In late January 2020—when Covid-19, then known as 2019-nCoV, had yet to penetrate most national borders—a research paper was published in The Lancet medical journal detailing the symptoms of a cohort of 41 patients hospitalized in Wuhan, China. The study, though tiny in scale, went on to become the year’s most widely cited, and more importantly it established fever, cough, and fatigue as telltale signs of Covid-19. But it also mischaracterized one symptom as rare that we now know, in retrospect, to be common: diarrhea.
According to the study, only three percent of patients—that is, just one of the 41—reported diarrhea, while 98 percent reported fever. Personal safety guidelines released by the CDC and other public health agencies early on in the pandemic reflected back this pecking order, as did their testing policies. If someone suspected they had Covid-19 but, for example, had only diarrhea and no fever, they were refused a test. Thankfully these protocols have since been revised; as of June 2020, diarrhea, nausea, and vomiting—collectively referred to as gastrointestinal symptoms—were upgraded to the CDC’s official list of primary symptoms. In the popular imagination, however, Covid-19 is still thought of as a respiratory disease first and foremost, if not exclusively, while the pathology of the gut remains overlooked.
Understanding the full extent of how Covid-19 manifests in the human body is critical to understanding how to treat it, particularly in so-called long haulers who harbor the virus for months. Infection of the gut also has serious implications for transmission—a factor that demands consideration if we’re intent on controlling and eventually eliminating this disease once and for all.
By no strange coincidence does SARS-CoV-2, the virus that causes Covid-19, have an affinity for our ACE2 receptors. Tissues rich with ACE2 are dispersed across several of our bodily organs, from the epithelial cells lining our bronchial tubes and alveoli to the endothelial cells in our arteries and veins. Surprisingly, it isn’t in the lungs and nasopharynx where ACE2 is found in greatest abundance, but in the gut—our liver, kidneys, gallbladder, pancreas, and gastrointestinal (GI) tract.
Your skin isn’t the only part of the body exposed to the outside world. SARS-CoV-2 isn’t just breathable, but swallowable. Think of the GI tract as an elongated donut with two exterior points of entry, the mouth and anus. Stretching between them are the esophagus, stomach, and intestines. If the virus manages to get inside your mouth, it can then infect your saliva—which, like mucus and breath, SARS-CoV-2 will commandeer as a new mode of transportation, allowing it to travel deep inside the gut. With its expansive surface area and plethora of ACE2 receptors, the gut makes an ideal breeding ground not just for the virus, but other microbially inclined diseases, like inflammatory bowel disease and pneumonia.
Gut infection gives the virus more room to go forth, multiply, and shed itself through our feces. And since the early Wuhan study, many papers on gastrointestinal Covid-19 symptoms have been published that suggest as much. Two surveys released in April 2020—the first conducted in California, the second in Massachusetts—found that 32 percent and 61 percent of subjects, respectively, reported digestive symptoms. An even more reliable indicator of gut infection than presence of digestive symptoms—prevalence of viral RNA in stool—has also been observed in multiple studies. A meta-analysis of data collected around the world reported that nearly 50 percent of fecal samples taken from patients contained traces of SARS-CoV-2. For patients with severe Covid-19, the rate was nearly 70 percent. Adding to the pile of supportive evidence is a study that unleashed the virus upon intestinal organoids—experimental models of our digestive organs grown from stem cells—and found it able to colonize the epithelial tissues quite rapidly.
It might also be the case that gut infection prolongs the length of time SARS-CoV-2 remains in the body. According to one study involving about 200 Covid-19 patients with either digestive symptoms, respiratory symptoms, or a combination of the two, those who experienced gastrointestinal complications took seven to nine days longer to reach viral clearance than those who didn’t. Another study shows that in general, fecal samples taken from Covid-19 patients continue to test PCR-positive even after nasopharyngeal samples start testing negative, which is why China implemented an anal swab testing policy for incoming travelers. If the virus that lingers on in patient stool is live and infectious, that opens up fecal-oral or fecal-aerosol routes of transmission. As I’ve already discussed in a previous Forbes article, epidemiological evidence of this exists not just for SARS-CoV-2 but SARS-CoV as well, the most prominent case being an outbreak of more than 300 cases in a Hong Kong apartment complex that health officials traced back to one man’s infectious diarrhea and a defective drainage system.
More research on Covid-19 gut infection is needed to understand the full extent of its impact on the body and the pandemic at large. If we leave lesser known manifestations of this virus unaccounted for in the drugs we develop to treat it, patients will continue to slip through the cracks—just as they did in the early days of the pandemic when digestive symptoms weren’t given their due. Much as we’ve learned about SARS-CoV-2 since then, our knowledge is still nowhere near complete. The sooner we can fill these gaps in our collective understanding of the virus, the better.