Rat droppings from New York City. Feces at a Wisconsin dog park. Human waste in a Missouri hospital. These are some of the materials to prepare us for the next chapter in the coronavirus saga.
More than four years into the pandemic, the virus has loosened its grip on most people’s bodies and minds. But a new variant better able to evade our immune defenses may yet emerge, undermining the hard-won return to normalcy.
Scientists across the country are watching for the first signs.
Fred Hutchinson evolutionary biologist Jesse Bloom said, “We are no longer in the severe phase of the pandemic, and I think most people, including scientists, have returned to pre-pandemic life. is understandable and probably a good thing” Seattle Cancer Center.
“That said, the virus is still evolving and still infecting large numbers of people,” he added. “We need to continue to track this.”
Dr. Bloom and other researchers are trying to understand how the coronavirus behaves and evolves as a population builds immunity. Other teams are exploring the body’s response to infection, including the complex syndrome known as long-COVID.
Some scientists have taken on the increasingly difficult task of assessing the effectiveness of vaccines in crowded respiratory environments.
“Intellectually, at least to me, this virus is only going to get more and more interesting,” said Sarah Kirby, an evolutionary biologist at the University of Chicago.
“In some ways, SARS-CoV-2 is a good reminder of some of the most profound questions in the field and how far we still have to go in answering many of them.”
Marc Johnson, a virologist at the University of Missouri who searches for iterative versions of the coronavirus in rodent and human fecal samples, said close analysis of new variants emerging in wastewater may help predict other forms that may emerge.
“They help understand the evolution of this virus and what might happen next, and may even help understand how to make a better vaccine,” Dr. Johnson said.
“Black Swan Event”
Evolutionary biology used to be an esoteric study that required hours of staring at a computer screen. The impact of this work on public health is often minimal.
The pandemic changed that. Dr Bloom said vaccines could now be made more easily and faster than before, so “really understanding how viruses evolve has more and more practical uses”.
Many evolutionary biologists now studying coronaviruses, including Dr. Bloom, are experts on influenza, which evolves into a new variant every two to eight years starting from its most immediate predecessor.
Scientists expect coronaviruses to behave similarly. But Omicron introduced dozens of new mutations — a shocking “black swan event,” Dr. Bloom said. Then came BA.2.86, another giant leap in evolution that showed the virus was still unpredictable.
Iterations of a virus that thrive in a human population have some kind of advantage—perhaps being able to evade the immune system, or being extremely contagious. “There’s no such evolutionary pressure” on individuals, says Katia Koelle, an evolutionary biologist at Emory University.
As a result, chronic infection (often in immunocompromised people) provides the virus with an opportunity to try new forms, pushing the fast-forward button on its evolution. (viral persist in Also considered in vivo play a role During the long COVID pandemic. )
chronic infection with coronavirus is Rare, even in immunocompromised people people. But the Alpha variant in late 2020, the Omicron variant in late 2021, and BA.2.86 – first detected last summer – are now thought to come from immunocompromised people.
Some mutations acquired as the virus evolves may not be of any benefit at all and may even hinder it, Dr. Kohler said. Not all versions of the virus pose a widespread threat to humans—BA.2.86, for example, ultimately posed no threat.
But these genetic changes could be a harbinger of the future.
After BA.2.86 emerged, careful analysis of its genome revealed a point at which the virus remains sensitive to the body’s immune defenses. Dr. Johnson speculates that the virus’s next move will be to mutate at that location.
“Sure enough, it showed up,” he said. See JN.1this variant now accounts for the vast majority of infections.
“The more we see lineages like BA.2.86 that appear to come from chronic infections, the more we have the argument that, like, hey, this is really something we should be concerned about,” he added.
Dr. Johnson analyzed more than 20,000 wastewater samples from across the country and found fewer than 60 viral genetic sequences that may have come from immunocompromised people.
