Amid the chaos of the early months of the coronavirus pandemic, oncologist and geneticist Amy Bhatt was intrigued by widespread reports of vomiting and diarrhea in people infected with the coronavirus. “At the time, this was thought to be a respiratory virus,” she says. Bhatt and her colleagues, curious about the possible link between the virus and digestive symptoms, began collecting stool samples from people with COVID-19.
Thousands of miles away from Bhatt’s lab at Stanford Medicine in California, internist gastroenterologist Timon Adolf was baffled by accounts of infected people’s gut symptoms. Adolf and his colleagues at the Medical University of Innsbruck in Austria have begun collecting samples as well — gastrointestinal tissue biopsies.
Two years into the epidemic, the scientists’ insight has paid off: both teams have recently published the results1And the2 This suggests that pieces of SARS-CoV-2 can remain in the gut for months after initial infection. The findings add to a growing body of evidence supporting the hypothesis that persistent fragments of the virus – the “ghosts” of the coronavirus, as Bhatt called them – could contribute to the mysterious condition called COVID prolongation.
However, both Bhatt urges scientists to keep an open mind and caution that researchers have yet to prove a link between persistent viral fragments and prolonged COVID. “Additional studies are still needed – and it’s not easy,” she says.
Prolonged COVID is often defined as symptoms that persist for more than 12 weeks after an acute infection. More than 200 symptoms have been associated with this disorder, which range in severity from mild to debilitating. Theories differ about its origins, and they include harmful immune responses, micro-blood clots and viral reservoirs lingering in the body. Many researchers believe that a combination of these factors contributes to the global burden of disease.
Work started early hint that coronavirus may persist in the body3 Published in 2021 by gastroenterologist Saurabh Mehandru at Icahn School of Medicine at Mount Sinai in New York City and colleagues. By then, it was clear that the cells lining the intestine were displaying a protein that the virus uses to enter the cells. This allows SARS-CoV-2 to infect the gut.
Mihandru and his team found viral nucleic acids and proteins in digestive tissues collected from people diagnosed with COVID-19 four months ago, on average. The researchers also studied the participants’ memory B cells, which play a pivotal role in the immune system. The team found that the antibodies produced by these B cells were continuing to develop, indicating that six months after the initial infection, the cells were still responding to particles made by SARS-CoV-2.
Inspired by this work, Bhatt and colleagues found that a small number of people continued to shed viral RNA in their stool seven months after their initial mild or moderate SARS infection, after their respiratory symptoms had passed.1.
The virus is transmitted to the gut
Adolf says the 2021 paper inspired his team to look at their biopsy samples for signs of coronavirus infection. They found that 32 of the 46 study participants who had mild COVID-19 showed evidence of viral particles in their gut seven months after acute infection. About two-thirds of those 32 people had prolonged COVID symptoms.
But all of the participants in this study had inflammatory bowel disease, an autoimmune disorder, and Adolf cautions that his data do not prove that there is an active virus in these people, or that the viral substance causes COVID for a long time.
Meanwhile, more studies have suggested the presence of surviving viral reservoirs outside the gut. Another team of researchers studied tissue collected from the autopsies of 44 people diagnosed with COVID-19 and found evidence of viral RNA at several sites, including the heart, eyes and brain.4. Viral RNA and proteins were detected up to 230 days after infection. The study has not yet been peer-reviewed.
Nearly all of the people in that sample had severe COVID-19, but a separate study of two people who had mild COVID-19 followed by prolonged COVID symptoms found viral RNA in the appendix and breast.5. Pathologist Jo Young at the Institute of Molecular and Cell Biology at the Agency for Science, Technology and Research in Singapore and co-author of the report, which has not been peer-reviewed, speculates that the virus may be infiltrating and hiding. In immune cells called macrophages, which can be found in a variety of body tissues.
All of these studies support the possibility that long-term viral reservoirs may contribute to long-term COVID-19, but researchers will need to do more to definitively show the link, Mehandro says. They will need to document that coronavirus develops in people who are not immunocompromised, and they will need to correlate this development with prolonged COVID symptoms. “Currently there is anecdotal evidence, but there are a lot of unknowns,” Mehandro says.
Bhatt hopes samples will become available to test the viral reservoir hypothesis. The US National Institute of Health, for example, is running a large study called RECOVER, which aims to address the long-term causes of COVID and will collect biopsies from the lower intestines of some of the participants.
But Sheng says he doesn’t need to wait for a multibillion-dollar study to get more samples: An organization of people who have had COVID for a long time called him and offered to send samples from organs who had undergone biopsies for various reasons, such as a cancer diagnosis. after they become infected. “It’s really random, tissues can come from everywhere,” he says. “But they don’t want to wait.”