Mutations showed the virus was “running like hell.”
Tracking microbes through a foul-smelling network of sewers led virologist Marc Johnson to the source of unusual coronavirus mutants.
After months of sampling sewage, the microbiologist from the University of Missouri School of Medicine found out exactly where the mutants came from: from a regular user of the toilets at a certain Wisconsin company.
Although Johnson could not identify this individual, he was able to use genetic data to see that virus particles had been freshly made and expelled for more than a year – many times longer than a typical two-week Covid infection.
And during that time, the mutations showed the virus was “running like hell,” trying to evade the person’s immune system, Johnson said. Laboratory analysis of his sewage samples revealed the battlefield in the patient’s body where the virus was rapidly evolving to claim a stronghold.
“You can find a lot of chronic infections — people who have probably been infected for over a year — where the virus hasn’t changed at all,” he said. “And I don’t understand why it just goes crazy in some patients.”
As the scourge of Covid-19 enters its fourth year, patients like the one Johnson discovered by being traced through miles of drainpipes and drains are bringing researchers closer to answers to key questions: Where do worrying new mutants come from? And what role do they play in Long Covid, the mysterious post-infection disease that affects more than 140 million people worldwide?
Scientists are studying the possibility that some of the most contagious versions of the coronavirus — Omicron and its descendants — came from chronically infected individuals whose immune systems were weakened by illness, drugs, or both. Research published in December shows the virus can persist in the body and brain for months. That suggests it may be hiding in human cells and tissues, similar to HIV and the chickenpox virus that causes shingles.
Fascinating autopsies
Traces in the blood and stool of patients with long-lasting symptoms indicate that SARS-CoV-2 could be stored in the intestines, fat or other tissues that offer protection against the body’s immune system. Researchers from the US National Institutes of Health, who conducted painstaking autopsies on the bodies of 44 Covid victims, found viral genetic material in the bodies and brains of the patients up to 7 1/2 months after symptoms began. In one case, virus particles isolated from the brain were grown in a laboratory dish, proving that they were fully functional and capable of replication.
“The predominant damage still seems to be in the lungs,” said Daniel Chertow, who led the research in the NIH’s Emerging Pathogens Division, “but oh man, we really need to better understand what kind of damage is happening with all these others.” is done sets.”
Most of those autopsied were elderly and ill before contracting Covid, and all died before vaccines became available. And while no one was known to have had Covid for long, the findings, published in the journal Nature, still require follow-up.
“It is imperative that we try to understand in great detail what role persistence of viral RNA and other viral components might play in long-Covid,” Chertow said.
No one knows if the coronavirus or its remnants are still present in everyone who has had Covid, or if it’s just a group of patients, said Timothy Henrich, an associate professor of medicine at the University of California, San Francisco.
“We all hypothesize that it’s a driver of Long Covid, but we really haven’t shown that definitively,” Henrich said. “This is still something that needs to be done.”
Still, Chertow’s research has already inspired the experimental use of antiviral drugs like Pfizer Inc.’s Paxlovid to see if it can eradicate viral reservoirs and relieve long-term symptoms. Even a relatively small number of infected cells could trick the immune system into causing inflammation, blood clots, and other problems associated with long Covid, according to Amy Proal, co-founder of the PolyBio Research Foundation, a Boston-based nonprofit that facilitates research into chronic, infection-associated conditions .
It’s “the most logical explanation because it pretty much explains everything else,” she said.
Scan hideouts
Henrich, who has helped develop sophisticated imaging techniques capable of locating HIV in tissues, plans to use the same approach to find Covid’s hiding places. Dozens of patients will undergo a series of full-body scans looking for signals of viral protein production or persistence. These will be compared to symptoms to see how the continued presence of the coronavirus correlates to a long covid.
The group has started scanning patients to look for protective T cells that could indicate an aberrant immune response to SARS-CoV-2. They examine biopsies of the participants’ digestive tracts for traces of the virus, Henrich said.
