In New York City Sewage, a Mysterious Coronavirus Signal
By Emily Anthes, Feb. 3, 2022, NYT

The scientists’ continuing quest to figure out where the sequences are coming from highlights both the potential of wastewater surveillance,
which can help scientists keep tabs on how the virus is evolving, and
the challenge of making sense of any anomalies pulled out of the murk.

“We really struggled trying to understand what it was that we had,”
Dr. Trujillo said.

The lineages could be coming from people whose infections have escaped detection or whose virus has not been sequenced.

But the fact that they kept turning up at the same few wastewater plants
makes this theory less likely, the researchers said, given that New Yorkers, and any variants they may be carrying, tend to move throughout the city without restriction.

Still, Dr. Dennehy speculated that the sequences could be coming from
people who are confined to long-term health care facilities in just a
few areas of the city. But he has not been able to prove it.

“We were able to pin it down to a very small area of the sewershed,”
Dr. Dennehy said. “And I emailed doctors and hospitals in those areas
and never once got a response to my emails.”

Indeed, people who have compromised immune systems may have more difficulty fighting off the virus, giving it more opportunities to mutate. Many scientists theorize that Omicron emerged from an immunocompromised patient.

Intriguingly, some of the cryptic lineages have some of the same mutations
as Omicron, or mutations in the same locations. Laboratory experiments
suggest that these lineages may also be able to evade some antibodies.

The New York City lineages might be a result of the same kind of
selective pressure to evade some of the body’s immune defenses,
the researchers theorize.

An animal origin?
---------------------
On the other hand, the lineages have been circulating for long enough
now that they should have appeared in at least one sample sequenced
from an infected person, some scientists said.

“To have something in a sewershed that you’re detecting, you need a
fair bit of it around,” said Dr. Adam Lauring, a virologist at the University of Michigan, who was not involved in the research.

Dr. Johnson, the Missouri virologist, agrees. He favors the hypothesis
that the sequences are coming from animals, perhaps a few specific
populations with limited territories. In May and June of 2021, when
the number of human Covid-19 cases in the city was low, the mysterious lineages made up a greater proportion of the viral RNA in wastewater, suggesting that they may have come from a nonhuman source.

The researchers initially considered a diverse array of potential hosts,
from squirrels to skunks. “This is a very promiscuous virus,” Dr. Johnson said. “It can infect all kinds of species.”

To narrow down the possibilities, they went back to the wastewater,
assuming that any animal that was shedding virus might be leaving its
own genetic material behind, too.

Although a vast majority of the genetic material in the water came from humans, small amounts of RNA from dogs, cats and rats were also present,
the scientists found.

Dr. Johnson has been considering rats, which roam the city by the
millions. In his lab, he created pseudoviruses — harmless, nonreplicating viruses — with the same mutations present in the cryptic sequences. The pseudoviruses were able to infect both mouse and rat cells, he found.
The original version of the virus does not appear able to infect rodents, although some other variants, like Beta, can.

“So in and of itself, that isn’t huge data, but it is at least consistent with the idea that it’s coming from rodents,” Dr. Johnson said.

Since last summer, the scientists have been working with Animal and
Plant Health Inspection Service at the U.S. Department of Agriculture
to look for signs of the virus in blood and fecal samples from local
rats. So far, they’ve come up empty.

“Maybe we’re not hitting the right animals,” Dr. Dennehy said.

Or maybe rats aren’t the source of the mystery lineages. Scientists
have repeatedly found that humans can pass the virus to animals,
especially pets, zoo animals, farmed mink and others with which they
are in frequent contact. That has raised concerns that the virus might establish itself in an animal reservoir, where it might mutate and get
passed back to humans.

But rats have not typically been high on the list of concern, and
there has not been any evidence that the virus is circulating in
wild rats. The pathway by which humans could have infected rats is
also unknown.

“Nothing makes perfect sense,” Dr. Johnson said.

But some kind of animal origin remains a possibility, scientists said.

“It’s just as plausible, if not more plausible, than a human origin,” Dr. Lauring said.

So the search continues. Dr. Johnson has developed a new technique
that can amplify only non-Omicron sequences, which should make it
easier to detect the lineages. He has also begun searching for
similar lineages in sewage samples from other states, which might
help provide further clues to their origins.

“We will know eventually,” Dr. Johnson said.

https://www.nytimes.com/2022/02/03/health/coronavirus-wastewater-new-york.html

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