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Intestines and COVID-19

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#coronavirus #intestines #pandemic #quarantine #diarrhea
Information about authors

Rakhmetova Venera Sametovna, Doctor of Medical Sciences, Professor of the Department of Internal Medicine with a course of nephrology, hematology, allergology and immunology

NJSC "Astana Medical University"

(010000, Republic of Kazakhstan, Nur-Sultan, 49a Beibitshilik st., E-mail:

Malgazdarova Halima Daniyargyzy, intern doctor

NJSC "Astana Medical University"

(010000, Republic of Kazakhstan, Nur-Sultan, Beibitshilik street 49a, e-mail:


The World Health Organization has declared a pandemic outbreak of COVID-19 coronavirus infection, which was first reported in December 2019 in Wuhan, China [1]. Coronavirus infection is an acute viral disease caused by an RNA-containing virus of the genus Betacoronavirus of the family Coronaviridae. Coronavirus contains four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. A key factor in the virulence of COVID-19 is the interaction of the receptor-binding domain (RBD) of protein S located on the outer membrane of SARS-CoV-2 with the human transmembrane serine protease-activated receptor angiotensin-converting enzyme 2 (ACE2) [2]. The main target cells for coronaviruses are alveolar epithelial cells in whose cytoplasm the virus replicates [3]. However, ACE2 is not only expressed in type 2 lung alveolar cells but can also be detected in various human cells susceptible to viral infection, including epithelial cells of the small and large intestine [4]. Coexpression of ACE2 and TMPRSS2 is required for SARS-CoV-2 to enter cells. Within the gastrointestinal tract, coexpression of ACE2 and TMPRSS2 transcripts was highest in the small intestine and colon/rectum. More than 20% of small intestinal enterocytes and approximately 5% of colonocytes coexpress ACE2 and TMPRSS2 [5]. At present, the pathogenesis of new coronavirus infection is poorly understood [3].  

This review considers the mechanisms of intestinal cell damage by SARS-CoV-2 virus, gastrointestinal manifestations described by researchers in COVID-19 patients, a possible fecal-oral mechanism of coronavirus infection and peculiarities of its course in patients with inflammatory bowel diseases.


The following clinical variants and manifestations of COVID-19 exist and have been described: asymptomatic; mild (with lesions of the upper airways only); moderate (pneumonia without respiratory failure); severe (pneumonia with the development of respiratory failure) [6]. In addition to pneumonia, COVID-19 can also cause symptoms of damage to other organs and systems, including digestive organs. According to studies, digestive system manifestations include: loss of appetite (39.9% to 50.2%), diarrhea (2.0% to 49.5%), nausea (1.0% to 29.4%), vomiting (3.6% to 15.9%), abdominal pain (2.2% to 6.0) and gastrointestinal bleeding (4.0%) in severe cases [7]. There are also publications about damage to the liver [8] and pancreas in COVID-19 [9].  At the same time, researchers note that gastrointestinal symptoms were more common in severe cases of COVID-19 (23%) than in mild cases of infection (8%) [10].   

A study by scientists at the Hubrecht Institute found that the SARS-CoV-2 coronavirus that causes COVID-19 can infect and multiply in intestinal cells. Using modern human intestinal cell culture models, the scientists successfully replicated the virus in vitro and monitored cell response to the virus, providing a new cell culture model for studying COVID-19.  The researchers used human intestinal organoids, a "mini intestine" cultured in a cup, and demonstrated that SARS-CoV-2 readily replicates in enterocytes, resulting in the production of large numbers of infectious viral particles in the gut (Figure 1).  Intestinal symptoms of SARS-CoV-2 can be associated with damage to enterocytes expressing ACE2 and are accompanied by inflammation or intestinal damage. Loss of intestinal barrier integrity occurs and intestinal microbes, which can activate innate and adaptive immune cells to release proinflammatory cytokines, enter the circulatory system, leading to systemic inflammation [12]. These findings suggest that the digestive system, along with the respiratory tract, may be a potential pathway for SARS-CoV-2 infection, and may explain why some patients experience gastrointestinal symptoms [13].  

Some studies have reported an increased incidence of diarrhea in patients with coronavirus infection.  Clinical studies show that the incidence of diarrhea ranges from 2% to 50% of cases [14]. For example, in a study of 204 patients with COVID-19 in Hubei province, 103 (50.5%) patients were found to present with digestive symptoms, including lack of appetite, diarrhea, vomiting, and abdominal pain [15]. In another study of a group of 95 patients with severe acute respiratory syndrome, 58 had gastrointestinal symptoms, with diarrhea (24.2%), anorexia (17.9%), and nausea (17.9%) being the main symptoms [16]. In one meta-analysis involving 4805 patients with COVID-19, the pooled rates were 7.4% of patients reporting diarrhea and 4.6% of patients reporting nausea or vomiting [17].  If lack of appetite is excluded from the analyses (because it is less gastrointestinal specific), we can conclude that diarrhea is the most frequent complaint among gastrointestinal symptoms.  

