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The CoronaVirus News

January 29, 2023 8:58 pm

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COVID-19 and GI Symptoms


COVID-19 was initially considered a respiratory disease, but the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to serious systemic consequences affecting major organs including the digestive system.1,2 Gastrointestinal (GI) symptoms such as diarrhea, loss of appetite, or nausea are common and can have many causes, so experiencing any of these doesn’t mean you have COVID-19. However, they can sometimes be early warning signs and often, but not always, accompany the usual symptoms of a COVID-19 infection. Although the information varies, as many as 50% of the hospitalized adults with COVID-19 reported at least one gastrointestinal symptom such as nausea, vomiting, abdominal pain, or diarrhea with variable onset and severity.1,2,3 Also, nearly a quarter of the children infected with the virus displayed GI symptoms.4 The majority of these are mild and resolve without requiring medical treatment.1,2 Nevertheless, it is clear that SARS-CoV-2 infects the GI tract. Typically, patients who have GI symptoms will also have the more common upper respiratory symptoms, such as a dry cough, fever, sore throat, or difficulty breathing. Sometimes, the GI symptoms will come first, and the respiratory ones will follow a day or so later.1,2 Interestingly, in about 20% of the cases, individuals with COVID-19 only exhibited GI related symptoms. Patients with digestive symptoms also had longer duration between onset of symptoms and viral clearance and were more likely to have a virus positive stool test.1,2,3

Symptoms common in both COVID-19 and seasonal flu include nausea, cough, fever, and fatigue.1,2,5 One of the major differences is that COVID-19 often leads to the loss of taste or smell, which is rare with the common flu.5 The transient loss of taste or smell is related to the virus infecting the cells that line our mouth through the receptor called angiotensin converting enzyme 2 (ACE2).1,3 Vomiting is also a more common symptom in COVID-19 compared to seasonal flu.

Does COVID-19 Transmit Through the Stool?

In the initial stages of the pandemic, there were worries about fecal-oral transmission of the disease since the genetic materials of the virus and actual live virus were found in the feces from infected patients.1 In some cases, the viral genetic materials were detected in the stool regardless of the gastrointestinal symptoms, as well as in feces after a negative nasal test.1,6 These observations suggest that the SARS-CoV-2 may actively infect and replicate in the GI tract. Despite these findings, scientists do not believe that fecal-oral transmission is a major route for the virus.6

How does COVID-19 Affect the GI Tract?

COVID-19 impacts and disrupts the GI system and affects the body in two primary ways. The first effect is that SARS-CoV-2 attacks the body by interacting with a receptor called angiotensin converting enzyme 2 (ACE2),1,3,7 which is present in many organs. They are common on the cells that line our body surfaces, such as the respiratory tract and especially the GI tract, where they are most prevalent.7,8 SARS-CoV-2 binds to ACE2 to facilitate its entry into epithelial cells. The virus enters epithelial cells by way of the spike protein on the viral coat, which is primed by the cellular transmembrane serine protease 2 (TMPRSS-2). This interaction may disrupt the barrier function by altering the role of various barrier proteins, such as ZO-1, occluding, and claudins,3,7 which may lead to virus-induced diarrhea. The disruption in barrier integrity might increase intestinal permeability, which then allows bacterial products and toxins into the circulatory system, further worsening the systemic inflammatory response. The resulting inflammation leads to the recruitment and activation of immune cells that could lead to a cytokine storm and organ failure.

SARS-CoV-2 binds to ACE2 receptors and then enters our organs, causing damage. In the GI tract, it affects the intestinal lining, leading to diarrhea, stomach upset, vomiting, and inflammation.9 Severe cases may even lead to obstructions, co-infections, or intestinal necrosis and organ failure.10

The other way COVID-19 affects the GI tract is by modifying the microbiome.10,11 Our gut microbiome is composed of trillions of bacteria and other microorganisms that help with metabolism, digestion, fighting infection, and mood regulation. Damage to the gut microbiome can lead to opportunistic infections, severe GI symptoms (pain, nausea, diarrhea), and even anxiety and depression.12

