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UPDATED March 19, 2020: This story has been updated to clarify the study findings. // Patients with gastrointestinal (GI) symptoms who were admitted to the hospital and were diagnosed with COVID-19 were more likely to have severe disease than patients who did not have GI symptoms, according to findings published March 18 in the American Journal of Gastroenterology.

However, the unexpectedly large proportion is due in part to the inclusion of anorexia, said Brennan M. R. Spiegel, MD, MSHS, co–editor-in-chief of the American Journal of Gastroenterology.

"If you leave out anorexia, which is very nonspecific, the percentage of COVID-19 patients with GI symptoms is about 30%," Spiegel told Medscape Medical News.

Lei Pan, MD, PhD, of Binzhou Medical University Hospital in Binzhou, China, and colleagues in the Wuhan Medical Treatment Expert Group conducted a descriptive, cross-sectional, multicenter study on 204 patients who had polymerase chain reaction–confirmed COVID-19 at three hospitals in Hubei province from January 18, 2020, to February 28, 2020. The team considered clinical characteristics, laboratory data, and treatment.

Ninety-nine patients (48.5%) presented to the hospital with digestive symptoms as their chief complaint. Most of these patients did not have underlying digestive diseases. Their symptoms included anorexia (83.8%), diarrhea (29.3%), vomiting (0.8%), and abdominal pain (0.4%).

Like Spiegel, David A. Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine in Norfolk, says that the patients with anorexia should be excluded. A more realistic ― if high ― estimate is the 29% who presented with diarrhea, Johnson says.

"Other GI problems ― abdominal pain, nausea, and vomiting ― may raise the percentage slightly from the 29%," Johnson said.

For the overall study population, Pan and colleagues found that the average time from symptom onset to hospital admission was 8.1 days. However, it was 9.0 days for patients with GI symptoms, including those with anorexia, compared with 7.3 days for those who did not have digestive symptoms. Seven patients had digestive symptoms but no respiratory symptoms at admission.

Digestive symptoms appeared to be tied to worse outcomes. Whereas 60% of patients without digestive symptoms recovered and were discharged, only 34.3% of the patients with digestive symptoms recovered.

Spiegel explained how the digestive symptoms arise. "The virus enters human cells through the ACE2 receptor in the lungs but also in other body parts, including the GI tract. We think the virus gets into saliva and we swallow it, and then it passes through the acid layer in some patients and uses the ACE2 receptors to enter epithelial cells that line the intestine."

The virus replicates rapidly in the cells of the GI lining, enters the intestinal tract, and is shed, Spiegel said. "There is clear evidence from endoscopy that it can damage the stomach and the intestines. The fact that these patients do worse may be that more of the body is involved."

An explanation for the longer time between symptom onset and COVID-19 diagnosis might be that patients with only GI symptoms or mild respiratory complaints did not think that they could have the coronavirus.

"When the patients were admitted to the hospital, no one yet knew they had COVID-19. Almost half, when asked why they were there, mentioned a digestive problem. They may have also had a respiratory symptom, like a cough or shortness of breath, but that's not what they said was their main complaint," Spiegel told Medscape Medical News.

The authors conclude, "Clinicians should recognize that digestive symptoms, such as diarrhea, may be a presenting feature of COVID-19, and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms rather than waiting for respiratory symptoms to emerge."

Spiegel points out that the Centers for Disease Control and Prevention has yet to include GI symptoms in their guidance, although recommendations are changing rapidly.

Spiegel urges caution in evaluating patients with only GI symptoms. "A large part of the population has diarrhea, abdominal pain, nausea, and vomiting regularly, so it's clearly impossible and irresponsible to start testing everyone with diarrhea for COVID-19. But if somebody has new fever and diarrhea and suspects they may have had contact with a patient or carrier, I'd want to test them."

Limitations of the study include a relatively small sample, the retrospective design, and not testing for SARS-CoV-2 RNA in stool.

Am J Gastroenterol. Published online March 18, 2020. Full text

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