Small NIH study reveals how immune response to COVID-19 may damage brain

 A study from the National Institutes of Health describes the immune response triggered by COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurological symptoms. In a study published in Brain, researchers from the National Institute of Neurological Disorders and Stroke (NINDS) examined brain changes in nine people who died suddenly after contracting the virus.

The scientists found evidence that antibodies—proteins produced by the immune system in response to viruses and other invaders—are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. Consistent with an earlier study from the group, SARS-CoV-2 was not detected in the patients’ brains, suggesting the virus was not infecting the brain directly.    

Understanding how SARS-CoV-2 can trigger brain damage may help inform development of therapies for COVID-19 patients who have lingering neurological symptoms.   

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” said Avindra Nath, M.D., clinical director at NINDS and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

Dr. Nath and his team found that antibodies produced in response to COVID-19 may mistakenly target cells crucial to the blood-brain barrier. Tightly packed endothelial cells help form the blood-brain barrier, which keeps harmful substances from reaching the brain while allowing necessary substances to pass through. Damage to endothelial cells in blood vessels in the brain can lead to leakage of proteins from the blood. This causes bleeds and clots in some COVID-19 patients and can increase the risk of stroke.  

For the first time, researchers observed deposits of immune complexes—molecules formed when antibodies bind antigens (foreign substances)—on the surface of endothelial cells in the brains of COVID-19 patients. Such immune complexes can damage tissue by triggering inflammation.

The study builds on their previous research, which found evidence of brain damage caused by thinning and leaky blood vessels. They suspected that the damage may have been due to the body’s natural inflammatory response to the virus.

To further explore this immune response, Dr. Nath and his team examined brain tissue from a subset of patients in the previous study. The nine individuals, age 24 to 73, were chosen because they showed signs of blood vessel damage in the brain based on structural brain scans. The samples were compared to those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry, a technique that uses antibodies to identify specific marker proteins in the tissues.

As in their earlier study, researchers found signs of leaky blood vessels, based on the presence of blood proteins that normally do not cross the blood brain barrier. This suggests that the tight junctions between the endothelial cells in the blood brain barrier are damaged.

Dr. Nath and his colleagues found evidence that damage to endothelial cells was likely due to an immune response—discovering deposits of immune complexes on the surface of the cells.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together. High levels of adhesion molecules were found in endothelial cells in the samples of brain tissue.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time the tight junctions between the endothelial cells get disrupted causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”  

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, while six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. This may provide clues to the molecular basis of neurological symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, as the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the ACE2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.  

The study may also have implications for understanding and treating long-term neurological symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed Long COVID.

"It is quite possible that this same immune response persists in Long COVID patients resulting in neuronal injury,” said Dr. Nath. “There could be a small indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurological symptoms.   

 

Article:

Lee M-H, et al. Neurovascular injury with complement activation and inflammation in COVID-19. Brain. 2022.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

https://www.eurekalert.org/news-releases/957847

COVID-19 virus spike protein flexibility improved by human cell's own modifications

 When the coronavirus causing COVID-19 infects human cells, the cell’s protein-processing machinery makes modifications to the spike protein that render it more flexible and mobile, which could increase its ability to infect other cells and to evade antibodies, a new study from the University of Illinois Urbana-Champaign found.

The researchers created an atomic-level computational model of the spike protein and ran multiple simulations to examine the protein’s dynamics and how the cell’s modifications affected those dynamics. This is the first study to present such a detailed picture of the protein that plays a key role in COVID-19 infection and immunity, the researchers said.

Biochemistry professor Emad Tajkhorshid, postdoctoral researcher Karan Kapoor and graduate student Tianle Chen published their findings in the journal PNAS.

“The dynamics of a spike are very important – how much it moves and how flexible it is to search for and bind to receptors on the host cell,” said Tajkhorshid, who also is a member of the Beckman Institute for Advanced Science and Technology. “In order to have a realistic representation, you have to look at the protein at the atomic level. We hope that the results of our simulations can be used for developing new treatments. Instead of using one static structure of the protein to search for drug-binding pockets, we want to reproduce its movements and use all of the relevant shapes it adopts to provide a more complete platform for screening drug candidates instead of just one structure.”