A study done in Hong Kong characterised the gut microbiome alterations in COVID-19.13 Infection led to a decrease in microbiome diversity (e.g., Faecalibacterium prausnitziiLachnospiraceae bacteriumEubacterium rectaleRuminococcus obeum, and Dorea formicigenerans), an increase in opportunistic pathogens (e.g., Clostridium hathewayiActinomyces viscosus, and Bacteriodes nordii), and a decrease in beneficial commensals. A six-month follow up study on patients with COVID-19 showed significant decreases in the richness of the gut microbiome across the acute, convalescence, and post-convalescence phases of the infection.9

Other studies have had similar findings and have linked the negative effects on gut bacteria to severe disease, opportunistic infections, and even symptoms of ‘long COVID’ (also known as post-acute sequelae of COVID-19).9,10 Studies are ongoing to determine whether any probiotics may be of benefit to prevent or reduce symptoms of COVID-19 infection.

COVID-19 and IBD

In the early stage of the pandemic, an international collaborative, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) database, came together to monitor outcomes of COVID-19 in IBD patients worldwide.2 Through this, many important findings have been made. Inflammatory bowel disease (IBD) patients are often on injectable immunosuppressants which may make them more susceptible to disease and infection.2 However, the database found that patients on potent immunosuppressants, such as the class of drug called TNF-alpha inhibitors (e.g., infliximab, adalimumab, and certolizumab), do not have to worry about an increase in infection risk.2 They also found that prevention is key.

Overall, there is currently no evidence for an increased risk or aggravated outcomes in patients with IBD11 and the prevalence is not higher in these patients as compared to the general population. However, patients that are having an acute flare of IBD may need to take more potent immunosuppressants. In that heightened state of inflammation and immune suppression, there is a higher risk for COVID-19 infection and severe outcomes.2

Evidence on the potential impacts of COVID-19 on chronic inflammatory conditions, such as IBD, continues to evolve. It is best to consult your doctor about these if you are immunocompromised.

Conclusion

SARS-CoV-2 has spread exponentially as a pandemic. It primarily causes severe respiratory symptoms but also affects the GI system in many patients. The importance of gut homeostasis and appropriate immune response toward viral infection has gained momentum during the COVID-19 pandemic.

Clearly, GI involvement is an important feature in some COVID-19 patients. Over the past few years, we have gained a large amount of knowledge and insights for understanding the GI effects of SARS-CoV-2 and the underlying pathogenesis. Current studies have begun to explore the use of probiotics as therapy for COVID-19 as well as looking at microbiome markers for vaccine efficacy.

Updated: 2022-11-24
1. Kariyawasam JC et al. Gastrointestinal manifestations in COVID-19. Trans R Soc Trop Med Hyg. 2021;115(12):1362-1388.

2. Bilal M et al. Coronavirus disease-2019: implications for the gastroenterologist. Curr Opin Gastroenterol. 2021;37(1):23-29.

3. Pola A et al. COVID-19 and gastrointestinal system: A brief review. Biomed J. 2021;44(3):245-251.

4. Lo Vecchio A et al. Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome. JAMA Netw Open. 2021;4(12):e2139974.

5. Piroth L et al. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. Lancet Respir Med. 2021;9(3):251-259.

6. Moura IB et al. Can SARS-CoV-2 be transmitted via faeces? Curr Opin Gastroenterol. 2022;38(1):26-29.

7. Roy K et al. COVID-19 and gut immunomodulation. World J Gastroenterol. 2021;27(46):7925-7942.

8. Hikmet, F et al. The protein expression profile of ACE2 in human tissues. Molecular Systems Biology. (2020)16:e9610. https://doi.org/10.15252/msb.20209610.

9. Clerbaux LA et al. Mechanisms leading to gut dysbiosis in COVID-19: Current evidence and uncertainties based on adverse outcome pathways. Journal of Clinical Medicine. 2022;11(18):5400.

10. Soeselo DA et al. Bowel necrosis in patient with severe case of COVID-19. BMC Surgery. 2021;21(1).

11. Singh AK et al. Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: A systematic review and meta-analysis. United European Gastroenterol J. 2021;9(2):159-176.

12. Clapp M et al. Gut microbiota’s effect on Mental Health: The gut-brain axis. Clinics and Practice. 2017;7(4):987.

13. Yeoh YK et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70(4):698-706.
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