92 , 93 ], 3D models of other organs have been used. Bein et al [ 94 ] recently modeled an immunocompetent human Intestine-on-a-Chip to study enteric NL63 coronavirus infection and treatment, whereas Helms et al [ 95 ], using kidney organoids derived from pluripotent stem cells, showed that SARS-CoV-2 can directly infect and damage kidney tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

Plebani

Bai²,

et al. 2022

IJMS

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics.

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Section: Discussionmentioning

confidence: 99%

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

Plebani

Bai²,

et al. 2022

IJMS

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“…Ischemic colitis, a rare presentation of SARS-CoV-2 involvement in the colon, has been reported in some cases [138,[183][184][185]. Microscopic examination of these cases showed coagulative mucosal necrosis with crypt apoptosis and small vessel thrombosis, mainly noted in the submucosal vasculature [184].…”

Section: The Effects Of Covid-19 Infection On the Coagulation System ...mentioning

confidence: 97%

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Khreefa

Barbier

Koksal

et al. 2023

Cells

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The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal–oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.

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“…Besides, several lines of evidence support that intestinal infection by SARS-CoV-2 could occur via the bloodstream[ 19 , 26 ]. The virus replicating in pulmonary alveolar epithelial cells or in ciliary cells of the nasal cavity is capable of breaching the basement membrane and causing viremia[ 27 ]. The GI tract comprises an extended network of capillaries harboring vascular epithelial cells, which are potential targets of circulating SARS-CoV-2.…”

Section: Gi Involvement and The Mechanisms Of Intestinal Infection In...mentioning

confidence: 99%

“…The GI tract comprises an extended network of capillaries harboring vascular epithelial cells, which are potential targets of circulating SARS-CoV-2. Thereafter, the proliferating virus is released from the infected cells into the gut, where it can infect neighboring enterocytes or reenter the circulation to generate new cycles of infection[ 27 , 28 ].…”

Section: Gi Involvement and The Mechanisms Of Intestinal Infection In...mentioning

confidence: 99%

“…The pathophysiology underlying CAC is multifactorial, encompassing endothelial injury, over-exuberant immune responses, and overt dysregulation of coagulation and fibrinolytic pathways, which collectively result in a procoagulant state[ 131 ]. The activation of these mechanisms can be further aggravated by defects in intestinal barrier integrity due to SARS-CoV-2 infection[ 27 , 137 ].…”

Section: Gut Barrier Dysfunction Inflaming Covid-19-associated Coagul...mentioning

confidence: 99%

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Intestinal barrier dysfunction as a key driver of severe COVID-19

Tsounis¹,

Triantos²,

Konstantakis³

et al. 2023

World J Virol

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The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with intestinal immune cells and with epithelial and endothelial cells, forming a multi-layered barrier that enables the efficient absorption of nutrients without an excessive influx of pathogens. Despite being a lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including the gastrointestinal tract and the pertinent gut barrier function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can inflict either direct cytopathic injury to intestinal epithelial and endothelial cells or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines the structural integrity of the barrier by modifying the expression of tight junction proteins. In addition, SARS-CoV-2 induces profound alterations to the intestinal microflora at phylogenetic and metabolomic levels (dysbiosis) that are accompanied by disruption of local immune responses. The ensuing dysregulation of the gut-lung axis impairs the ability of the respiratory immune system to elicit robust and timely responses to restrict viral infection. The intestinal vasculature is vulnerable to SARS-CoV-2-induced endothelial injury, which simultaneously triggers the activation of the innate immune and coagulation systems, a condition referred to as “immunothrombosis” that drives severe thrombotic complications. Finally, increased intestinal permeability allows an aberrant dissemination of bacteria, fungi, and endotoxin into the systemic circulation and contributes, to a certain degree, to the over-exuberant immune responses and hyper-inflammation that dictate the severe form of COVID-19. In this review, we aim to elucidate SARS-CoV-2-mediated effects on gut barrier homeostasis and their implications on the progression of the disease.

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Intestinal Damage in COVID-19: SARS-CoV-2 Infection and Intestinal Thrombosis

Cited by 20 publications

References 107 publications

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Intestinal barrier dysfunction as a key driver of severe COVID-19

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