Rat droppings from New York City. Poop from a dog park in Wisconsin. Human waste from a Missouri hospital. These are some of the materials preparing us for the next chapter of the coronavirus story.
More than four years into the pandemic, the virus has loosened its grip on most people's bodies and minds. But new variants that are better able to evade our immune defenses may still emerge, potentially derailing our hard-won return to normality.
Scientists across the country are observing the first signs.
Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Institute, said the fact that most people, including scientists, are returning to pre-pandemic lifestyles is a natural sign that “we are no longer in the acute phase of the pandemic.” , I think that's probably a good thing.” Seattle Cancer Center.
“However, the virus is still evolving and is still infecting large numbers of people,” he added. “We need to keep tracking this.”
Dr. Bloom and other researchers are trying to understand how the coronavirus behaves and evolves as populations develop immunity. Other teams are investigating the body's response to infections, including a complex syndrome called long corona.
And some scientists are taking on the increasingly difficult task of estimating vaccine effectiveness in crowded breathing environments.
“This virus just becomes more intellectually interesting, at least to me,” said Sarah Corby, an evolutionary biologist at the University of Chicago.
“In some ways, SARS-CoV-2 has been a great reminder of some of the deepest questions in this field, and a reminder of how far we have to go to answer many of them. He let me.”
Mark Johnson, a virologist at the University of Missouri who has tracked repeats of the coronavirus in rodent and human stool samples, said a close analysis of new variants emerging in wastewater would be a good idea for further research. He said this could be useful in predicting which forms will surface.
“They can help inform the evolution of this virus and what happens next, and perhaps even inform how to make better vaccines,” Dr. Johnson said.
“Black Swan Event”
Evolutionary biology was once an arcane pursuit that involved hours of tedious work staring at a computer screen. The public health impact of this research has often been tenuous.
The pandemic has changed that. Vaccines can now be manufactured more easily and quickly than ever before, so “truly understanding how viruses evolve becomes increasingly practical,” Dr. Bloom said.
Many of the evolutionary biologists currently studying coronaviruses, including Dr. Bloom, were experts on influenza. Influenza evolves into new variants every two to eight years from the previous type.
Scientists expected coronaviruses to behave similarly. However, Omicron arrived with dozens of new mutations. Dr Bloom said this was a shocking “black swan phenomenon”. Then came BA.2.86, another major evolutionary leap that showed that viruses are still unpredictable.
Repetitions of a virus that multiply throughout a population have certain advantages, such as the ability to evade the immune system, or extreme infectivity. Katia Koel, an evolutionary biologist at Emory University, said that individuals “don't have that kind of evolutionary pressure.”
As a result, chronic infections (usually in immunocompromised people) give the virus a chance to experiment with new forms, allowing it to press the evolutionary equivalent of a fast-forward button. (Residual virus in the body is also thought to be involved in prolonging the novel coronavirus infection.)
Chronic coronavirus infection is rare, even among immunocompromised people. However, the Alpha variant in late 2020, the Omicron variant in late 2021, and BA.2.86, which was first detected last summer, are all now thought to have emerged from immunocompromised individuals.
Dr. Koel said some mutations that the virus acquires as it evolves may not provide any benefit or may even be a hindrance. Not all versions of the virus pose a widespread threat to people. For example, BA.2.86 ultimately did not.
But still, these genetic changes may be predictive of the future.
After BA.2.86 emerged, detailed analysis of its genome revealed one spot where the virus remained sensitive to the body's immune defenses. Dr. Johnson speculated that the virus' next move would be to acquire mutations in that very location.
“And sure enough, it's just emerging,” he said, referring to JN.1, the variant that is currently accounting for the majority of infections.
“The more we see strains like BA.2.86 that appear to be derived from chronic infections, the more there is discussion of, 'This is something we should really pay attention to,'” he added.
