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14 May 2020
SARS-CoV-2, the viral strain implicated in COVID-19 (Coronavirus Disease 2019), is known to infect human lung cells via respiratory transmission. The presence of respiratory symptoms are key features of infection. However, it has been demonstrated that transmission of SARS-CoV-2 may also be transmitted via a faecal-oral route and cause gastrointestinal infection.
Swabs of the nasopharynx are used to detect the presence of SARS-CoV-2 RNA, as the upper respiratory tract is the main site of viral replication. Although a flu-like illness with fever and cough are the most prominent symptoms in SARS-CoV-2 infection, it is not uncommon for individuals to experience concurrent gastrointestinal symptoms such as nausea and diarrhoea1. Furthermore, viral SARS-CoV-2 RNA has been detected in faecal samples of a subset of patients infected2, whilst being absent in nasopharyngeal testing3. It is reasonable therefore to think that the respiratory tract may not be the only site of replication. This has been confirmed by Lamers et al, researchers in virology and molecular medicine in the Netherlands who recently demonstrated that SARS-CoV-2 can infect enterocytes (gut cells) in a human organoid model4. COVID-19 can therefore be said to be transmitted to and infect gut cells rather than being localised only to the respiratory system.
Organoids are developed from adult stem cells and used as a model of the organ from which they are derived as they encompass key features of this organ. In this study, Lamers et al utilised hSIOs (human Small Intestinal Organoids) from primary gut epithelial stem cells which contained enterocytes, goblet cells and enteroendocrine cells to simulate the small intestine cellular environment. These organoids were incubated with SARS-CoV-2. Following application of qRT-PCR 60 hours into incubation, a laboratory technique which allows detection and quantification of SARS-CoV-2 RNA, a significant increase was noted of the viral RNA titre. These findings indicated infection of the organoids with SARS-CoV-2. Furthermore, following infection with SARS-CoV-2, the virus induced genetic changes increasing the expression of cytokines (glossary definition, in the Probiotics Learning Lab: cytokines), antiviral type 1 and type 3 interferons and interferon stimulated genes. SARS-CoV-2 was demonstrated to successfully infect the small intestinal enterocyte model, indicating an ability to infect human gut cells.
The spike protein of SARS-CoV-2 is a membrane protein which binds to the receptor Angiotensin Converting Enzyme-2 (ACE-2) on human cells. Through binding of a virus spike protein with a human cell, fusion of the virus and human cell is enabled to occur, which allows the virus to enter and infect the cell. In the respiratory tract, ACE-2 is expressed by alveolar epithelial type 2 cells and ciliated cells. It is through these respiratory cells that SARS-CoV-2 infects the human host. Interestingly, in the human body, ACE-2 is expressed in the highest concentration in the gut on the brush border of intestinal enterocytes. ACE-2 was detected on the organoid enterocytes and it was through these receptors SARS-CoV-2 gained entry. In brief, SARS-CoV-2 infects gut cells through the ACE-2 receptors, the same way that it infects cells of the respiratory system.
Given the evidence suggesting a faecal-oral transmission route of SARS-CoV-2, thorough hand washing is more important now than ever, along with regular disinfecting of potentially contaminated surroundings. Although gastrointestinal symptoms have been only reported concurrently with respiratory symptoms thus far1, it is important to be aware that these symptoms, including nausea and diarrhoea, are part of the clinical picture of COVID-19 infection. We already know that maintaining a healthy gut, and in turn a healthy gut microbiome, is an important aspect of general immune health, as more than 70% of our immune cells are located in the gut. This latest evidence suggests that gut health could be a key consideration in the management of this intriguing new virus.
1. Cholankeril G, Podboy A, Aivaliotis VI, et al. High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California. Gastroenterology. 2020. doi:10.1053/j.gastro.2020.04.008
2. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA - J Am Med Assoc. 2020. doi:10.1001/jama.2020.3786
3. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831-1833.e3. doi:10.1053/j.gastro.2020.02.055
4. Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science (80- ). May 2020:eabc1669. doi:10.1126/science.abc1669