Do pockets of Covid in the gut cause long-term symptoms?

SSince the early days of the pandemic, it has been clear that some people have lost genetic material from the virus in their stool for months after catching Covid-19. The findings were initially considered a curiosity, but there is growing evidence to support the idea that persistent pockets of coronavirus – in the gut or elsewhere – could be contributing to long Covid.

Earlier this month, Professor David R Walt and his colleagues at Harvard Medical School announced that they had detected Sars-CoV-2 proteins – most often the viral spike protein – in the blood of 65% of long patients. Covid they tested, up to 12 months after their first diagnosis.

Although small and preliminary, the study provides some of the most compelling evidence yet for the idea that reservoirs of the virus could be contributing to people’s long-term poor health. “The spike protein’s half-life in the body is quite short, so its presence indicates that there must be some sort of active viral reservoir,” Walt said.

The Spike protein was not detected in the blood of Covid patients who did not have persistent symptoms.

Walt was motivated to carry out the study after previous research by his colleagues detected Covid virus genetic material (viral RNA) in stool samples from children with multisystem inflammatory syndrome (a rare but serious disease which often strikes about four weeks after catching Covid) as well as spike proteins and a leaky gut marker in their blood. Treating them with a drug that reduced intestinal permeability led to rapid clearance of the spike protein and improvement in their symptoms. Walt’s working hypothesis is that something similar can happen in people who have had Covid for a long time.

If other groups could replicate Walt’s findings, the idea that pockets of virus weren’t yet present in at least some long-time Covid patients would be “pretty much over”, Dr Amy Proal said, microbiologist at the PolyBio Research Foundation, an American non-profit organization that supports research into complex chronic inflammatory conditions: “I personally do not see a mechanism by which the spike protein could persist for long periods without the virus. [being present].”

Other groups have also found evidence that the virus continues to be present – called “viral persistence” – in patients who have recovered from Covid. In April, Ami Bhatt of Stanford University in California and colleagues reported that around 13% of individuals still excreted viral RNA in their stool four months after catching Covid, and almost 4% continued to do so at seven months. These people also often reported persistent gastrointestinal symptoms such as nausea, vomiting, and abdominal pain.

“The question is whether the continued presence of the virus in the gut or elsewhere can somehow tickle the immune system and cause lingering symptoms,” Bhatt said.

Separate research, which analyzed the gut tissues of 46 people with inflammatory bowel disease who had recovered from mild Covid, found viral RNA or protein could still be detected in 70 % of them seven months later. About two-thirds of those people reported persistent symptoms such as fatigue or memory problems – while none of those without detectable virus did.

Yet other preliminary research has recovered the virus — in some cases virus replication — from other anatomical sites, including the eyes, brain and heart, months after people were infected. .

Viral persistence is also seen in other diseases, such as Ebola, where the virus hides in “anatomical sanctuaries” such as the eyeball or testicles that are less accessible to the immune system – and which would contribute to symptoms. persistent such as joint and muscle pain, or fatigue, in many survivors.

Even so, definitive evidence that viral reservoirs contribute to long Covid is still lacking, and Bhatt would like to see more studies done before reaching that conclusion.

Some of them are already happening. For example, the US National Institutes of Health’s Recover study is looking for signs of coronavirus in stool samples and intestinal tissue from people with long-term Covid. “These types of studies will be critical to begin to untangle what the relationship between long-term viral reservoirs and long Covid might be,” Bhatt said.

If viral persistence really is causing at least a subset of symptoms in people, it could also spur investigation into antiviral drugs as a long-lasting Covid treatment. Although it may seem like a no-brainer, some virologists worry about the implications of such a decision.

“The idea of ​​giving people long-term antiviral monotherapy to try and clear the virus is quite a controversial issue because, given the degree of adaptation of the virus that we see even over short periods of time, the possibility that the virus escape is extremely high,” said Dr Deepti Gurdasani, clinical epidemiologist at Queen Mary University of London. “I think we really need to start thinking about dual or triple therapies and testing them, because we can’t really afford to create more escape mutants at this point.”

Whether it’s the scrutiny of tissue samples or the testing of antivirals, for those who have been living with Covid for a long time, some for more than two years, such studies cannot be fast enough.

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