Diarrhea is a frequent symptom in patients infected with SARS-CoV-2, researchers report in articles published in Clinical Gastroenterology and Hepatology. Researchers propose suspecting COVID-19 in any patient with diarrhea, even in the absence of respiratory symptoms, and taking appropriate precautions and approaching endoscopy as a procedure with high risk of transmission.
A systematic review by Ferdinando D’Amico et al investigated the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. The authors found incidence rates of diarrhea ranging from 2% to 50% of cases, with diarrhea preceding or following fever and respiratory symptoms. A pooled analysis revealed that overall, 10.4% of patients with COVID-19 have diarrhea.
SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) to attach to the cell membrane and the serine protease TMPRSS2 to fuse with it (see figure). ACE2 and TMPRSS2 are expressed not only in lung, but also in the small intestinal epithelia; ACE2 is expressed in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity for ACE2 is significantly higher (10- to 20-fold) than that of SARS-CoV.
There have been reports of SARS-CoV-2 RNA in stool, detectable for longer time periods than virus RNA in nasopharyngeal swabs. There is also evidence for fecal to oral transmission.
D’Amico et al discuss the epidemiology of COVID-19-associated diarrhea; they report from an analysis of pooled data from available studies that overall, 10.4% in patients with COVID-19 have diarrhea.
The authors also studied characteristics of COVID-19-associated diarrhea, which ranged from 2 to 8 days, and reported that a higher proportion of patients with severe disease had diarrhea. Patients with diarrhea, nausea, and vomiting were more likely to require mechanical ventilation and had acute respiratory distress syndrome compared with patients without gastrointestinal symptoms. Interestingly, diarrhea was reported in about 20% of patients with SARS in Hong Kong in 2003, and up to 33% of patients with MERS. Some studies also associated diarrhea with worse outcomes of patients with SARS. D’Amico et al propose that all candidates for fecal microbiota transplantation be screened for the virus.
In a Here and Now: Clinical Practice article, Olga C. Aroniadis et al discuss the gastrointestinal effects of COVID-19, including diarrhea, anorexia, abdominal pain, nausea, vomiting, dysgeusia, and bloody diarrhea. Furthermore, 15%–50% of patients have abnormal results from liver function tests, and 17% were reported to have increased serum levels of pancreatic enzymes.
The authors discuss whether the effects of COVID-19 on the intestine, liver and pancreas are caused directly by the virus (as was believed to be the case for 2003 SARS and MERS) or result from the inflammation. It is important to determine whether SARS-nCoV-2 induces a systemic inflammatory response through gut epithelial pathways.
Aroniadis et al state that shedding of SARS-nCoV-2 in the stool also deserves further research, because the presence of RNA does not necessarily indicate virus viability or infectivity. Beyond the need for heightened precautions in the handling of stool samples, cleaning of hospital rooms and endoscopy suites, and flushing of toilets, we need to increase our understanding of the infectivity of stool and determine the risk of food-borne illness.
Studies are also needed to determine whether the virus causes long-term damage to the gut and increases risk for irritable bowel syndrome or gastroparesis. Aroniadis et al ask about use of immunosuppressive medications for patients with liver transplants or inflammatory bowel diseases, and how can we re-expand endoscopy services to best serve our patients without putting them and ourselves at risk.
To help answer these questions, gastroenterologists and hepatologists should contribute local and national research initiatives. The North American Alliance for the Study of Digestive Manifestations of COVID-19 is seeking additional centers; the process for contributing is provided on GI-COVID19.org. Other registries evaluating COVID-19 in patients with IBD or cirrhosis can be accessed at covidibd.org and covidcirrhosis.web.unc.edu.