“In the chaos of the first months of the coronavirus pandemic, oncologist and geneticist Ami Bhatt was intrigued by widespread reports of vomiting and diarrhoea in people infected with SARS-CoV-2,” Heidi Ledford writes over at Nature magazine. “’At that time, this was thought to be a respiratory virus,’ she says. Bhatt and her colleagues, curious about a possible link between the virus and the gastrointestinal symptoms, began to collect stool samples from people with COVID-19.Thousands of miles away from Bhatt’s laboratory at Stanford Medicine in California, gastroenterology internist Timon Adolph was puzzled by accounts of gut symptoms in infected people. Adolph and his colleagues at the Medical University of Innsbruck in Austria started to assemble specimens, too —- gastrointestinal-tissue biopsies. Two years into the pandemic, the scientists’ foresight has paid off: both teams have recently published results suggesting that pieces of SARS-CoV-2 can linger in the gut for months after an initial infection. The findings add to a growing pool of evidence supporting the hypothesis that persistent bits of virus — coronavirus ‘ghosts,’ Bhatt has called them —- could contribute to the mysterious condition called long COVID. Even so, Bhatt both urges scientists to keep an open mind and cautions that researchers have not yet nailed down a link between persistent viral fragments and long COVID. ‘Additional studies still need to be done — and they’re not easy,’ she says. Long COVID is often defined as symptoms that linger beyond 12 weeks after an acute infection. More than 200 symptoms have been associated with the disorder, which ranges in severity from mild to debilitating. Theories about its origins vary, and include harmful immune responses, tiny blood clots and lingering viral reservoirs in the body. Many researchers think that a mix of these factors contributes to the global burden of disease. An early hint that the coronavirus might persist in the body came in work published in 2021 by gastroenterologist Saurabh Mehandru at the Icahn School of Medicine at Mount Sinai in New York City and his colleagues. By then, it was clear that cells lining the gut display the protein that the virus uses to enter cells. This allows SARS-CoV-2 to infect the gut. Mehandru and his team found viral nucleic acids and proteins in gastrointestinal tissue collected from people who’d been diagnosed with COVID-19 an average of four months earlier. The researchers also studied participants’ memory B cells, which are pivotal players in the immune system. The team found that antibodies produced by these B cells were continuing to evolve, suggesting that, at six months after the initial infection, the cells were still responding to molecules made by SARS-CoV-2. Inspired by this work, Bhatt and her colleagues found that a few people continued to shed viral RNA into their stool seven months after an initial mild or moderate SARS-CoV-2 infection, well after their respiratory symptoms had ended.” Heidi Ledford, “Coronavirus ‘ghosts’ found lingering in the gut,” Nature.