Armed with emerging data drawn from over 400 infected patients in Wuhan, China, scientists on a pair of new studies suggest it may be time to rethink Covid-19 as a strictly respiratory illness.
That's because the coronavirus’ reach may extend beyond the lungs, jeopardizing the body's gastrointestinal tract, too.
According to two preliminary studies, here and here, published this month in The American Journal of Gastroenterology , diarrhea, nausea, and lack of appetite may be significant symptoms of Covid-19, even in patients who never develop respiratory symptoms or fever.
“This is, to me, becoming almost as much a GI condition as a pulmonary condition."
The studies are not peer-reviewed, and so the findings need to be validated. But they jibe with emerging case reports from other localities outside China, including the United States, the researchers say. The results suggest that clinicians may have overlooked potential coronavirus patients who presented with GI, and not respiratory, symptoms of the virus. Covid-19 may be #NotJustCough.
Brennan Spiegel, director of Cedars-Sinai Health Services Research and editor-in-chief of the The American Journal of Gastroenterology, wants to challenge how the medical and academic community has characterized Covid-19.
“This is, to me, becoming almost as much a GI condition as a pulmonary condition,” Spiegel tells Inverse. “But we're not hearing about it nearly as much because people aren't running to the hospital with watery loose stools.”
“People seek care when they can't breathe; that's an emergency. The initial wave of patients that are coming into hospitals are principally coming not because they have diarrhea, but because they have shortness of breath, cough, pneumonia.”
If the new research is replicated in larger studies, it means there may be thousands of people hit by diarrhea or vomiting who think they have an illness entirely unrelated to Covid-19. As a result, they may be unwittingly transmitting the novel coronavirus to friends, family, and strangers.
Other experts say that while the studies are interesting, it may be too soon to consider adding GI symptoms to the list of hallmark Covid-19 symptoms.
"I think it is certainly reasonable to query patients about GI symptoms, but in the absence of other symptoms, I would not recommend concluding that the individual has a high suspicion for Covid-19 infection," David Lieberman, head of Oregon Health and Science University's Gastroenterology Division, tells Inverse.
Ultimately, understanding these digestive symptoms could help clinicians diagnose Covid-19 patients better and faster than before.
The most-recent study suggesting a link analyzed GI symptoms reported by 206 people with mild cases of Covid-19. This group is representative of the estimated 75 to 80 percent of global COVID-19 cases that are considered "mild," the researchers say.
The researchers compared people with mild disease and one or more digestive symptoms (diarrhea, nausea, vomiting), with or without respiratory symptoms, to a group of people who presented with respiratory symptoms alone. The research team then tracked the course of their illness until they tested negative for Covid-19 in two separate respiratory samples. They also tested their stool.
More than half the participants reported some kind of digestive issue. Almost one in four, 24 percent, of participants presented solely with digestive symptoms. Sixty two percent of patients with a digestive symptom also had a fever. A third reported both digestive and respiratory symptoms, and 43 percent reported respiratory symptoms alone.
Among people with digestive symptoms, 67 people presented with diarrhea, of whom about one in five experienced diarrhea as their first Covid-19 symptom. The diarrhea lasted from one to 14 days, with most reporting this issue lasting for five days.
"I'm getting case reports in every day of clear-cut evidence that the virus affects the entire GI tract."
The diarrhea people are experiencing is relatively low-volume, Spiegel says.
"This isn't cholera. People are not running into the hospital dehydrated and dying, thankfully," Spiegel says. "And as a result, they're at home and are told by their doctors that they can't be tested, either because they don't meet CDC guidelines or because they don't have enough test kits."
At the same time, many doctors aren't aware that GI symptoms may be associated with Covid-19, he says.
For nearly one-third of patients, one of the major clues of Covid-19 — fever — never showed up, yet they still tested positive for the virus. Fever may not always reliably predict who has Covid-19.
The study comes hot on the heels of another pre-print study, published earlier in March in the same journal. In this study, researchers analyzed 204 people with Covid-19 in Wuhan, China.
Most presented at the hospital with fever and respiratory symptoms, but over fifty percent had at least one digestive symptom, too. Of the study participants, 78.6 percent reported a lack of appetite, and 34 percent had diarrhea.
Both studies highlight some worrying trends: People who had digestive symptoms sought medical care later and took longer to fight off the virus than those with respiratory symptoms alone.
