Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs

Xu, Jiabin; Chu, Mei; Zhong, Fan; Tan, Xinghua; Tang, Guosheng; Mai, Jianbo; Lai, Niangmei; Guan, Chenyu; Liang, Yujie; Liao, Guiqing

doi:10.1038/s41420-020-00307-w

Cited by 87 publications

(79 citation statements)

References 33 publications

(40 reference statements)

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“…Additionally, different studies have demonstrated that 5–10% of COVID-19 patients present digestive symptoms, such as abdominal pain, vomits, and diarrhea, as well as intestinal inflammation [ 19 , 20 , 21 , 22 ]. These data suggest that the gastrointestinal tract might be a location of viral activity and replication, which agrees with the high expression of ACE2 in the intestinal epithelium [ 23 , 24 , 25 , 26 ]. ACE2 is recognized as an important regulator of the renin-angiotensin system (RAS) by counteracting the negative actions mediated by Angiotensin II signaling via its type 1 receptor [ 27 ].…”

Section: The “Gut Microbiota Hypothesis” In Poor Outcomes Of Covidsupporting

confidence: 72%

Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update

2020

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The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response; (ii) the fact that 5–10% of the patients present gastrointestinal symptoms; and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system’s hyperresponsiveness and a severe inflammatory condition (collectively referred as “cytokine storm”) are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.

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Section: The “Gut Microbiota Hypothesis” In Poor Outcomes Of Covidsupporting

confidence: 72%

Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update

2020

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“… 42 Similarly, Xu et al also indicated that digestive tract organs had higher ACE2 expression levels compared to the lung based on a series of bulk and single-cell RNA sequencing data. 43 Also, chromatin accessibility and RNA transcript levels reveal a tissue-specific expression pattern for Ace 2 and Tmprss2 (Transmembrane Serine Protease 2), with greatest expression observed in intestine, kidney, and lung tissues. 44 Furthermore, ACE2 expression was gradually increased from chronic gastric to metaplasia, to early cancer, and was higher in tumor cells compared to normal controls.…”

Section: Covid-19 and Gastrointestinal Dysfunctionsmentioning

confidence: 99%

“…44 Furthermore, ACE2 expression was gradually increased from chronic gastric to metaplasia, to early cancer, and was higher in tumor cells compared to normal controls. 43 These data may explain the differences in severity of COVID-19 symptoms, including digestive symptoms, in people as some are asymptomatic while some are fatal. The SARS-CoV-2 infection was more severe in patients with comorbidities, which may be correlated with increased ACE2 expression and susceptibility to SARS-CoV-2 infection.…”

Section: Covid-19 and Gastrointestinal Dysfunctionsmentioning

confidence: 99%

Gastrointestinal symptoms, pathophysiology, and treatment in COVID-19

2021

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The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and is responsible for the Coronavirus Disease 2019 global pandemic. Coronaviruses, including SARS-CoV-2, are strongly associated with respiratory symptoms during infection, but gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain, have been identified in subsets of COVID-19 patients. This article focuses on gastrointestinal symptoms and pathophysiology in COVID-19 disease. Evidence suggests that the gastrointestinal tract could be a viral target for SARS-CoV-2 infection. Not only is the SARS-CoV-2 receptor ACE2 highly expressed in the GI tract and is associated with digestive symptoms, but bleeding and inflammation are observed in the intestine of COVID-19 patients. We further systemically summarize the correlation between COVID-19 disease, gastrointestinal symptoms and intestinal microbiota. The potential oral-fecal transmission of COVID-19 was supported by viral RNA and live virus detection in the feces of COVID-19 patients. Additionally, the viral balance in the GI tract could be disordered during SARS-CoV-2 infection which could further impact the homeostasis of the gut microbial flora. Finally, we discuss the clinical and ongoing trials of treatments/therapies, including antiviral drugs, plasma transfusion and immunoglobulins, and diet supplementations for COVID-19. By reviewing the pathogenesis of SARS-CoV-2 virus, and understanding the correlation among COVID-19, inflammation, intestinal microbiota, and lung microbiota, we provide perspective in prevention and control, as well as diagnosis and treatment of the COVID-19 disease.

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“…The pathomechanism underlying persistence of these symptoms after SARS-CoV-2-infection is matter of debate and investigation. Microangiopathic cerebral lesions (42), effects directly mediated by the virus (38,43), and immune-mediated in ammatory syndromes (44) are proposed to play a role. Previous studies reported on the correlation of high antibody titers with more severe course of acute COVID-19 (5,21).…”

Section: Discussionmentioning

confidence: 99%

Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19

Bilich¹,

Nelde²,

Maringer³

et al. 2020

Preprint

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Long-term immunity to SARS-CoV-2 is crucial for the development of herd immunity and the aim of vaccination approaches. Reports on rapidly decreasing antibody titers question the efficacy of humoral immunity. The relevance of T cell memory after COVID-19 is yet unclear. Longitudinal analysis of SARS-CoV-2 immunity in convalescents up to six months post-infection revealed decreasing and stable spike and nucleocapsid antibody responses, respectively. In contrast, T cell responses remained robust and even increased in frequency and intensity. Single epitope mapping of T cell diversity over time identified ORF-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses and may be fundamental for vaccine design.

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Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs

Cited by 87 publications

References 33 publications

Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update

Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update

Gastrointestinal symptoms, pathophysiology, and treatment in COVID-19

Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19

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