Why does Covid-19 seem to be getting milder?

XEC, the latest descendant of the omicron strain of SARS-CoV-2, arose through recombination, a process where the genetic material of two other variants recombines, creating a new strain.

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Photo: Getty Images
Disclaimer: The translations are mostly done through AI translator and might not be 100% accurate.

When virologists first took a look at XEC, the variant of Covid-19 that began to dominate in the fall of 2024, the early signs were ominous.

XEC, the latest descendant of the omicron strain of SARS-CoV-2, arose through recombination, a process where the genetic material of two other variants recombines, creating a new strain.

Studies have shown that this variant could therefore easily evade immune protection acquired from previous infections or the effects of the latest version of the Covid-19 vaccine, based on the older JN.1 and KP.2 strains.

"The spike protein (S) is quite different from previous variants, so it was easy to assume that XSEC had the potential to bypass the immunity built up by JN.1 infection," says Kei Sato, a professor of virology at the University of Tokyo, Japan, who conducted one of the first studies on XEC, published in December 2024.

In the United States (US), infectious disease experts have braced for a sharp increase in hospitalizations after the Thanksgiving holiday.

But that didn't happen.

Monitoring the risk of infection by measuring the amount of Covid-19 in wastewater samples in major cities has shown that the XEC strain definitely infects humans.

However, the number of people who actually needed hospital treatment was significantly lower than in previous winters.

According to data from the US Centers for Disease Control and Prevention (CDC), in early December 2023, the hospitalization rate was 6,1 per 100.000 people.

During the same week in December 2024, it dropped to two per 100.000 people.

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What was happening?

"Right now we're seeing a fairly small number of people who are seriously ill despite the astronomical amount of Covid in the wastewater," says Peter Chin-Hong, a professor in the Department of Health's Division of Infectious Diseases at the University of California, San Francisco.

"It just goes to show that no matter how terrifying a strain may look in the lab, the environment it lands in is much more inhospitable."

Some indicators suggest that Covid in 2025 will be a milder disease.

The once common symptoms of loss of taste and smell are becoming less common.

Although some patients are being treated in hospitals and there have been deaths, Chin-Hong says the vast majority of those infected will either have no symptoms or will have a cold so mild that some might interpret it as a seasonal allergy, such as an allergy to pollen.

Although people whose immune systems are weakened are still particularly at risk, the professor believes that the greatest risk of developing serious complications from Covid is now among those over the age of 75.

Despite this, experts advise that all at-risk groups should receive the latest Covid-19 vaccine, which can provide crucial protection against more serious illness, hospitalization and death.

While the XEC variant appears to cause milder disease, there is no guarantee that more serious variants will not emerge in the future.

This means that there is no end in sight to the threats posed by Covid-19 and that the virus should not be underestimated.

Experts expect it to continue to pose a significant and ongoing threat to public health.

The risk of developing long-term Covid has also not passed, and in some people this condition can last for years.

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At the Mount Sinai School of Medicine in New York City, associate professor of microbiology Harm van Bakel leads the Pathogen Tracking Program, which applies the latest genomics techniques to monitor bacterial, viral, and fungal infections in real time across the Mount Sinai Health System.

Van Bakel explains that the data shows that this winter the share of Covid in the total number of infections is relatively small, despite the emergence of the XEC strain.

"In the past six months, I would say it's been relatively calm," he says.

"Compared to other respiratory viruses, I would say that SARS-CoV-2, at least in people in hospitals, probably accounts for about 10 percent of all respiratory viral infections that are being recorded this season."

Even when patients are admitted to the hospital, treatment protocols have changed significantly in the last two to three years.

Chin-Hong recalls that in the past, anticoagulants or blood thinners would have been administered immediately to reduce the chances of blood clotting, but that this is no longer considered necessary.

While steroids such as dexamethasone are still used for certain severe cases, he says these are exceptions and antiviral drugs are now mostly given.

"I think omicron and its subvariants are increasingly causing milder upper respiratory cold symptoms rather than pneumonia and some of the invasive manifestations we've seen in the past like cardiovascular disease and blood clotting," Chin-Hong says.

"This means that people who are admitted to hospital tend to stay for a shorter period of time."

What is happening now

While tracking various respiratory viruses at the University of Missouri School of Medicine in the US, molecular virologist Mark Johnson is using all means to examine the amount of Covid currently circulating.

Just like Chin-Hong, he can confirm that there is a lot of it.

"We've started taking air samples in many places across the university, and it's quite rare that a sample from a student's environment doesn't have Covid," he says.

"We are still exposed all the time, but most infections are probably becoming milder."

But it wasn't easy to figure out why.

Sato explains that one of the reasons why new Covid variants often seem far scarier than they actually are is because their infectiousness is usually tested by injecting the virus into hamsters.

"But, of course, the hamsters are not vaccinated," he says.

"Hamsters are very similar to humans in 2019."

"They don't have specific immunity against SARS-CoV-2, so the situation for humans in 2025 is quite different."

