The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19

Ye, Qing; Wang, Bili; Zhang, Ting; Xu, Jian; Shang, Shiqiang

doi:10.1152/ajpgi.00148.2020

Cited by 138 publications

(207 citation statements)

References 76 publications

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“…In addition, epithelial cells of the small intestine is another tissue that highly express ACE2 in cell membrane, 42 creating another potential region for SARS-CoV-2 infection and enteric manifestations of COVID-19. The pathophysiology of these GI symptoms is not well elucidated, but some potential mechanisms are described in a study of Ye et al 47 The most logical mechanism relates the high expression of ACE2 in the epithelial cells of small intestine that may cause a direct viral infection into the bowel. However, this hypothesis remains speculative, as one study found that SARS-CoV-2 was not always detected in stool samples of COVID-19 patients with GI manifestations.…”

Section: Resultsmentioning

confidence: 99%

“… 48 Some studies speculate that the downregulation of ACE2 expression in the epithelial cells of the intestine may affect the absorption of tryptophan – a peptide that belongs to a pathway that regulates the antimicrobial peptides expression and, therefore, the composition of the intestinal flora. 47 Therefore, any dysregulation of this pathway could lead to GI symptoms, such as diarrhea.…”

Section: Resultsmentioning

confidence: 99%

“…Other mechanisms were also discussed in the study by Ye et al, 47 including side effects of antibiotics and the establishment of a gut-lung axis that would allow a immune reaction of a lung infection to be also present in the bowel, causing diarrhea and intestinal immune damage.…”

Section: Resultsmentioning

confidence: 99%

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Extrapulmonary manifestations of COVID-19 in children: a comprehensive review and pathophysiological considerations

Pousa¹,

Mendonça²,

Oliveira³

et al. 2021

Jornal de Pediatria

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Objective The aim of this review was to summarize the most common extrapulmonary manifestations in pediatric patients with COVID-19, as well as to discuss clinical, epidemiological, and pathophysiological aspects of these clinical presentations in children. Source of data An extensive search of literature was performed in order to identify pediatric cases with extrapulmonary manifestations between January 1, 2020 and June 21, 2020. Generic keywords, such as “Novel coronavirus” or “Novel coronavirus 2019” or “2019 nCoV” or “COVID-19” or “SARS-CoV-2” were searched on PubMed database, associated either with age filters or generic pediatric terms. Summary of findings A total of 28 articles, including 199 patients, were considered suitable to review and data extraction. The main findings were summarized in tables. The main non-pulmonary manifestations in pediatric patients, in decreasing order of frequency, were gastrointestinal, renal, cardiovascular, neurological, hematological and lymphatic, cutaneous, hepatic, ocular, olfactory, and gustatory. Multisystem impairment and Kawasaki-like disease were also described. Conclusions Differences in immune response of children and variations of tissue expression of angiotensin converting enzyme 2, the virus receptor, are likely to influence clinical, epidemiological, and pathophysiological patterns of the disease.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Extrapulmonary manifestations of COVID-19 in children: a comprehensive review and pathophysiological considerations

Pousa¹,

Mendonça²,

Oliveira³

et al. 2021

Jornal de Pediatria

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“…intestinal ora fails to regulate the host's immune response, leading to in ammation storm closely associated with lungs and vital organ systems [24][25].…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics, Risk Factors and Predictive Value of COVID-19 Pneumonia: A Retrospective Study of 173 Patients in Wuhan, China