The spike protein of SARS-CoV-2, the virus that causes COVID-19, is the protein that juts out from the surface of the virus and binds to receptors on the surface of human cells to infect them. It also is the target of antibodies in those who have been vaccinated or recovered from infection.

Many studies have looked at the spike protein and its amino acid sequence, but knowledge of its structure has largely relied on static images, Tajkhorshid said. The atomistic simulations give researchers a glimpse of dynamics that affect how the protein interacts with receptors on cells it seeks to infect and with antibodies that seek to bind to it.

They found that the protein has several “hinges” or moving parts, allowing the head of the protein to swivel on the stalk that sticks out from the virus. The researchers documented several different conformations, including active and inactive forms, and mapped how the protein shifts from one form to another. The conformations seen in their computational simulations lined up with the types and frequencies of angles observed in experimental structural studies, the researchers said, lending support to the validity of the simulations.

See a video on YouTube. 

The researchers also found that processing by the host cell changed the viral protein’s dynamics. Much research has focused on the virus’s genetic code and the mutations it has acquired as new variants emerge. However, the spike protein goes through a number of changes as it is folded and “packaged” for shipping throughout the cell. One of the most common modifications, glycosylation, is the addition of sugars called glycans at specific points. 

“Little is known about these post-translational modifications. The main role that has been noted is that glycans shield the protein from the targeting of antibodies,” Chen said. “We compared glycosylated and nonglycosylated forms of the spike protein and found significant dynamic differences between the two.”

The researchers noticed enhanced range of motion in the spike protein, making it more able to flex and interact with cell surface receptors. The glycans themselves also interacted with the cell membrane, allowing the spike protein to move and search along the membrane for the receptor.

“Glycosylations not only provide an immune shield but also mediate and enhance the mobility of the spikes, increasing the chances of the virus to successfully attach to and infect the human cells. Thus, the functions of these post-translational modifications are much wider than what was initially thought,” Kapoor said. “This understanding can now provide additional opportunities for targeting the function of this virus.”

The researchers said their findings highlight the importance of understanding not only genetic mutations in the spike protein of new virus variants, but also modifications such as glycosylation and how those modifications can add to virus infectivity and immune avoidance. They also anticipate other researchers using their models to develop new diagnostics, vaccines and antiviral drugs.

“The hope is that down the road, this new understanding of the spike protein is going to be useful for therapeutic efforts. I imagine we can target the dynamics of the spike protein with compounds that bind to the hinges and make them inflexible, and therefore in principle, make the virus less effective,” Tajkhorshid said.

The National Institutes of Health supported this work through a NIGMS grant to the NIH Resource for Macromolecular Modeling and Bioinformatics at Illinois.

Editor’s notes: To reach Emad Tajkhorshid, call (217) 244-6914; email: emad@illinois.edu.

The paper “Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors” is available online.

DOI: 10.1073/pnas.2119761119

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2119761119 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Posttranslational modifications optimize the ability of SARS-CoV-2 spike for effective interaction with host cell receptors

ARTICLE PUBLICATION DATE

23-Jun-2022

https://www.eurekalert.org/news-releases/957920

Florida 15-week abortion ban reinstated after legal appeal

 Florida’s new 15-week abortion ban was blocked and then quickly reinstated Tuesday after an appeal from the state attorney general in a lawsuit challenging the restriction.

Judge John C. Cooper issued the order temporarily halting the law after reproductive health providers argued that the state constitution guarantees the right to the procedure. The state appealed his order, automatically putting the law back into effect.

The legal back and forth came as abortion laws change at a frenzied pace across the country after the U.S. Supreme Court overturned Roe v. Wade, with several state laws and court cases shifting access to the procedure by the hour.

The Florida law prohibits abortions after 15 weeks, with exceptions if the procedure is necessary to save the pregnant woman’s life, prevent serious injury or if the fetus has a fatal abnormality. It does not allow exemptions in cases where pregnancies were caused by rape, incest or human trafficking.

Violators could face up to five years in prison. Physicians and other medical professionals could lose their licenses and face administrative fines of $10,000 for each violation.

The law was passed by the GOP-controlled legislature and signed by Republican Gov. Ron DeSantis this spring. It became effective Friday.

