During the turmoil of the first months of the coronavirus pandemic, oncologist and geneticist Amy Bhatt was intrigued by the widespread reports of vomiting and diarrhea in people infected with SARS-CoV-2. “At the time, it was thought it was a respiratory virus,” he says. Bhatt and his colleagues became interested in the possible link between the virus and gastrointestinal symptoms and began collecting stool samples from people with COVID-19.
Thousands of miles from Bhatt’s lab at Stanford Medical Center in California, gastroenterologist-intern Timon Adolf was shocked to learn about the intestinal symptoms of infected people. Adolf and his colleagues at the Medical University of Innsbruck in Austria also began collecting samples – a biopsy of the intestinal tissue.
Two years after the pandemic, scientists’ vision has paid off: both teams recently announced the results1,two SARS-CoV-2 particles suggest that they may remain in the gut for several months after the initial infection. Research is growing to support the hypothesis that persistent lice of the virus – the “ghosts” of the coronavirus, whom they call Bhatt – can contribute to a mysterious condition known as COVID.
However, both Bhatt urge scientists to be clear, and warn that researchers have yet to determine the link between fragments of persistent virus and long-term COVID. “Additional research still needs to be done and they are not easy,” he says.
Prolonged COVID is often defined as symptoms that last for more than 12 weeks after an acute infection. More than 200 symptoms are associated with the disorder, the severity of which varies from mild to debilitating. Theories of its origin include various and harmful immune reactions, small blood clots, and viral reservoirs in the body. Many researchers believe that a combination of these factors contributes to the global burden of the disease.
The first sign that the coronavirus could remain in the body has come into play3 Published in 2021 by Saurabh Mehandru, a gastroenterologist at Icahn Medical School in Mount Sinai, New York, and colleagues. At that time, it was clear that the cells lining the intestines represented the protein that the virus used to enter the cells. This allows SARS-CoV-2 to enter the gut.
Mehandru found viral nucleic acids and proteins in the intestinal tissue of people diagnosed with COVID-19 on average four months ago. The researchers also studied memory B cells, which are key players in the participants’ immune systems. The team found that the antibodies produced by these B cells continued to evolve, and that up to six months after the initial infection, the cells were still responding to the molecules produced by SARS-CoV-2.
Inspired by this work, Bhatt and colleagues found that several individuals continued to shed viral RNA into their feces after their respiratory symptoms had subsided seven months after a mild or moderate infection with SARS-CoV-2.1.
The virus enters the gut
Adolf said the 2021 paper inspired his team to look at biopsy samples for signs of coronavirus. They found that 32 of the 46 participants in the study showed viral molecules in their gut seven months after an acute infection with mild COVID-19. About two-thirds of those 32 people had chronic symptoms of COVID.
However, not all participants in the study were diagnosed with inflammatory bowel disease, autoimmune disease, and Adolf warns that his data do not confirm that these people have an active virus or that the viral material produces long-lasting KOVID.
At the same time, more studies have suggested the storage of viral reservoirs outside the gut. Another team examined tissue collected from autopsies of 44 people diagnosed with COVID-19 and found evidence of viral RNA in many areas, 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 reviewed.
In almost all of these individuals, COVID-19 was severely ill, but a separate study of two individuals with COVID-19 and then with prolonged COVID symptoms found viral RNA in the appendix and breast.5. Joe Yong, a pathologist at the Institute for Molecular and Cell Biology of the Agency for Science, Technology and Research in Singapore, one of the authors of the uncensored report, speculates that the virus could be infiltrated and hidden. In immune cells, called macrophages, they are found in various tissues of the body.
All of these studies support the potential for long-term viral reservoirs to contribute to long-term COVID, but researchers need to do more to provide a clear link, Mehandru said. They need to document that the coronavirus is developing in people with weakened immune systems, and they need to link such an evolution to prolonged COVID symptoms. “There’s anecdotal evidence now, but there’s a lot of unknowns,” Mehandru said
Bhatt hopes samples will be available to test the viral reservoir hypothesis. For example, the U.S. National Institutes of Health is conducting a large study called RECOVER, which aims to rule out the causes of chronic COVID and collects biopsies from the lower intestine of some participants.
But Sheng said he doesn’t have to wait for billions of dollars to get more samples: an organization of people with long-term COVID has contacted him and offered to send samples from members who have had biopsies for various reasons, such as cancer diagnosis and infection. “It’s really a coincidence, tissue can come from everywhere,” he says. “But they don’t want to wait.”