A particular focus is on lymphoid tissues, which produce, store and transport T cells that fight infection, and antibody-producing B cells. The coronavirus could also be hiding in long-lived nerve cells and heart muscles, where it can bring on chest pain, brain fog, fatigue and other long-standing Covid symptoms, said Diane Griffin, a virologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore who has been studying for more than 50 years studying the body’s response to viral infections.
“We have pretty good information from acute RNA virus infections that RNA persists and that it has consequences,” said Griffin, who is vice president of the US National Academy of Sciences. “Basically, it’s difficult to get rid of viruses.”
Proving that prolonged viral infection causes long-term Covid will be difficult, Griffin said. Viruses in stealth mode suppress replication so as not to damage their host cells. Despite the extensive distribution of coronavirus RNA in the patients’ bodies, Chertow’s team saw little evidence of inflammation or that the immune system had attempted to destroy infected cells outside of the airways.
Viral Evolution
Interestingly, when the NIH scientists analyzed the genetic makeup of virus samples collected from six patients, they found versions in the lungs that differed from those collected in other tissues. In one patient, the viruses found in two brain regions – the thalamus and the hypothalamus – were significantly different, suggesting that certain mutations favored the pathogen’s persistence there.
“We know that these RNA viruses have the potential to evolve within a host,” Chertow said. “The more they can replicate and the longer the time they have to do so and the higher the level of replication that takes place, the more opportunity these viruses have to evolve.”
This raises an interesting possibility: as the virus evolves to inhabit different organs and tissues, the process can produce more and more infectious and immune-evasive variants. Nobody knows yet whether this is the case, but Johnson’s wastewater analysis at the University of Missouri gives the first indications.
Out of control pathogens
Since the early days of the Covid pandemic, researchers have known that Covid is capable of infecting the digestive tract, causing stomach upset and causing patients to shed traces of the virus in their faeces. Johnson routinely scans around 100 sewer networks in the Midwest for unusual SARS-CoV-2 strains, called cryptic lineages because their source is unknown.
“They’re rare, but they’re out there,” he says.
When Johnson started work in March 2021, he had no idea where the journey was going. Then, after more than a year ago, omicron drove US Covid cases to a record high, he began actively looking for strains with pronounced genetic changes.
He discovered one that came from a drain in Wisconsin that served 100,000 people. Its genetic signature was much more different than previous versions of Omicron, but it had not been reported in any patient. Importantly, its mutations appeared in newer versions of omicron. It was almost as if Johnson saw where the virus was going — evolutionarily speaking — before it arrived.
“So we started saying, let’s find out where it’s coming from,” he said.
Black Swan
For four months he and his colleagues went from one shaft to the next in an unknown metropolitan area. Then they discovered that the samples came from a building. Then one side of the building. Then half a dozen toilets, regularly used by about 30 people.
There, the investigation had come to a standstill, said Johnson. Despite this, he was able to deduce that the cryptic lineage came from an individual who was infected nearly two years ago, as it evolved from a strain last discovered in Wisconsin in April 2021.
In August, the concentration of the variant was 1.5 billion copies per liter of wastewater. For comparison, at the height of a massive Covid outbreak in a Missouri prison, a liter of sewage contained just 100 million copies of the coronavirus.
“It’s insane how much virus this person is shedding,” Johnson said.
In December, the same variant appeared in the toilet installation in Wisconsin for the 13th consecutive month.
“Whoever this person is, they still seem to be going to work every day and have been for a while,” Johnson said. “It seems they don’t know they are infected. It can’t be good for her.”
The line hasn’t appeared anywhere else, suggesting it’s not spreading, Johnson said. But there’s no question that it can grow, as evidenced by long-standing high concentrations in toilet drains.
“The question is why?” he said. “We assume something like this happened with omicron and that there was some sort of black swan event that allowed the virus to get out.”
Johnson says studying cryptic lineages challenged his thinking about the coronavirus’ ability to lodge itself in human tissues, particularly outside the respiratory system, and its potential to cause prolonged illness.
“I’m particularly open now to the idea that there are secondary infections that we just don’t know about,” he said. “And maybe that helps explain some of these very weird long Covid symptoms.”
(Except for the headline, this story was not edited by NDTV staff and was published by a syndicated feed.)
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