Zhang¹,

Xue²,

Yan³

et al. 2020

Preprint

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Background: COVID-19 is a globally emerging infectious disease. As the global epidemic continues to spread, the risk of COVID-19 transmission and diffusion in the world will also remain. Currently, several studies describing its clinical characteristics have focused on the initial outbreak, but rarely to the later stage. Here we described clinical characteristics, risk factors for disease severity and in-hospital outcome in patients with COVID-19 pneumonia from Wuhan. Methods: Patients with COVID-19 pneumonia admitted to Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 13 to March 8, 2020, were retrospectively enrolled. Multivariable logistic regression analysis was used to identify risk factors for disease severity and in-hospital outcome and establish predictive models. Receiver operating characteristic (ROC) curve was used to assess the predictive value of above models.Results: 106 (61.3%) of the patients were female. The mean age of study populations was 62.0 years, of whom 73 (42.2%) had underlying comorbidities mainly including hypertension (24.9%). The most common symptoms on admission were fever (67.6%) and cough (60.1%), digestive symptoms (22.0%) was also very common. Older age (OR: 3.420; 95%Cl: 1.415-8.266; P=0.006), diarrhea (OR: 0.143; 95%Cl: 0.033-0.611; P=0.009) and lymphopenia (OR: 4.769; 95%Cl: 2.019-11.266; P=0.000) were associated with severe illness on admission; the area under the ROC curve (AUC) of predictive model were 0.860 (95%CI: 0.802-0.918; P=0.000). Older age (OR: 0.309; 95%Cl: 0.142-0.674; P=0.003), leucopenia (OR: 0.165; 95%Cl: 0.034-0.793; P=0.025), increased lactic dehydrogenase (OR: 0.257; 95%Cl: 0.100-0.659; P=0.005) and interleukins-6 levels (OR: 0.294; 95%Cl: 0.099-0.872; P=0.027) were associated with poor in-hospital outcome; AUC of predictive model were 0.752 (95%CI: 0.681-0.824; P=0.000).Conclusion: Older patients with diarrhea and lymphopenia need early identification and timely intervention to prevent the progression to severe COVID-19 pneumonia. However, older patients with leucopenia, increased lactic dehydrogenase and interleukins-6 levels are at a high risk for poor in-hospital outcome.Trial registration: ChiCTR2000029549

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“…In addition, biopsy samples showed a large number of interstitial edema plasma cells and lymphocytes infiltrated into lamina propria of the stomach, duodenum and rectum (7). It has been reported that SARS-CoV-2 can cause acute hemorrhagic colitis, providing the evidence of the gastrointestinal tract implicating in the transmission of SARS-CoV-2 infection (8). Moreover, the viral RNA was identified in stool samples of COVID-19 patients and typical coronavirus virions in rectal tissue were observed under electron microscopy, implying that SARS-CoV-2 could potentially be transmitted via the fecal-oral route (9)(10)(11).…”

Section: Introductionmentioning

confidence: 93%

Modeling SARS-CoV-2 infection in vitro with a human intestine-on-chip device

Guo

Luo

Wang

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has given rise to a global pandemic. The gastrointestinal symptoms of some COVID-19 patients are underestimated. There is an urgent need to develop physiologically relevant model that can accurately reflect human response to viral infection. Here, we report the creation of a biomimetic human intestine infection model on a chip system that allows to recapitulate the intestinal injury and immune response induced by SARS-CoV-2, for the first time. The microengineered intestine-on-chip device contains human intestinal epithelium (co-cultured human intestinal epithelial Caco-2 cells and mucin secreting HT-29 cells) lined in upper channel and vascular endothelium (human umbilical vein endothelial cells, HUVECs) in a parallel lower channel under fluidic flow condition, sandwiched by a porous PDMS membrane coated with extracellular matrix (ECM). At day 3 post-infection of SARS-CoV-2, the intestine epithelium showed high susceptibility to viral infection and obvious morphological changes with destruction of intestinal villus, dispersed distribution of mucus secreting cells and reduced expression of tight junction (E-cadherin), indicating the destruction of mucous layer and the integrity of intestinal barrier caused by virus. Moreover, the endothelium exhibited abnormal cell morphology with disrupted expression of adherent junction protein (VE-cadherin). Transcriptional analysis revealed the abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection (e.g., up-regulated cytokine genes, TNF signaling and NF-kappa B signaling-related genes). This bioengineered in vitro model system can mirror the human relevant pathophysiology and response to viral infection at the organ level, which is not possible in existing in vitro culture systems. It may provide a promising tool to accelerate our understanding of COVID-19 and devising novel therapies.

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The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19

Cited by 138 publications

References 76 publications

Extrapulmonary manifestations of COVID-19 in children: a comprehensive review and pathophysiological considerations

Extrapulmonary manifestations of COVID-19 in children: a comprehensive review and pathophysiological considerations

Clinical Characteristics, Risk Factors and Predictive Value of COVID-19 Pneumonia: A Retrospective Study of 173 Patients in Wuhan, China

Modeling SARS-CoV-2 infection in vitro with a human intestine-on-chip device

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