COVID Long-Haulers: Gastrointestinal System 

Courtesy of Tint Tha Ra Wun 


The coronavirus diseases of 2019 or COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease, which started in Wuhan, China in late 2019, has become a global pandemic, with over 180 million cases and 3.9 million deaths worldwide.


Today, a wide range of research has been conducted to study the symptoms as well as the complications of COVID-19. Although acute COVID-19 illness typically lasts two to six weeks, some patients have reported debilitating symptoms persisting or recurrent for weeks or months after the acute illness has ended (Dwivedi, 2021). In a living systematic review on the Prevalence of Post-COVID-19 Conditions by Canadian researchers, they have found that 83% of the individuals reported persistence or presence of one or more short-term symptoms and 56% reported long-term symptoms. The most common symptoms in both periods include fatigue, general pain or discomfort, sleep disturbances, shortness of breath, and anxiety or depression. 


In this article, we would like to explore the long-term gastrointestinal effects of COVID-19. The gastrointestinal system is one of the 11 organ systems in the human body. It is mainly responsible for breaking down food into nutrients, playing a crucial role in maintaining energy homeostasis. 


There is evidence that SARS-CoV-2 may be present in the gastrointestinal tract and that the angiotensin-converting enzyme 2 (ACE2) receptor is highly expressed throughout the gastrointestinal tract. Thus, SARS-CoV-2 may enter gastrointestinal cells via ACE2 receptors to cause direct damage to the gastrointestinal organs (Kaafarani, 2021). Moreover, different studies have investigated that SARS-CoV-2 has been observed in the colonic tissues and faeces of patients with COVID-19 (Weng et al., 2021).


Anatomy of the Gastrointestinal System 

The gastrointestinal is responsible for taking in food and liquids and breaking them down into smaller molecules that the body can absorb to use for energy, growth, and repair. 


The digestive tract, which begins at the mouth and ends at the anus, includes the mouth, pharynx (throat), esophagus, stomach, small intestine, large intestine, rectum, and anus. The accessory organs for the system include the salivary glands, liver, gallbladder, and pancreas. They produce digestive juices and enzymes necessary for the absorption of food and liquids by the body. Together, the digestive tract and the accessory organs are known as the gastrointestinal or digestive system. 

Figure. Anatomy of Gastrointestinal System 


Gastrointestinal symptoms of COVID-19

The COVID-19 mainly affects the respiratory system and the cells lining your airway. A fever, dry cough, and shortness of breath are the hallmark signs of COVID-19 (Nazario, 2020). However, this does not necessarily mean that other body systems are not destroyed by COVID-19. 


Some of the unusual symptoms of COVID-19 include gastrointestinal symptoms, such as nausea, vomiting, or diarrhea - either alone or with other COVID-19 symptoms. These symptoms sometimes develop before a fever and respiratory systems (Marshall, 2021). Up to one-third of COVID-19 patients present with gastrointestinal complaints. 


In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7) (Cheung et al., 2020). 


Another systematic review, which included 43 studies with 18,246 patients, found out that diarrhea was the most common GI symptom, affecting 11.5% of the patients. Nausea and vomiting was second most common with 6.3% and abdominal pain in third place with 2.3%. With regard to clinical severity, 17.5% of the patients were classified as severely ill, whereas 9.8% of them were considered to have a non-severe disease (Silva et al., 2020).


Gastrointestinal Complications of COVID-19 

Patients with severe COVID-19 are at particularly high risk for developing gastrointestinal complications. Some of these complications include acute liver injury and elevated transaminases, acute cholecystitis, acute pancreatitis, ileus and feeding intolerance, acute colonic pseudo-obstruction, and mesenteric ischemia. 


Nearly two-thirds of patients with severe COVID-19 develop elevated liver transaminases (Zhao et al., 2021), with reported mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) above 400 units per liter of serum (Kaafarani et al., 2020). 


Acute cholecystitis has been widely reported in patients with COVID-19, especially those who are critically ill. In most patients, the cholecystitis is acalculous, and the etiology remains largely unclear) (Kaafarani, 2021). 


Acute pancreatitis has also been widely reported in patients with COVID-19, especially in those with critical illness. However, the association between COVID-19 and acute pancreatitis is still not very well understood (Kaafarani, 2021). 


In critically ill COVID-19 patients admitted to the intensive care unit (ICU), significant Ileus and feeding intolerance occur in 46 to 53 percent (Kaafarani et al., 2020). 


Several cohort studies and case reports have reported a distinct colonic syndrome in the critically ill COVID-19 patient characterized by severe gaseous distention with no obvious distal obstruction, similar to the well-described acute colonic pseudo-obstruction, or Ogilvie's syndrome (Kaafarani, 2021). 


The most serious gastrointestinal complication reported in critically ill COVID-19 patients is mesenteric ischemia. In cohort studies of critically ill COVID-19 patients admitted to a single institution, the incidence was reported at 3.8 to 4 percent. The mortality rate of COVID-19 patients who develop mesenteric ischemia is currently reported to be as high as 40 percent, with more than 92 percent of the deaths occurring within the immediate postoperative days due to multiorgan failure or refractory septic shock (Kaafarani, 2021). 


Long term Gastrointestinal Effects of COVID-19

In one study, Weng and colleagues examined the long-term gastrointestinal sequelae of SARS-CoV-2 infections in patients admitted for COVID-19 to 12 hospitals in the Hubei and Guangdong provinces, China, between Jan 16 and March 7, 2020, and subsequently discharged. 


Gastrointestinal sequelae were defined as gastrointestinal symptoms that presented after discharge but were not present within the month before the onset of COVID-19 (Weng et al., 2021). 


