Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention, and Management

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

Keywords: ACE2; Angiotensin-Converting Enzyme 2; COVID-19; Diarrhea; Epidemiology; SARS-CoV-2; TMPRSS2.

Figure 1

Proposed model for SARS-CoV-2-associated diarrhea. SARS-CoV uses ACE2 and the serine protease TMPRSS2 for entry in lung AT cells. ACE2 and TMPRSS2 are not only expressed in lung, but also the small intestinal epithelia. ACE2 is expressed in the upper esophagus, liver, and colon. ACE2 is also necessary for the surface expression of amino acid transporters of the small intestine. Amino acids, like tryptophan, regulate the secretion of antimicrobial peptides by Paneth cells via mTOR pathway activation. Antimicrobial peptides impact the composition and diversity of the microbiota. Disturbance of this pathway could drive inflammation (enteritis) and ultimately diarrhea. SARS-CoV-2 rendering courtesy of Centers for Disease Control and Prevention. The science cartoon was created with Servier Medical Art licensed under a Creative Commons Attribution 3.0 Unported License. AT, Alveolar Type; mTOR, mammalian target of rapamycin.