Diarrhea associated with COVID-19 most often occurred 1-8 days after onset, and the average duration was 3 days. In some patients, diarrhea was the first symptom and lasted 1-14 days, with 34.3% of diarrhea appearing watery [7]. That is, diarrhea may precede or follow respiratory symptoms [14]. A case has been described of a 22-year-old patient hospitalized with only diarrhea and fever on admission, who was later diagnosed with bilateral pneumonia and had SARS-CoV-2 RNA in a nasopharyngeal swab [18]. Due to the fact that there is a discrepancy in the data and given that some authors draw attention to a possible association of diarrhea with antibiotic intake, more research is needed to identify the percentage of patients with COVID-19 and intestinal symptoms.  

Studies have also shown that RNA of the virus is detected in the feces of COVID-19 patients, hence the possibility of fecal-oral transmission of COVID-19 infection (not currently proven).  COVID-19 RNA was first isolated in feces on day 7 of illness in a 35-year-old US patient in 2019 who was admitted with complaints of nausea, vomiting, and subsequent diarrhea [19]. Somewhat later, a case of COVID-19 was published with a positive result for viral nucleic acid in a fecal sample and negative results on several pharyngeal and sputum samples in a 25-year-old patient with respiratory signs of the disease [20]. At the same time, there is evidence that patients with a positive stool sample did not experience gastrointestinal symptoms [21]. It should be noted that the duration of positive stool results ranges from 1 to 12 days, and viral RNA in stool can remain positive even after negative respiratory test results (23.29%) [22].  

Some patients with COVID-19 have been found to have microbial gut dysbiosis with reduced probiotics such as Lactobacillus and Bifidobacterium. This is because ACE2 regulates intestinal amino acid homeostasis, antimicrobial peptide expression, and the ecology of the gut microbiome. ACE2 deficiency leads to a significant change in the composition of the gut microbiota due to a decrease in the production of antimicrobial peptides that control the gut microbial community. It can be concluded that the microbiota plays a crucial role in gut homeostasis, and changes in its composition and functional activity are involved in local inflammation [23]. 

Patients with chronic inflammatory bowel disease and COVID-19 deserve special attention. Patients with inflammatory bowel disease may be at increased risk for SARS-CoV-2 infection, and the risk of a severe clinical course of COVID-19 may be increased in individuals with VIC receiving immunomodulatory treatment [24]. According to data in the SECURE-IBD registry as of March 23, 2020, 40 cases of COVID-19 have been reported worldwide in patients with VHD, including two deaths [4]. For example, a fatal case was described of an 80-year-old patient admitted to the department with an exacerbation of left-sided ulcerative colitis, which she had been suffering from for 3 years. Corticosteroid therapy was prescribed, which significantly improved the patient's condition, but on the 4th day the patient developed fever up to 39°C and a dry cough. Computed tomography of the chest organs confirmed bilateral pneumonia, and SARS-CoV-2 RNA was detected in a nasopharyngeal swab. Despite antiviral and corticosteroid therapy and respiratory support, the patient died on the 14th day after admission [25]. 

The official website of the Crohn's and Colitis foundation has published guidelines for patients with IBD that recommend continued treatment of IBD with aminosalicylates, antibiotics, and biologics, except for steroids, which can suppress the immune system [26]. Currently, it does not seem reasonable to recommend discontinuation of immunosuppressant treatment in patients with IBD [27]. Patients taking immunosuppressants and biologics are advised not to travel or gather in large groups.  Research on the relationship between COVID-19 and chronic inflammatory bowel disease is still ongoing, and physicians and scientists are constantly reviewing new information and revising recommendations [28].


Therefore, according to the analysis of the sources available to us today, the probability of fecal-oral transmission and the prevention of the spread of infection remain insufficiently studied. The question of the relationship between COVID-19 and the microbiome also remains relevant, since knowledge in this area will allow us in the future to develop new approaches in the treatment of infection targeting different components of the gut microbiota. To date, there is also no specific therapy for COVID-19, including SARS-CoV-2-associated diarrhea, except for symptomatic and maintenance therapy.      All this indicates the need for further research on intestinal lesions developing in coronavirus infection (COVID-19), studying their impact on the course and prognosis of the disease.


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