Such sequences would only emerge if “superspreaders”—individuals who spread large amounts of the virus in their feces—happened to live in areas with wastewater surveillance. “I’m sure there are more,” Dr. Johnson said. “I just don’t know how many more there are.”
Monitoring is unstable
Scientists looking for signs of new dangers are hampered by limited surveillance of coronavirus variants in the United States and elsewhere.
Many countries, including the United States, stepped up tracing efforts at the height of the epidemic. But they were later cut back, leaving scientists guessing about the scale of respiratory viral infections. Wastewater and hospitalizations can provide clues, but are not sensitive indicators.
“We have never had particularly systematic surveillance for respiratory pathogens in the United States, but now it is even less systematic,” Dr. Bryant said. “Our understanding of the burden of these pathogens, let alone their evolution, has been really compromised.”
Not tracking viruses closely has another consequence: With multiple respiratory viruses to fight each year, measuring the effectiveness of vaccines is now extremely challenging.
Before the COVID-19 pandemic, scientists assessed the effectiveness of the flu vaccine by comparing the vaccination status of people who tested positive for the flu and those who did not.
But now, with the advent of COVID-19 and respiratory syncytial virus vaccines, the calculation is no longer simple. Patients are showing up in clinics and hospitals with similar symptoms, which each vaccine prevents to varying degrees.
“The prevention network that’s happening is getting more complex,” said Emily Martin, an epidemiologist at the University of Michigan. “It has an interesting impact on the numbers.”
Accurate estimates of effectiveness are critical to designing vaccines for each season and preparing doctors and patients for difficult respiratory seasons.
For example, in 2021, there was an influenza outbreak at the University of Michigan. When researchers found that season’s vaccines did not protect against this strain of the virus, they were able to warn other college campuses to prepare for gatherings in dormitories and warn hospitals to stockpile antiviral drugs.
Addressing the issue could present complications of its own, as different parts of the Centers for Disease Control and Prevention work on influenza, coronavirus and other respiratory illnesses.
“This requires solving problems across artificial boundaries across sectors,” Dr. Martin said.
Immunity and long-term COVID-19
As coronavirus variants emerge, it’s become clear that while vaccines offer a powerful bulwark against severe illness and death, they are much less effective at stopping the spread of the virus.
For a vaccine to prevent infection, it must induce antibodies not only in the blood but also at the site where the virus invades the body.
“Ideally, you want them to go through mucosal sites — so, in your nose, in your lungs,” said Marion Pepper, an immunologist at the University of Washington in Seattle.
About 15 years ago, scientists discovered that much of the body’s defenses come not only from the cells and organs of the immune system but also from these other tissues.
“One of the things we’re really focused on is trying to understand immune responses in tissues better than we’ve ever done before,” Dr. Pepper said.
In a small number of people, the virus itself may also persist in various parts of the body and may be a contributor to long-term COVID-19 infection.vaccination and antiviral drugs Alleviating some of the symptoms makes the idea more believable.
At Yale University, Akiko Iwasaki and her colleagues are testing whether a 15-day course of the antiviral drug Paxlovid can eliminate reservoirs of the slowly replicating virus in the body.
“If this is what’s causing people to get sick, we want to be able to find the underlying cause,” Dr. Iwasaki said.
She and her colleagues began studying the immune response to the coronavirus almost as soon as the virus emerged. As the epidemic develops, the scale of cooperation continues to expand and become more international.
It’s clear that the coronavirus has left a lasting legacy of immune-related problems in many people.
Two years ago, Dr. Iwasaki proposed establishing a new center to study the myriad problems that had arisen. Infections with many other viruses, bacteria, and parasites can also cause long-term complications, including autoimmunity.
The new virtual institute, launched last summer, is dedicated to studying post-infectious syndromes and strategies to prevent and treat them.
Before the pandemic, Dr. Iwasaki was already busy studying viral infections in a large lab and on multiple projects. But she said it was incomparable to her current life.
“Scientists tend to be obsessed with what they’re studying, but not with such urgency,” she said. “I was working almost every waking hour.”