People with digestive symptoms also waited longer for a Covid-19 diagnosis than those with respiratory symptoms alone, and were more likely to test positive for Covid-19 in their stool.
Diarrhea does not necessarily mean you have come down with Covid-19, Spiegel says. Diarrhea is extremely common, and can be sparked by stress, lactose intolerance, and irritable bowel syndrome, among other conditions.
But taken together, the research suggests clinicians should consider Covid-19 as a potential diagnosis if people experience digestive symptoms after being in contact of an infected person, or if these symptoms present with a fever.
The reason why SARS-CoV-2, the novel coronavirus that causes Covid-19, ravages the GI tract may be because it invades a type of receptor known as ACE2. These receptors are common in the lungs, but they are expressed in far greater numbers in the GI tract, Spiegel says.
The virus can replicate very efficiently in the gut, which also happens to be the largest immune organ in the body, Spiegel says. This huge viral load may then overwhelm the intestinal system, and even the liver, prompting the GI symptoms.
"I'm getting case reports in every day of clear-cut evidence that the virus affects the entire GI tract, including the colon, the small intestine, the stomach," Spiegel says.
"It seems that it can cause colitis that can cause inflammation in the colon, it can cause bleeding in the colon, and in the small bowel," he says.
In contrast, Lieberman says GI symptoms appear to be present only in a "minority of patients," although he agrees that diarrhea is the most common symptom. Liver test abnormalities have also been reported, but scientists don't know the significance of these early results yet, he says.
"The actual frequency of these issues with Covid-19 is not really known, due to lack of widespread testing for Covid-19," Lieberman says.
Basically, until more infected people are tested for GI symptoms, we won't be able to pin down exactly how prevalent GI symptoms are.
At the time of writing, the United States' Centers for Disease Control and Prevention does not include any digestive symptoms in its guidelines. The World Health Organization, by contrast, suggests "very few people" with Covid-19 will experience nausea or diarrhea.
"I can understand the reluctance to expand testing guidelines to everyone with diarrhea, because we can't keep up with even those with respiratory symptoms right now," Spiegel says.
But at some point, we have to "face the facts," he says, and recognize there is clear evidence that the GI tract is affected by Covid-19.
Public health authorities may eventually adjust their guidance to reflect the emerging data. But until then, people should take every precaution if they have new, rapid onset diarrhea or vomiting, Spiegel says.
"Be fastidious about hand cleaning, toileting, and exposing other people until it goes away," he says.
His warning fits with evidence suggesting the novel coronavirus shows up in stool samples, and that it can linger in certain environments, like bathrooms, for extended periods.
"Environmental sampling studies have repeatedly found virus in and around the toilet and bathroom," John Townes, interim head of the Oregon Health & Science University (OHSU) Infectious Diseases Division, explains. "Transmission of the virus from sources such as these may be an unappreciated mode of spread."
Ultimately, all three infectious-disease experts say hand hygiene and environmental cleaning are the key to keeping safe. Both of these strategies, in addition to social distancing and mask use when ill with respiratory symptoms, can make a very real difference.
At the same time, you can also get into some other good habits, Townes says.
"Close the toilet lid to avoid aerosols generated during flushing," he says.
And if you do start showing unexplained digestive symptoms, regardless of whether it has to do with coronavirus, it is important to stay hydrated, Lieberman says.
"Patients should be concerned and notify their health care provider if they cannot remain hydrated, or develop blood in their bowel movements," he says.
Study highlights from the pre-print study published March 31:
What is Known: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease.In this study, we sought to describe the clinical characteristics, results of stool testing for viral RNA, and outcomes of COVID-19 patients with digestive symptoms and mild disease severity.
What is New Here: We describe a unique sub-group of COVID-19 patients with low severity disease marked by presence of digestive symptoms. These patients are more likely to test positive in stool for COVID-19 RNA, to have a longer delay before viral clearance, and to experience delayed diagnosis compared to patients with respiratory symptoms but no digestive symptoms. In some cases, the digestive symptoms, particularly diarrhea, can be the initial presentation of COVID-19, and may only later or never present with respiratory symptoms or fever. These data emphasize that patients with new-onset digestive symptoms after a possible COVID-19 contact should be suspected for the illness, even in the absence of cough, shortness of breath, sore throat, or fever.