Rat droppings from New York. Poop from Wisconsin dog parks. Human waste from a Missouri hospital. These are just a few of the materials that prepare us for the next chapter of the coronavirus saga.
More than 4 years into the pandemic, the virus has loosened its grip on most individuals’s bodies and minds. However, a brand new variant may yet emerge that is best in a position to evade our immune defenses, derailing the hard-fought return to normality.
Scientists across the country are waiting for the first signs.
“We’re not in the acute phase of the pandemic anymore, and I think it’s understandable and probably good” that almost all people, including scientists, have returned to pre-pandemic life, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Center in Seattle.
“That said, the virus is still evolving and continues to infect large numbers of people,” he added. “We need to keep track of this.”
Dr. Bloom and other researchers try to know how the coronavirus behaves and evolves as populations construct immunity. Other teams are studying the body’s response to infection, including a fancy syndrome called long Covid.
Some scientists have taken on an increasingly difficult task: estimating vaccine effectiveness in crowded respiratory environments.
“Intellectually, this virus, at least to me, is becoming more and more interesting,” said Sarah Cobey, an evolutionary biologist at the University of Chicago.
“In some ways, SARS-CoV-2 has been a fantastic reminder of some of the deepest questions in this field, and how far we have to go to answer many of them.”
Careful evaluation of recent variants emerging in wastewater may also help predict what additional forms may emerge, said Marc Johnson, a virologist at the University of Missouri who has searched for iterations of the virus in stool samples from rodents and humans.
“They help inform the evolution of this virus and what is likely to happen next, and maybe they can even inform how to create a better vaccine,” Dr. Johnson said.
“Black Swan Event”
Evolutionary biology was once an esoteric pursuit that involved boring hours watching a pc screen. The public health implications of the work were often questionable.
The pandemic modified that. Vaccines can now be produced more easily and far faster than before, so “a true understanding of how viruses evolve is of increasing practical utility,” Dr. Bloom said.
Many of the evolutionary biologists who currently study the coronavirus, including Dr. Bloom, were experts in influenza, which evolves from its immediate predecessor right into a latest variant every two to eight years.
Scientists expected the coronavirus to behave similarly. But Omicron arrived with dozens of recent mutations – a shocking “black swan event,” Dr. Bloom said. Then got here BA.2.86, one other huge leap in evolution, signaling that the virus remained unpredictable.
Iterations of the virus that evolve throughout the population have some advantage – perhaps the ability to evade the immune system or be uniquely contagious. In a person, “there is no such evolutionary pressure,” said Katia Koelle, an evolutionary biologist at Emory University.
As a result, chronic infection – often in immunocompromised people – gives the virus the opportunity to experiment with latest formats, allowing it to hit the evolutionary equivalent of the fast-forward button. (Viral durability in the body play a task in long Covid.)
Chronic infections with coronavirus rare, even in immunocompromised people People. However, the Alpha variant in late 2020, the Omicron variant in late 2021 and the BA.2.86 variant, first detected last summer, are all now believed to have originated in immunocompromised people.
Some mutations acquired during the evolution of the virus may provide no profit or may even hinder it, says Dr. Koelle. Not all versions of the virus pose a widespread threat to the population – BA.2.86, for instance, ultimately didn’t.
Nevertheless, these genetic changes could also be an indication of the future.
After the BA.2.86 virus emerged, careful evaluation of its genome revealed one place where the virus remained vulnerable to the body’s defenses. Dr. Johnson guessed that the virus’s next move can be to mutate at this point.
“And sure enough, he just showed up,” he said, referring to JN.1that’s, the variant that currently causes the overwhelming majority of infections.
“The more we see these genetic lineages like BA.2.86 that appear to come from chronic infections, the more we have an argument like, ‘Hey, this is really something we should pay attention to,'” he added.
Analyzing greater than 20,000 sewage samples from across the country, Dr. Johnson discovered fewer than 60 genetic sequences of the virus that likely got here from immunocompromised people.