Dr. Johnson analyzed more than 20,000 wastewater samples from around the country and found fewer than 60 genetic sequences of the virus that likely came from immunocompromised people.
This chain of events would only occur if “super shedders” (individuals who shed large amounts of the virus in their feces) happened to live in areas where sewage monitoring was taking place. “I'm sure there are more out there,” Dr. Johnson says. “I don't know how many more there are.”
Spotty surveillance
Scientists looking for signs of new danger are constrained by limited surveillance of coronavirus variants in the United States and other countries.
Many countries, including the United States, stepped up tracing efforts at the height of the pandemic. But it has since been reduced, leaving scientists only guessing at the scale of respiratory virus infections. Wastewater and hospitalization may be clues, but neither is a sensitive measure.
“There has never been particularly systematic surveillance of respiratory pathogens in the United States, and now it is even less systematic,” Dr. Covey said. “Our understanding of the burden of these pathogens, much less their evolution, has been significantly compromised.”
Not tracking the virus closely has other consequences. The need to fight multiple respiratory viruses each year makes it extremely difficult to measure the effectiveness of vaccines.
Before COVID-19, scientists estimated the effectiveness of influenza vaccines by comparing the vaccination status of people who tested positive for the flu with those who did not.
But now, with coronavirus and RSV vaccines in the mix, the math is no longer that simple. Patients visit clinics and hospitals with similar symptoms, and each vaccine protects them to varying degrees.
“We're starting to see a much more complex prevention network,” said Emily Martin, an epidemiologist at the University of Michigan. “It does interesting things to numbers.”
Accurately estimating efficacy is critical to designing seasonal vaccines and preparing physicians and patients for the challenging respiratory season.
For example, in 2021, the University of Michigan experienced an influenza outbreak. Researchers have told other university campuses to prepare for dorm clusters and hospitals to stockpile antiviral drugs after finding this season's vaccines do not protect against this strain of the virus. I was able to warn you.
Solving the problem can itself pose complications, as different divisions of the Centers for Disease Control and Prevention work on influenza, the coronavirus, and other respiratory diseases.
“We need to solve problems across these kinds of artificial lines in different departments,” Dr. Martin said.
Immunity and prolongation of new coronavirus infection
As more and more coronavirus variants emerge, it has become clear that vaccines, while a powerful bulwark against severe illness and death, are far 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 enters the body.
“Ideally, you want to place them across mucosal sites, which means they need to be placed in the nose and lungs,” said Marion Pepper, an immunologist at the University of Washington in Seattle.
About 15 years ago, scientists discovered that most 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've been particularly focused on is trying to understand the immune response within tissues better than we had before,” Dr. Pepper said.
In a small number of people, the virus itself can also persist in different parts of the body, which could be one of the reasons for the prolonged COVID-19 infection. Vaccinations and antiviral drugs alleviate some of the symptoms, lending credence to this idea.
At Yale University, Akiko Iwasaki and colleagues are testing whether administering the antiviral drug paxlobid for 15 days can eliminate the reservoir of slowly replicating viruses in the body.
“If it's making people sick, we want to get to the root cause of it,” Dr. Iwasaki said.
She and her colleagues began studying the immune response to coronaviruses almost as soon as the virus emerged. As the pandemic progressed, the collaboration became larger and more international.
And it has become clear that the coronavirus will leave a lasting legacy of immune-related problems in many people.
Two years ago, Dr. Iwasaki proposed establishing a new center to study the myriad questions that had arisen. Infections with many other viruses, bacteria, and parasites also cause long-term complications, including autoimmunity.
Established last summer, this new virtual institute is dedicated to researching post-infectious syndromes and their prevention and treatment strategies.
Before the pandemic struck, Dr. Iwasaki was already busy researching viral infections with a large lab and multiple projects. But that doesn't compare to her own life now, she said.
“Scientists tend to be obsessed with what they're working on, but they don't have this level of urgency,” she said. “I work most of my waking hours.”