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Recent reports have suggested that gastrointestinal (GI) and hepatic manifestations of COVID-19 are more prevalent than initially noted, particularly in Western populations. To investigate this, Reem Z. Sharaiha, MD, MSc, of the division of gastroenterology and hepatology at Weill Cornell Medicine and NewYork-Presbyterian Hospital in the pandemic's U.S. hot spot, New York City, and colleagues conducted a retrospective review of 1,059 adult cases of confirmed COVID-19 during the period March 4 to April 9.

Published in the analysis revealed that 22% of presenting patients had diarrhea, 7% had abdominal pain, and 16% and 9% had nausea and vomiting, respectively. In all, 33% of patients had at least one GI manifestation, and 62% of patients had biochemical evidence of liver injury, with at least one elevated liver enzyme.

Interestingly, GI symptoms were associated with lower rates of death (8.5% vs 16.5% with no GI symptoms), and a lower risk of the composite of death and ICU admission (28% vs 38%).

Sharaiha discussed the findings in the following interview.

Were you prompted by clinical experience in New York patients or by other studies pointing to digestive tract manifestations of COVID-19?

Sharaiha: I was prompted by other studies. While there were a lot of data coming from China, there was not a single study from the West that focused on GI symptoms alone. We had the advantage of hindsight, so we knew what symptoms to look for, and when we reached our COVID-19 peak in New York City, we had enough patients to report on GI manifestations and their clinical implications in a meaningful way.

What were the most serious GI and hepatic manifestations of COVID-19 infection observed and what association did such symptoms have with eventual clinical outcomes?

Sharaiha: The most common symptom was diarrhea. Other GI symptoms included anorexia, abnormal liver function tests, nausea, vomiting, and loss of either taste or smell. If you had diarrhea as your most prominent symptom, you were more likely to have a better disease course. On the flip side, if you had abnormal liver tests, that would signify a worse outcome, meaning admission to intensive care or death.

Were any subgroups of patients more affected by GI-hepatic manifestations?

Sharaiha: Female patients were 30% more likely to present with GI symptoms, and those with chronic liver disease were more than twice as likely, but only older age was significantly associated with higher rates of liver test abnormalities at presentation.

Did any counterintuitive or surprising findings emerge?

Sharaiha: In the presence and severity of digestive symptoms on initial presentation correlated with worsening disease severity. And in our study, though diarrhea meant a better clinical outcome, affected patients were more likely to be admitted to hospital. That may have been a function of their being dehydrated or our not knowing how to prognosticate those with diarrhea.

Has there been speculation as to how this virus might readily attack the digestive tract?

Sharaiha: There might be a potential explanation for the relatively high prevalence of diarrhea and the risk of small bowel involvement with SARS-CoV-2 compared with other GI symptoms, since SARS-CoV-2 is thought to have an affinity for the angiotensin-converting enzyme 2 (ACE2) receptor, potentially permitting virus entry into cells. Ileal epithelial cells have a significantly high ACE2 expression, while cholangiocytes and esophageal epithelial cells also express this receptor as a potential target for the virus.

Were the GI symptoms more serious in some patients than the more usual respiratory symptoms?

Sharaiha: It is hard to tease that out in a retrospective study, but in some patients, if the diarrhea was bad enough for admission, that may have resulted in dehydration, electrolyte abnormalities, and/or colitis.

Will these findings help clinicians to better manage the treatment of patients presenting with presumed COVID-19 infection or expand the current indications for testing in any way?

Sharaiha: A small proportion, as far as we can tell, may only present with GI manifestations. So a high index of suspicion with any unexplained symptoms and testing should now be part of the algorithm for any GI manifestations -- polymerase chain reaction, serology, or even stool. These results help clarify the diagnosis of patients with COVID-19 and can be considered in risk stratification.

Looking ahead, what would be most helpful to clinicians?

Sharaiha: I think more collaborative data are important, especially to understand the extent of disease and how it affects outcomes and prognosis.

You can read the abstract of the study here, and about the clinical implications of the study here.