This study included 117 patients with COVID-19 who had been discharged, completed one return visit (usually one month after discharge), and a telephone interview around 90 days after discharge. 52 (44%) of 117 patients reported gastrointestinal symptoms after discharge at the 90 day telephone interview, of whom 51 patients had gastrointestinal symptoms at 90 days after discharge, and one had gastrointestinal sequelae that had resolved by the 90-day follow-up (Weng et al., 2021). 


Loss of appetite was the most common gastrointestinal sequelae. 28 out of 117 patients (24%) reported this symptom at 90 days. Other gastrointestinal sequelae included nausea (21 [18%]), acid reflux (21 [18%]), and diarrhoea (17 [15%]), abdominal distension (16 [14%]), belching (12 [10%]), vomiting (11 [9%]), abdominal pain (eight [7%]), and bloody stools (two [2%]). 


The remaining 65 patients without gastrointestinal sequelae at the telephone interview did not have any gastrointestinal symptoms on admission or during hospitalisation. Whereas, of the 52 patients with gastrointestinal sequelae after discharge, 15 (29%) had gastrointestinal symptoms on admission and during hospitalisation, 34 (65%) had such symptoms during hospitalisation, and three (6%) had such symptoms only after discharge.


The percentage of 117 patients who reported gastrointestinal sequelae at the 90-day telephone interview is summarized in the bar graph below. 

Figure. The Percentage of Gastrointestinal Sequelae in 117 patients 


Limitations of this study 

The most significant limitation of this study was the unavailability of different research and adequate datasets. It was challenging to find enough data sources to conduct a full study on the long term gastrointestinal effects of COVID-19. Nevertheless, we based this research on the available systematic reviews and meta-analysis studies from reliable sources to give a general overview of the gastrointestinal long haulers of COVID-19. 



In conclusion, COVID-19 can cause unusual gastrointestinal symptoms as well as impose some long-term symptoms, including loss of appetite, nausea, acid reflux, and diarrhoea. These symptoms are common in patients 3 months after discharge from hospitalization due to COVID-19 . Moreover, patients with severe COVID-19 can develop gastrointestinal complications, such as acute cholecystitis, acute pancreatitis, ileus and feeding tolerance, acute colonic pseudo-obstruction, and mesenteric ischemia. Nevertheless, we have yet to study the frequency, severity, and treatments available for these symptoms as well as investigate other long term manifestations and complications of COVID-19 on the gastrointestinal system.   

About the Author

Tint is a pre-med Biological Sciences major student at Smith College, located in Northampton, Massachusett. She is interested in Sciences and Medicine, especially in Bioinformatics and the Cardiovascular System. Outside of school, she loves helping others and spends her free time volunteering.


Cheung, K. S., Hung , I. F. N., Chan , P. P. Y., Lung, K. C., Tso, E., Liu , R., Ng , Y. Y., Chu , M. Y., Chung , T. W. H., Tam , A. R., Yip, C. C. Y., Leung , K.-H., Fung , A. Y.-F., Zhang , R. R., Lin, Y., Cheng , H. M., Zhang , A. J. X., To, K. K. W., Chan , K.-H., … Leung, W. K. (2020, April 3). Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. PubMed . 

Dwivedi, D. R. (2021, June 10). Review of COVID-19's long-term effects. News.

Kaafarani , & Kaafarani HMA;El Moheb M;Hwabejire JO;Naar L;Christensen MA;Breen K;Gaitanidis A;Alser O;Mashbari H;Bankhead-Kendall B;Mokhtari A;Maurer L;Kapoen C;Langeveld K;El Hechi MW;Lee J;Mendoza AE;Saillant NN;Parks J;Fawley J;King DR;Fagenholz PJ;Velmahos GC; (2020, August). Gastrointestinal Complications in Critically Ill Patients With COVID-19. PubMed. 

Kaafarani , H. M. A., El Moheb, M., Hwabejire , J. O., Naar , L., Christensen , M. A., Breen, K., Gaitanidis, A., Alser, O., Mashbari, H., Bankhead-Kendall, B., Mokhtari, A., Maurer, L., Kapoen, C., Langeveld, K., Hechi, M. W. E., Lee, J., Mendoza, A. E., Saillant, N. N., Parks, J., … Velmahos, G. C. (2020, August). Gastrointestinal Complications in Critically Ill Patients With COVID-19. Pubmed . 

Kaafarani, H. M. (2021, March 24). COVID-19: Gastrointestinal symptoms and complications. UpToDate.

Marshall, W. F. (2021, March 18). Unusual symptoms of coronavirus: What are they? Mayo Clinic.

Nazario, B. (2020, April 17). Digestive Symptoms of Coronavirus (COVID-19). WebMD. 

Silva, F. A. F. da, Brito , B. B. de, Santos, M. L. C., Marques, H. S. Júnior, R. T. da S., Carvalho , L. S. de, Vieira, E. S. Oliveira, M. V., & Melo, F. F. de. (2020). COVID-19 gastrointestinal manifestations: a systematic review. Revista da Sociedade Brasileira de Medicina Tropical. 

Weng, J., Li, Y., Li, J., Shen, L., Zhu, L., Liang, Y., Lin, X., Jiao, N., Cheng, S., Huang, Y., Zou, Y., Yan, G., Zhu, R., & Lan, P. (2021, May). Gastrointestinal sequelae 90 days after discharge for COVID-19. The lancet. Gastroenterology & hepatology. 

Zhao, X., Lei , Z., Gao , F., Xie , Q., Jang, K., & Gong , J. (2021, January 29). The impact of coronavirus disease 2019 (COVID-19) on liver injury in China: A systematic review and meta-analysis. PubMed.