Data shows the majority of abortions in Florida occur before 15 weeks. A Centers for Disease Control and Prevention report said about 2% of the nearly 72,000 abortions reported in Florida in 2019 were performed after 15 weeks.

In a statement, the American Civil Liberties Union and abortion providers in the case said they would continue their suit against the law.

“The impacts of allowing this ban to remain in effect will fall hardest on people of color, those trying to make ends meet, immigrants, young people, and vulnerable populations like survivors of intimate partner violence,” the plaintiffs said. “Everyone deserves the ability to access the abortion care they need, and we’ll continue fighting for that right with every tool at our disposal.”

https://apnews.com/article/abortion-health-florida-government-and-politics-e8bdb85e6736085606ba2661c186a1d5

NC court: Restaurants can’t get insurance payouts for covid

 Over a dozen North Carolina restaurants that closed during the coronavirus pandemic when government orders restricted their services can’t be recompensed for those financial losses through their commercial insurance policies, the state Court of Appeals ruled on Tuesday.

The unanimous ruling by a three-judge panel reverses an October 2020 decision by Superior Court Judge Orlando Hudson in Durham County. He declared the language in the restaurant owners’ policies provided coverage for lost business income and extra expenses when government orders limited the access to and use of their eateries. Gov. Roy Cooper first issued a statewide order in March 2020 limiting sales to carry-out and delivery services only. Most of the restaurants that sued were located in the Triangle area.

Court of Appeals Judge Chris Dillon, writing Tuesday’s opinion, said the panel agreed with the insurers who argued the governmental restrictions didn’t result in “direct physical loss or damage to the property” that are required for payouts. Dillon cited a 1997 state court ruling, as well as recent decisions by the 4th U.S. Circuit Court of Appeals involving business interruptions caused by COVID-19 orders.

The restaurants’ “desired definition of ‘physical loss’ as a general ‘loss of use’ is not supported by our case law or the unambiguous language in the policies,” the opinion reads. Judges Toby Hampson and April Wood joined in Tuesday’s decision. Since the ruling was unanimous, the state Supreme Court wouldn’t be obligated to hear the case if the restaurant owners sought an appeal.

https://apnews.com/article/covid-health-north-carolina-state-courts-2a9c02b2b18a14d701b6ccd56f494aac

Companies could face hurdles covering abortion travel costs

 After the U.S. Supreme Court revoked the federal right to an abortion that’s been in place for half a century, companies like Amazon, Disney, Apple and JP Morgan pledged to cover travel costs for employees who live in states where the procedure is now illegal so they can terminate pregnancies.

But the companies gave scant or no details on how they will do this and it’s not clear if they will be able to — legally — while protecting employees’ privacy and keeping them safe from prosecution.

“Most employers were not prepared for Roe to be overturned, and even those that were didn’t realize the law would literally be changed the next minute,” said Brian Kropp, a vice president at the consulting firm Gartner. “They’re trying to play catch-up.”

Kropp said many companies announced plans to offer travel benefits without the infrastructure in place to make them work. Some, he added, are creating supplementary policies that employees can buy to cover abortion travel, while others are contacting insurers to see if travel can be added to their current plans. Others are trying to figure out how to offer a benefit without breaching employees’ privacy.

“Are employees going to have to tell their manager they are going to have to travel from Texas to California to have an abortion?” Kropp said.

The answer is no — but they would likely have to tell human resources or a similar department that they are pregnant and want to get an abortion, said Sharona Hoffman, a health law professor at Case Western Reserve University. The company or its health insurer would then provide money upfront or a reimbursement after the fact.

Hoffman called the travel cost pledges a “generous benefit” from companies, and said she would not be surprised “if this becomes a practice that more companies undertake — just without trumpeting it,” for fear of the backlash that can come with public statements on a divisive issue such as abortion.

“It’s not necessarily altruistic,” she said. “It also makes some sense for companies to not have a bunch of employees that are highly distressed because they have unwanted pregnancies and have to carry the child to term.”

For now, most big companies offering an abortion travel benefit will likely add it to existing health care plans, said Jonathan Zimmerman, a partner with the law firm Morgan Lewis who helps companies develop and maintain their benefits.

