The COVID death rate is a shadow of its former self, and more than two years into the pandemic, Americans seem to be breathing a sigh of relief—thanks to vaccines, their risk of death or hospitalization from the virus is greatly diminished.

But there’s more to take into account before ditching your mask, experts say—Long COVID, a new chronic condition defined by an array of symptoms that endure long after the initial COVID infection has cleared.

Long COVID may already affect between 7 and 23 million Americans who previously had the virus, or up to 7% of the U.S. population, according to the U.S. Government Accountability Office.

Different estimates of how many people are affected with Long COVID vary widely— between 10 to 80% of COVID survivors. More than half of COVID survivors report symptoms that persist after six months, Penn State College of Medicine researchers reported last year.

It’s a poorly understood condition that could disable over a billion worldwide in just a few years, says Arijit Chakravarty, a COVID researcher and CEO of Fractal Therapeutics, a drug development firm. Experts say that it’s quickly growing into a major public health concern already overwhelming primary care physicians.

“Everyone puts all the attention on death and not as much attention on morbidity and loss of quality of life,” says Dr. Panagis Galiasatos, an assistant professor at Johns Hopkins’ Division of Pulmonary & Critical Care Medicine who treats long-COVID patients. “I think we need to put more attention into not catching any kind of virus or issue.”

A difficult condition to define

So, just what is Long COVID?

Good question—researchers are still trying to figure it out. So, it depends on whom you talk to.

The World Health Organization defines Long COVID as a condition that occurs in someone who had COVID, with symptoms that cannot be explained by another diagnosis, that last for two months or more. The symptoms can persist following the initial onset, or come and go over time, the organization says, adding that a diagnosis of Long COVID usually wouldn't be made until three months after acute illness.

The Mayo Clinic defines Long COVID as a set of symptoms stemming from COVID that persist for more than four weeks after diagnosis.

In reality, Long COVID is likely an umbrella term for a combination of issues and conditions: People who have long-term COVID infections who are able to continue to spread the disease, people whose COVID after-effects clear up after a few weeks, and people with Long COVID itself, in which people aren’t infectious, but experience all kinds of symptoms for much longer.

What’s more, COVID patients whose disease was severe enough to require ICU admission may suffer post-ICU complications like muscle weakness, shortness of breath, cognitive issues, anxiety, and depression—symptoms that look a lot like Long COVID, but are not, further muddying the waters, Galiasatos says. Those issues might occur due to extended periods of immobility and ventilator use, and other traumatic medical events.

“For me, Long COVID is fatigue, chest discomfort, cognitive issues that can’t be explained by anything else,” he says.

But it can be more than that—much more, depending on the patient. Long COVID can involve a mysterious “grab bag” of symptoms that vary depending on what organ systems were affected by the virus, Galiasatos says.

“The brain controls mood, mental health, and cognition, and things like pain,” he says. “So one person, with one organ system affected can result in anxiety, depression, cognitive issues, and headaches.”

But another organ system, like the musculoskeletal system, can result in different symptoms like bone aches or burning, tightness in the chest, joint pain, and muscle spasms.

It seems like most any ailment—from ear numbness, a sensation of "brain on fire," and hallucinations—could be symptoms of Long COVID, according to a landmark July study published in British medical journal The Lancet.

The study identified more than 200 potential Long COVID symptoms in 10 organ systems, with 66 symptoms typically lasting more than seven months. Researchers surveyed nearly 4,000 sufferers with confirmed or suspected COVID from nearly 60 countries, with illness of a month or longer.

The condition also seems to be evolving as new variants evolve—at least somewhat, Galiasatos says.

“I see patients with a lot more lingering fatigue than with the Delta variants,” he says. “The prior variants seemed to cause a lot more neurological, mental health, and cognitive issues. But fatigue definitely seems to be a bigger player more recently.”

Ugly math

Vaccines are great at preventing serious illness and death, but they don’t fully prevent COVID spread, meaning even a fully vaccinated person could catch COVID and develop symptoms that linger for weeks, months, or years.

What’s more, there’s no correlation between the severity of COVID symptoms and the development of Long COVID—someone with no COVID symptoms could develop the debilitating condition, and someone with a severe case of COVID may not.

Chakravarty and his research team have developed simulations throughout the pandemic and have a record for predicting uncomfortable truths, like how rebound waves of COVID were possible even after wide distribution of the vaccine. His team’s modeling shows that those who are vaccinated but don’t take precautions against the virus can expect to get COVID once or twice a year, going forward.

Those who are fully vaccinated reduce their risk of Long COVID by about half. Assuming the entire world is vaccinated and doesn’t take precautions, and that the risk of getting Long COVID each time one gets COVID is 10%, “to be conservative,” everyone has a 5% chance of getting Long COVID each year, Chakravarty says.

Over three years, then, the chance of coming down with Long COVID is 14%. If 14% of the world’s population, nearly 8 billion, comes down with Long COVID—the math isn’t pretty, Chakravarty says.

“If the whole world was vaccinated tomorrow and we spent just three years ‘learning to live with COVID’ under the current [U.S. public health] strategy, we could have well over a billion people living with Long COVID.”

Nothing new, and everything new

A virus wreaking long-term havoc is not a new concept, according to Galiasatos.

“Post-viral consequences are not new to COVID—they’ve been well-established for many other viruses,” he says.

People who contract HPV, the human papillomavirus, are at greater risk for cancer later in life, especially cervical cancer in women. The Epstein-Barr virus, which causes mononucleosis, puts those with it at a higher risk for multiple sclerosis down the road, a recent study found. And chicken pox can cause shingles later in life, Galiasatos says.

“COVID causing a cough for six months—that’s not new to COVID. Lots of viruses can cause that,” he added.

But COVID stands out from the others given the wide array of potential long-term symptoms it can cause: “I haven’t seen another virus cause things like this,” he says.

Researchers are beginning to understand the condition better. But until they can nail the biological cause of symptoms beyond “ongoing, lingering inflammation,” treatments will be limited to management of symptoms and interventions like physical, occupational, and respiratory therapy, he says.

“We’re trying to figure out the disease more specifically,” he says. “Think of an amputation—the cure is regrowing the limb. We can’t do that, so we adapt to it as much as we can.”

Galiasatos sees many patients with symptoms so debilitating that they haven’t been able to return to work.

Among the most heartbreaking to witness: “the young patients who have cognitive impairment … struggling to find words or thoughts,” he says.

“It reminds me of patients with dementia. These are patients in their 20s and 30s who were healthy before—former CEOs and CFOs who were high-functioning who are now scared about their ability to manage their livelihoods with their impairment.”

His advice: If your aim is both to survive COVID and avoid Long COVID, “Mask and be mindful of the public settings you’re going to go in.”

“Good masks will keep you safe,” he says, referencing N95 masks.