Such sequences only appear when a “super shedder” – someone who sheds huge amounts of the virus of their stools – lives in a wastewater surveillance area. “I’m sure there are many more,” Dr. Johnson said. “I just don’t know how much longer.”
Irregular supervision
Scientists searching for signs of a renewed threat are hampered by limited surveillance of coronavirus variants in the United States and other countries.
Many countries, including the United States, stepped up monitoring efforts at the height of the pandemic. However, they’ve since been restricted, leaving scientists to guess the scale of respiratory viral infections. Sewage and hospitalizations can provide clues, but neither is a sensitive measure.
“We have never had particularly systematic surveillance of respiratory pathogens in the United States, but it is even less systematic now,” Dr. Cobey said. “Our understanding of the burden of these pathogens, much less their evolution, has been truly compromised.”
The lack of accurate virus tracking has one other consequence: With so many respiratory viruses to fight every year, it’s currently extremely difficult to evaluate the effectiveness of vaccines.
Before Covid, scientists assessed the effectiveness of the flu vaccine by comparing the vaccination status of people that tested positive for flu with those that didn’t.
But now that we’re dealing with vaccines against Covid and respiratory syncytial virus, the math is not any longer easy. Patients with similar symptoms come to clinics and hospitals, and every vaccine prevents these symptoms to various degrees.
“It becomes a much more complex web of prevention,” said Emily Martin, an epidemiologist at the University of Michigan. “It does funny things to numbers.”
Accurately estimating effectiveness can be crucial in designing a vaccine for every season and preparing doctors and patients for a difficult respiratory season.
For example, in 2021, there was a flu epidemic at the University of Michigan. When scientists discovered that the seasonal vaccine didn’t protect against this strain, they were in a position to warn other college campuses to arrange to prepare clusters of their dorms and hospitals to top off on antiviral drugs.
Solving the problem itself could pose complications as different departments inside the Centers for Disease Control and Prevention deal with flu, Covid and other respiratory diseases.
“It requires solving problems across these kinds of artificial lines of different departments,” Dr. Martin said.
Immunity and long Covid
As more variants of the virus emerged, it became clear that while vaccines provided powerful protection against serious illness and death, they were much less effective at stopping the spread of the virus.
For a vaccine to forestall infections, it must induce antibodies not only in the blood but in places where the virus attacks the body.
“Ideally they would be on the mucous membranes, i.e. in the nose and lungs,” said Marion Pepper, an immunologist at the University of Washington in Seattle.
Scientists discovered about 15 years ago that a big a part of the body’s defense mechanisms come not only from the cells and organs of the immune system, but additionally from other tissues.
“One of the things we’ve really focused on is understanding immune responses in tissues better than before,” Dr. Pepper said.
In a small group of individuals, the virus itself can even persist in several parts of the body and will be certainly one of the causes of long-term Covid illness. Vaccinations i antiviral drugs alleviate some symptoms, which makes this thesis more credible.
At Yale University, Akiko Iwasaki and her colleagues are testing whether a 15-day course of the antiviral drug Paxlovid can eliminate the slowly replicating reservoir of the virus in the body.
“We hope to get to the root cause, if that’s what’s causing disease in people,” Dr. Iwasaki said.
She and her colleagues began studying immune responses to the coronavirus almost immediately after it appeared. As the pandemic progressed, cooperation became broader and more international.
It has change into clear that for many individuals, the coronavirus is leaving a long-lasting legacy of immune system problems.
Two years ago, Dr. Iwasaki proposed the creation of a brand new center where the myriad emerging questions might be explored. Infections with many other viruses, bacteria and parasites also cause long-term complications, including autoimmune diseases.
The latest virtual institute, launched last summer, studies post-infectious syndromes and techniques to forestall and treat them.
Before the pandemic, Dr. Iwasaki was already busy studying viral infections in a big laboratory and on multiple projects. But it couldn’t be in comparison with her life now, she said.
“Scientists tend to obsess about things they are working on that are not that urgent,” she said. “I pretty much work at all hours of the day.”
