Look up COVID-19 on any health website in the first year of the pandemic, and you’d see the same description: it’s a respiratory illness. It attacks the lungs; the main symptom was a cough; heck, you can literally see the damage it causes if you have the right equipment.
But in among all the hacking coughs and fevers, some people noticed some less lung-related symptoms. Diarrhea, for instance, or needing to throw up. And so, while much of the world concentrated on coping with what they assumed was a purely respiratory disease, a few scientists started quietly investigating how COVID interacts with the gut.
With the publication of a handful of papers over the past six months, their gamble seems to have paid off.
“We found that people who had cleared their respiratory infection – meaning they were no longer testing positive for SARS-CoV-2 in their respiratory tract – were continuing to shed SARS-CoV-2 RNA in their feces,” explained Ami Bhatt, an associate professor of medicine and genetics at Stanford University. “And those people in particular had a high incidence of GI symptoms,” she added.
Bhatt was senior researcher on one of those papers, published in the journal Med in April. But she believes the study’s findings might explain more than just the gastrointestinal symptoms of COVID-19.
“Long COVID could be the consequence of ongoing immune reaction to SARS-CoV-2,” Bhatt theorized – although it “also could be that we have people who have persistent infections that are hiding out in niches other than the respiratory tract, like the GI tract,” she said.
Long COVID – the name that’s risen for cases where symptoms from COVID linger for months or even years after the initial infection clears up – is something of a mystery. It seems to occur in somewhere between one in 10 and one in three cases, and can sometimes be completely debilitating, but what causes it, and who is most susceptible, still eludes researchers.
But Bhatt’s study is one of a growing number that suggest it may be caused, at least in part, by fragments of the original infection sticking around in the gut – COVID “ghosts,” Bhatt calls them.
“SARS-CoV-2 might be hanging out at the gut or even other tissues for a longer period of time than it sticks around in the respiratory tract, and there it can basically continue to kind of tickle our immune system and induce some of these long-term consequences,” she explained.
Bhatt’s isn’t the only research that has linked Long COVID to the gut. One early hint came in 2021, when a study published in Nature reported finding viral particles in the gastrointestinal linings of patients four months COVID-free. Another paper, not yet peer-reviewed, found COVID particles were “widely distributed” in the body tissues of recently deceased COVID patients – “even among patients who died with asymptomatic to mild COVID-19,” the paper reports, “and … virus replication is present in multiple extrapulmonary tissues early in infection. “
And more recently, appearing in the journal Gastroenterology just over two weeks after Bhatt’s paper, a team from Innsbruck, Austria, found SARS-CoV-2 RNA in the gut mucosa of irritable bowel syndrome (IBS) patients as much as seven months after the initial COVID infection was confirmed.
“Our findings indicate that viral antigens, but not infectious virions, persist in the gut mucosa long beyond mild acute COVID-19 in IBD patients,” reports the paper. “More specifically, antigen persistence occurs in 52-70 percent of patients after ~7 months in our IBD cohort … We argue that viral antigen persistence reflects incomplete clearance of SARS-CoV-2 rather than subclinical (latent or persistent) infection, as we were unable to replicate virus from biopsy-derived tissue.”
While the results are encouraging – after all, the gut is increasingly being recognized as a crucial part of the immune system – all researchers involved caution that far more study is needed before a link can be confirmed.
“Additional studies still need to be done,” Bhatt told Nature. “And they’re not easy.”