By David Wild

Should COVID-19 patients undergo routine fecal testing? What’s the best management approach for those with diarrhea, nausea and vomiting? As emerging data point to gastrointestinal (GI) symptoms as part of the clinical picture of COVID-19, physicians are grappling with how best to approach patients presenting with these clinical symptoms.

Noha Eltoukhy, PharmD, an antimicrobial stewardship program coordinator and a clinical pharmacy specialist in infectious diseases, St. Mary Medical Center, Langhorne, Pa., said she has noticed several of her hospital’s COVID-19 patients either reporting diarrhea before admission or presenting with the symptom. While patients who present with this symptom undergo testing for “the usual” pathogenic culprits, such as Clostridioides difficile and norovirus, their stool is not tested for SARS-CoV-2.

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“In terms of managing COVID-19 patients with diarrhea, we don’t specifically target the diarrhea unless we know it's caused by a pathogen we can treat,” she said, noting she believes the strict isolation and use of personal protective equipment employed for COVID-19 patients limits potential fecal–oral transmission.SARS-CoV-2 is thought to make its way into the GI tract by adhering its spike proteins to angiotensin-converting enzyme 2 receptors, which are located in the lungs but also widely present in the GI tract. 

A growing number of publications are shedding light on the frequency and nature of the GI symptoms of COVID-19. One study of 71 patients at a single institution in China found more than 53% of patients had SARS-CoV-2 RNA in their stool upon polymerase chain reaction testing, and the pathogen was found in the stool of 23% of patients who did not have the pathogen in respiratory samples (Gastroenterology 2020 Mar 3. [Epub ahead of print]. doi.org/10.1053/j.gastro.2020.02.055).

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More recently, an analysis from Wuhan, China, where the pandemic began, included 206 consecutive patients with mild COVID-19 and found “indirect support of possible fecal transmission” (Am J Gastroenterol 2020 Mar 30 [Epub ahead of print]). The study reported that 23% of patients presented with diarrhea, nausea or vomiting; 34% had both digestive and respiratory symptoms; and the remainder had only respiratory symptoms. Diarrhea was the most common GI manifestation of COVID-19 and the first symptom of COVID-19 in 19% of patients. It lasted an average of 5.4 days (±3.1 days) with a frequency of 4.3 (±2.2) bowel movements per day. Those with digestive symptoms were more likely to have SARS-CoV-2 RNA in their fecal samples than those with respiratory symptoms alone (73.3% vs. 14.3%; P=0.033).

Of note, more than 38% of patients with a GI symptom did not present with fever, which is considered a cardinal symptom of COVID-19.

The study also indicated that patients with digestive symptoms sought care 16 days after symptom onset, compared with 11.6 days for those with respiratory symptoms alone (P<0.001). Additionally, the time between symptom onset and viral clearance was significantly longer for those with digestive symptoms.
“The longer disease course in patients with digestive symptoms might reflect a higher viral burden in these patients in comparison to those with only respiratory symptoms,” the authors speculated.

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While the researchers urged routine testing of both respiratory and fecal samples for suspected COVID-19 patients and encouraged that patients with new-onset diarrhea during this pandemic should be suspected of having this illness, until there is clear evidence that targeting the GI symptoms of COVID-19 has an effect on the course of the disease, scientists like Sumit Chanda, PhD, the director and a professor, immunity and pathogenesis program, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, Calif., are focusing their energy on the respiratory tract.

“Most people are dying from these respiratory-type pneumonias, and it doesn’t seem—other than the shedding—that there’s a big clinical impact of the virus replicating in the GI [tract],” Dr. Chanda said during a Newswise press briefing on April 2.

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For those considering management of diarrhea, nausea and vomiting in COVID-19 patients, Maria Luisa Alcaide, MD, an associate professor of infectious diseases at University of Miami Miller School of Medicine, believes agents like ondansetron, metoclopramide, loperamide and antacid agents, such as proton pump inhibitors and H2 inhibitors, are safe to use.

However, she cautioned that patients receiving hydroxychloroquine for COVID-19 are at a higher risk for QT prolongation with concurrent ondansetron or loperamide administration.

“In general, our approach is simply to ensure adequate hydration,” Dr. Alcaide said.

Like other clinicians, she is waiting for additional data clarifying whether the presence of SARS-CoV-2 in the GI tract, and the fecal viral shedding that can occur with COVID-19, in fact translates to fecal–oral transmission.

“Shedding in the GI tract doesn’t mean there’s transmissible virus in the stool. We’re learning all about this as we go, and it is critical that we stay updated with new information regarding implications of COVID-19 manifestations in the GI tract,” she said.