Big companies are generally self-insured, which means they pay for all claims and have more flexibility to decide what the plans will cover. A third party then processes the claims on their behalf.

That’s the case at outdoor clothing company Patagonia, which updated its health coverage last fall to add travel costs for employees after Texas’s law banning most abortions went into effect. Patagonia said abortion and travel costs are administered in the same manner as other medical services, ensuring confidentiality for employees.

Restaurant review company Yelp said its abortion travel benefit is also administered by its health insurance provider. Yelp has told its employees that if they do use the travel benefit, Yelp will not have access to the details of the service.

Microsoft, meanwhile, noted that it already covers abortion, as well as gender-affirming care, for its employees and has now extended the coverage to include travel expenses for “these and other lawful medical services” if they are not available in an employee’s home state.

Smaller companies may have fewer options. They typically buy health insurance for their employees from insurers that are subject to state regulations. Those companies have less flexibility to design benefits, and they may operate in states that ban abortion.

Dr. Ami Parekh, chief health officer at Included Health, which offers health care navigation services and virtual care for employers, said it is “quite a scramble” right now for large employers to navigate this fast-moving landscape.

“They’re moving as fast as they can,” Parekh said. “And I bet you they’re going to be nimble and change as needed as things come up.”

For instance, some companies are offering to pay for a partner to travel with the person getting the abortion.

With the legal landscape shifting quickly, even adding travel benefits to a current medical plan carries some risk. In May, 14 state lawmakers in Texas sent a letter to Lyft warning the company to rescind its abortion travel benefit, saying they plan to introduce legislation that would ban companies from doing business in Texas if they pay for abortions or reimburse abortion-related expenses.

That said, no such legislation has been enacted as of now in Texas or anywhere else. It is also not against the law to travel to states where abortion is legal, Hoffman noted. There are efforts afoot, however, to change that.

And while the federal Health Insurance Portability and Accountability Act, or HIPAA, protects sensitive patient information, it can be overruled in cases where a crime has been committed. That’s the case now in states where abortion has become a crime.

“It’s challenging for employers to navigate what is a rapidly evolving legal landscape,” said Sharon Masling, the head of Morgan Lewis’s reproductive rights task force. “There’s going to be a lot of litigation over the next few years.”

Beyond the legal questions, abortion travel benefits also present some thorny workplace issues, Kropp said. Employees who don’t support abortion may be angry that their company is paying for other employees’ travel, for example. Even those who do support abortion may question why the company isn’t paying them to travel for fertility treatments or transgender health care, he said.

This is why it’s likely, experts say that some companies are offering travel benefits but aren’t making public announcements about it.

“My sense is most employers are trying to very quickly figure out what’s best for their employees and dependents,” Parekh said. “And not all employers want to spend the energy to be very public about that at this moment in time.”

https://apnews.com/article/abortion-us-supreme-court-health-de9e1e2c764bf61b95aeef756a66f8a5

Many won’t rely on virtual options after COVID: AP-NORC poll

 Many Americans don’t expect to rely on the digital services that became commonplace during the pandemic after COVID-19 subsides, according to a new poll, even as many think it’s a good thing if those options remain available in the future.

Close to half or more of U.S. adults say they are not likely to attend virtual activities, receive virtual health care, have groceries delivered or use curbside pickup after the coronavirus pandemic is over, according to a poll from The Associated Press-NORC Center for Public Affairs Research. Less than 3 in 10 say they’re very likely to use any of those options at least some of the time.

Still, close to half also say it would be a good thing if virtual options for health care, for community events and for activities like fitness classes or religious services continue after the pandemic.

“Rather than this either-or, I think we’re more likely to be facing a hybrid future,” said Donna Hoffman, director of the Center for the Connected Consumer at the George Washington School of Business. “People have found convenience in some of these virtual options that just makes sense, and they don’t necessarily have anything to do with like keeping you safe or the pandemic even though they came of age during the pandemic.”

Digital daily routines became the default in 2020 as the nation reacted to the rapidly spreading virus, which prompted lockdowns, closed schools and shuttered businesses. Some substitutions, like online shopping and video conference calling, already existed. Others were reimagined or popularized during the pandemic.

