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As vaccines blunt the threat of severe illness and death from Covid-19, millions of people remain at risk of developing an array of less serious but potentially debilitating long-term symptoms of the disease that scientists call long Covid.

Many of the most vulnerable are among younger unvaccinated people who are unprotected against the rapidly spreading Delta variant of the coronavirus, now responsible for more than 80% of America’s growing caseload.

Long Covid—a term referring to symptoms that linger for weeks or months beyond infection—affects between 10% and 30% of people who catch the virus, including those with mild or asymptomatic infections, according to experts. In some cases, symptoms persist for more than a year.

“Even if it’s not as striking as people dying, you ignore it at your peril," said Danny Altmann, professor of immunology at Imperial College London. “In terms of healthcare burden or healthcare cost, we’re on track for this being as big a problem to us as rheumatoid arthritis, the biggest autoimmune disease in the world."

Despite a strong vaccine rollout, many Americans remain unvaccinated or only partially vaccinated. Cases are sharply rising again as states relax restrictions and the highly transmissible Delta variant spreads. That increase won’t cause as many cases of serious illness or death as in previous waves, thanks to high vaccination uptake among the oldest and most vulnerable. But it could lead to tens of thousands of new cases of long Covid, even by conservative estimates.

“Long Covid is real," said Priya Duggal, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health. “Now we have a whole group of individuals who have survived Covid who are going on into a chronic [long-term] state that will likely be with us for a really long time."

The scale of the issue has spurred governments to pour large sums into researching long Covid. The National Institutes of Health has committed $1.15 billion over four years for investigating the condition, while its U.K. counterpart has so far provided nearly £40 million, the equivalent of $54 million, to fund research projects investigating causes, diagnostic methods, and possible treatments.

Long Covid is associated with a bewildering array of possible symptoms; a recent survey of people with confirmed or suspected long Covid by researchers at University College London identified more than 200, spanning visual hallucinations, heart palpitations and memory loss.

Still, certain symptoms crop up repeatedly. The majority of people with long Covid report fatigue as the dominant symptom alongside muscle aches, difficulty sleeping and shortness of breath, according to a large study by researchers at Imperial College London. Another, smaller, cluster of patients reported predominantly respiratory symptoms, including shortness of breath and chest pain or tightness. Other studies have identified cognitive issues, or “brain fog," as another common symptom.

Although severe infection is more likely to lead to long Covid, large numbers of people who had mild cases have also suffered from persistent symptoms. The Imperial study, which surveyed a random sample of more than half a million people from across England, found that around a quarter of the 21,454 people who had suffered a mild infection reported at least one symptom lasting 12 weeks or more. Those who had suffered severe infection had even higher odds of going on to experience at least one persistent symptom, around half. The study, published on the MedRxiv preprint server, hasn’t yet been peer reviewed and so is preliminary.

Long Covid has raised alarm bells for its tendency to strike the young in a way that severe illness and death haven’t. The Imperial study found that among those aged 18 to 24, about 30% of those who had knowingly caught Covid-19 reported at least one symptom lasting 12 weeks or longer.

Harry Boby, 23 years old, is one such case. A former member of the British judo team, he worked out at the gym five times a week before coming down with a mild Covid-19 infection in September. Now, a few pull-ups can floor him for days.

“I still don’t feel myself," said Mr. Boby, adding that even mild exertion can trigger “bone-crushing fatigue." He has also suffered neurological issues ranging from memory loss to episodes of psychosis where he feels paranoid and sometimes tearful.

He has twice been signed off work on sick leave due to his symptoms, for around three months each time.

Researchers suspect that long Covid likely comprises several overlapping conditions, with different causes, and several large studies are under way to try to pin some of those down. Among the leading theories are that the virus triggers some kind of autoimmune condition, that it causes lasting physical damage to various organs, and that the virus lingers in the body long after infection.

There is no proven treatment for long Covid, although researchers in the U.K. are embarking on clinical trials to establish whether some widely available anti-inflammatory drugs such as aspirin, gout treatment colchicine and antihistamines could help. Meanwhile, hospitals are establishing dedicated clinics to help people cope with their symptoms.

“I often tell patients there’s not a magic bullet that’s going to cure them," said Louise King, a medical director at a Covid recovery clinic run by the University of North Carolina at Chapel Hill. “We just don’t know that much about it."

The UNC clinic, which started seeing patients in January, is staffed by a range of specialists including physical therapists, occupational therapists, internal medicine physicians and psychiatrists, to address the vast array of symptoms. Dr. King said that while many patients seem to slowly get better, others have been struggling with symptoms for more than a year.

“We’re seeing people out of work for months," she said. “We see people who are really stressed because even when they are working they come home and are exhausted and can’t take care of their families."

Researchers don’t yet know whether a vaccinated person who suffers a breakthrough infection has more protection against long Covid. Even so, vaccination should bring down the incidence of long Covid to the extent that it prevents infection, they say. But with more than half of Americans still not fully vaccinated—most of them in younger age groups—millions of people remain susceptible to infection, and long Covid.

It isn’t yet clear why some people experience worse symptoms than others, or why some people struggle to recover even months after their initial infection. Estimates on the proportion of people for whom long Covid is a debilitating condition vary, but it could be as high as 5%, according to Johns Hopkins’ Professor Duggal.

“It might only be a very small proportion that have that permanent damage," said Peter English, a retired consultant in communicable disease control in the U.K. “But if you’re talking about young people who can’t contribute to society by working, or require care, that can add up to be an extraordinary thing per person, quite apart from the lives it ruins."

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