Yet antibody levels, the most easily measurable type of immunity, do not appear to contribute significantly to our ability to reduce the impact of the latest strains of Covid.

Vaccination rates are declining worldwide.

According to CDC data, in the US, by the end of December last year, only 21,5 percent of adults and 10,6 percent of children had received the 2024-2025 Covid vaccine.

As Sato and his team studied the XEC variant, it appeared to easily evade neutralizing antibodies generated by infections with previous omicron subvariants.

Chin-Hong says there are two possibilities.

One is that the vast majority of people have now been vaccinated and infected so many times that their bodies have developed a powerful immune memory that recognizes what the virus now looks like, meaning new infections are quickly cleared before they can penetrate deeper into the body.

He believes that the progressively declining number of new cases of long-term Covid is another indication that this may be happening.

"Even if Covid does get in, it will now be recognized and pretty efficiently flushed out of the body," says Chin-Hong.

"In most cases, it doesn't last long enough to cause more serious illnesses or chronic problems."

"With long-term Covid, one hypothesis is that the virus triggers this unusual immune response, but if it can't survive for long, there's less risk of that happening," he says.

Another possibility is that Covid is now routinely mutating, causing it to become progressively milder until it eventually becomes similar to the common cold.

Chin-Hong says that would make sense, especially when parallels are drawn with past coronavirus outbreaks.

"People often look to examples of flu pandemics, like the 1918 Spanish flu, for clues about what might happen with Covid, but coronaviruses can be fundamentally different from influenza, so coronaviruses from the past may provide better clues for the future," says Chin-Hong.

"Overall, it seems that over time, as population immunity strengthens, the disease and long-term Covid will become less invasive, despite the virus constantly creating new variants such as XEC that look terrifying in the laboratory."

Covid could still cause more twists

So far, the Omicron strain, which emerged in November 2021 after Alpha and Delta, is the latest "supervariant" of Covid.

While dozens of subvariants have subsequently emerged over the past three years, none have indicated a radically new mutation of Covid.

However, Johnson says that if a person whose immune system is weakened now becomes infected with an older strain of Covid like the 2020 Delta, it could lead to something radically different.

He believes it could have a more drastic impact in terms of illness and hospitalizations because it would seem completely foreign to our bodies.

"They're not as widespread as they used to be, but we still occasionally discover some of these strains from the first year or two," Johnson says.

“We know that there are people who are infected with delta [the variant first detected in India in December 2020].

"If one of those older strains were to break out and start spreading more, people's immunity would be kind of confused because it would look so different from anything we've seen in the past three years."

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There is a possibility that something even stranger will happen.

Johnson says there are some early signs that Covid could become a fecal-oral virus, more similar to norovirus, cholera or hepatitis A than the common cold.

On the social network X, Johnson describes himself as a "sewage detective," and says some of the best predictions can be made by tracking Covid in sewage.

SARS-CoV-2 is known to sometimes persist in the gut for long periods of time, and Johnson and his colleagues have found a variety of people who appear to have persistent gut infections.

This was possible due to Covid viruses with unusual RNA patterns that were only observed in the sewage system and not in samples from clinical settings such as hospitals.

Each of these "mysterious genera," as they are called, is spawned anew by a certain anonymous individual.

Johnson thinks this occasionally happens because the Covid strain has acquired mutations that allow it to become a persistent gastrointestinal infection.

Because of this, he believes it's possible that SARS-CoV-2 could eventually find a way to spread via stool particles, just like other fecal-oral viruses.

"Many coronaviruses in bats spread like this," Johnson says.

"Interestingly, the evolutionary ancestors of Covid were not respiratory viruses, but enteric viruses [those that live in the intestines], which are spread by fecal-oral routes such as contaminated food, water, or contact with other people."

"So it's possible that Covid could become a fully foodborne pathogen, but it's probably not going to happen anytime soon."

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Another key question is the possible consequences of long-term gastrointestinal infection with Covid and how common it would be.

To learn more, Johnson is now trying to find people who have experienced long-term gastrointestinal problems after an acute Covid infection to conduct a trial.

Johnson believes it is particularly important for public health to try to understand some of the consequences of long-term gut infections with Covid.

He noticed that after a period of time, sometimes many years, most of the mysterious genera he repeatedly observed in wastewater eventually disappeared.

"I assume that person died, but I don't know for sure or from what," he says.

"There are many unanswered questions."

Therefore, while the vast majority of Covid infections appear to be benign, researchers like Johnson and Chin-Hong emphasize that it is still important for people to get vaccinated and for companies to continue working on developing the next generation of vaccines.

In addition to annual booster doses, Chin-Hong says the next phase in the development of Covid vaccines is nasal vaccines, which induce a mucosal immune response and can actually prevent transmission of the virus, not just serious infections and diseases.

Work is also continuing on a universal COVID vaccine that will not need to be supplemented every year.

"Ultimately, what happens next with Covid is a bit unpredictable," says Chin-Hong.

"As long as there is some risk of severe illness and hospitalization, we need better therapies and vaccines for the future, at least for some people."

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