Either way, Hoffman said, there was “rapid” deployment and adoption of virtual services. It was a question of “how are we going to make this work?” she said.

Cornelius Hairston said his family took precautions throughout the pandemic because his wife is a first responder in the health care field.

“We tried to stay in as much as we could and only come out for essentials,” said Hairston, 40, who recently moved to Roanoke, Virginia.

Hairston joked that his twin 4-year-old boys are “COVID babies” who didn’t even go to a grocery store for much of their young lives. The family used delivery services almost exclusively to avoid venturing out to crowded stores. But going forward, he only expects to use them “from time to time.”

For Angie Lowe, the convenience of telemedicine and time saved was reason enough to do it again even though she and her husband returned to doing things in public more than a year ago.

Lowe had her first telemedicine appointment early in the pandemic when feeling “lonely” and “stuck at home” kept her from sleeping well. She was able to talk with the doctor without having to take extra time off of work to drive to and wait in a medical center.

“It was my first telemedicine appointment, but it won’t be my last,” said Lowe, 48, of Sterling, Illinois. “If I can do it, I’m going to do it.”

For many, though, drawbacks outweigh the benefits of relying on digital services in the future. Adults age 50 or older are especially likely to say they are not planning to use the virtual options asked about on the poll going forward, even though many were introduced during the pandemic to protect the at-risk population.

Despite feeling antsy about COVID-19 and infection rates in Phoenix, Tony DiGiovane, 71, said he found curbside pickup at grocery stores and restaurants to be more hassle than they’re worth.

“By the time I picked up the stuff, I needed more stuff,” he said of his grocery orders, and “something’s always missing or wrong” on takeout orders.

Karen Stewart, 63, recognizes the benefits of video calls, but she’s also found them to be limiting. That’s the case in her job organizing after school programming for kids. She also now sees some of her doctors online, one who provides virtual care almost exclusively and another who uses virtual care in between office visits.

She likes that she doesn’t have to drive, but it means a doctor or nurse can’t take her vitals or be “hands on” in her care. It was “scary,” for example, when all of her appointments in the lead-up to a surgery were online, she said.

“When I do that they they can’t take my blood pressure, my pulse. There’s things that a doctor might pick up on that they can’t see online,” said Stewart of Perris, California.

The pandemic created an opportunity to balance in-person and virtual services to support the physical and mental health of older adults, said Alycia Bayne, a principal research scientist at NORC. That “could be particularly beneficial to older adults with different health issues, mobility limitations, people who lack transportation options, people who do not have or live near a robust social networks like family and friends to lean on,” she said.

Still, there remain limitations with technology access, broadband access and digital literacy, which Bayne said may help explain why the poll finds older adults less likely to use digital services after the pandemic.

Despite the age gap on use of services, similar percentages of adults across ages say it’s a good thing for virtual options for health care, for community events and meetings and for activities to continue after the pandemic.

“They recognize the benefits of virtual services, but they’re also ready to start getting back to their pre-pandemic routines,” she said. “The silver lining, of course, is that these services are now available.”

___

The poll of 1,001 adults was conducted May 12-16 using a sample drawn from NORC’s probability-based AmeriSpeak Panel, which is designed to be representative of the U.S. population. The margin of sampling error for all respondents is plus or minus 4 percentage points.

https://apnews.com/article/covid-technology-health-only-on-ap-fbf24abaaa800b00f1f10ae70b67af68

For COVID-19, endemic stage could be two years away

 Illnesses like the common cold and the flu have become endemic in human populations; everyone gets them every now and then, but for most people, they aren't especially harmful. COVID-19 will eventually transition to endemic status at some point—but when?

Possibly within two years, according to a new Yale study published July 5 in the journal PNAS Nexus.

To develop a better understanding of when and how COVID-19 might become endemic, Yale researchers turned to rats, which, like us, are also susceptible to coronaviruses. By collecting data on coronaviral reinfection rates among rats, they were able to model the potential trajectory of COVID-19.

There are many different types of coronaviruses, including SARS-CoV-2—the virus behind COVID-19—and several that cause the common cold. Animals like pigs and chickens live with endemic coronaviruses, too, and a key factor identified in the spread of animal and human coronaviruses alike is their tendency to evoke what's known as non-sterilizing immunity.

"It means that initially there is fairly good immunity, but relatively quickly that wanes," said Caroline Zeiss, a professor of comparative medicine at Yale School of Medicine and senior author of the study. "And so even if an animal or a person has been vaccinated or infected, they will likely become susceptible again."

Over the past two years, scientists have come to see that SARS-CoV-2 yields non-sterilizing immunity; people who have been infected or vaccinated are still at risk of reinfection. So experts expect that the virus won't go away any time soon.

To better understand what SARS-CoV-2 might do over time, scientists have used mathematical models. And given the strong similarities between animal and human coronaviruses, collecting relevant data from animals presents an opportunity to better understand SARS-CoV-2, says Zeiss.

"There are many lessons to be learned from animal coronaviruses," she said.

In this study, Zeiss and her colleagues observed how a coronavirus similar to one that causes the common cold in humans was transmitted through rat populations. The team modeled the exposure scenario to resemble human exposures in the United States, where a portion of the population is vaccinated against COVID-19 and where people continue to face natural exposure to SARS-CoV-2. They also reproduced the different types of exposure experienced by people in the U.S., with some animals exposed through close contact with an infected rat (high risk of infection) and others exposed by being placed in a cage once inhabited by an infected rat (low risk of infection).

Infected animals contracted an upper respiratory tract infection and then recovered. After three to four months, the rats were then reorganized and re-exposed to the virus. The rates of reinfection showed that natural exposure yielded a mix of immunity levels, with those exposed to more virus through close contact having stronger immunity, and those placed in a contaminated cage (and therefore exposed to lower amounts of the virus) having higher rates of reinfection.

The takeaway, Zeiss says, is that with natural infection, some individuals will develop better immunity than others. People also need vaccination, which is offered through a set dose and generates predictable immunity. But with both vaccination and natural exposure, the population accumulates broad immunity that pushes the virus toward endemic stability, the study showed.

She and her team then used this data to inform mathematical models, finding that the median time it could take for SARS-CoV-2 to become endemic in the United States is 1,437 days, or just under four years from the start of the pandemic in March 2020.

In this scenario, according to the model, 15.4% of the population would be susceptible to infection at any given time after it reaches endemic phrase.

"The virus is constantly going to be circulating," said Zeiss. So it will be important to keep more vulnerable groups in mind. "We can't assume that once we reach the endemic state that everybody is safe."

Four years is the median time predicted by the model, she said, so it could take even longer to reach the endemic stage. And this doesn't take into account mutations that could make SARS-CoV-2 more harmful.

"Coronaviruses are very unpredictable, so there could be a mutation that makes it more pathogenic," said Zeiss. "The more likely scenario, though, is that we see an increase in transmissibility and probable decrease in pathogenicity." That means the virus would be easily transmitted between people but less likely to cause severe illness, much like the common cold.

There is precedent for this trajectory. In the late 1800s, what was known as the "Russian flu" killed approximately one million people around the world. Researchers now think the virus behind that pandemic was a coronavirus that originated in cattle and eventually evolved into one of the common cold viruses still in circulation. Reduced pathogenicity associated with the transition from epidemic to endemic status has also been observed in pig coronaviruses. And almost all commercial chicken flocks across the globe are vaccinated for an endemic respiratory coronavirus that has been present since the 1930s.

Longstanding experience with coronaviral infections in other animals can help us navigate a pathway to living with SARS-CoV-2.

However, endemic stability in the United States also depends on what happens to the virus elsewhere.

"We are one global community," Zeiss said. "We don't know where else these mutations are going to arise. Until we reach endemic stability around the entire globe, we are vulnerable here to having our U.S. endemic stability disrupted by introduction of a new variant.

"But I think overall the picture's hopeful. I think we will be in endemic stability within the next year or two."

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Explore further

Common cold coronaviruses hinder antibody immune response to SARS-CoV-2 infection

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More information: Sarah Mullin et al, Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data, PNAS Nexus (2022). DOI: 10.1093/pnasnexus/pgac096

https://medicalxpress.com/news/2022-07-covid-endemic-stage-years.html