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Among the nearly half a billion people who have contracted COVID around the world so far, an estimated 10 to 50 percent will experience long-term symptoms. For four weeks to years after the initial diagnosis, the aftereffects of the virus may linger, affecting how patients go about their daily lives. 

Medical experts are still trying to understand why long COVID grips some patients and not others. According to a study in the journal Cell, a patient may be more prone to long-term symptoms if they experience one or more of the following biological factors: high viral load during the initial infection, a flood of autoantibodies, reactivation of the Epstein-Barr virus, and a history of Type 2 diabetes. These drivers aren’t immediately visible in patients from the outset, making it challenging to predict who eventually is at higher risk for long COVID. Some studies suggest that vaccines halve the risk of adults ending up with long COVID—but additional preliminary research suggests otherwise.

“Our knowledge of long COVID is definitely better today than it was a year ago,” says Ziyad Al-Aly, the Chief of Research and Education Service at Veterans Affairs St. Louis Health Care System. “But certainly, there’s a lot more that needs to be done, especially in the area of treatments. We don’t know what we don’t know yet.” 

In the lungs, where the virus typically takes root, SARS-Cov-2 might cause tissue damage and scarring that hinder oxygen intake. But the pathogen “can affect nearly every organ system,” Al-Aly explains. “The heart, the brain, the kidneys.” He says scientists are still puzzled by how a respiratory virus can cause so many symptoms outside the lungs, and for so long. 

An early study, posted in February without peer-review, combed through nearly 500,000 COVID patients’ health records in the UK to identify more than 115 long hauler symptoms that persisted post-infection for at least 12 weeks. While not all symptoms manifest in every patient, the current challenge is to connect the ones that do to the disease, says Al-Aly. At the initial stage of the pandemic, the suite of afflictions in long haulers was so bizarre that patients’ concerns were often dismissed by physicians or mistakenly attributed to psychological ills. 

Now, armed with more experience from tackling the fallout of the infections, medical experts have started to recognize the common ailments among long haulers and are working toward improved treatment. 

Heart and blood circulation

As a Los Angeles-based cardiologist, Alice Perlowski always took heart health very seriously. She was an endurance athlete and had several marathons under belt. But ever since she fell victim to COVID in March 2020, her blood pressure has been all over the place, she says. Her heart rate spikes when she stands abruptly—a mark of exertion for someone who used to be on her feet 12 hours plus a day at the hospital prior to the pandemic. In the first eight months after contracting COVID, she experienced chronic fatigue, which is thought to be a side effect of disrupted oxygen delivery from blood vessel damage and blood clots. 

“My job changed 180 degrees,” Perlowski says. “My entire life changed 180 degrees.” Her symptoms have improved to the point where she can now practice telemedicine from home.

Al-Aly and his team have conducted their own broad study on how COVID ravages the heart and blood vessels, but they admit that the mechanisms are still unclear. They’ve found that the virus scars and kills off heart cells, infects blood vessel linings, throws off hormonal regulation, and turns the immune system against itself. These wide-ranging reasons could partially explain why the disease devastates the body’s cardiovascular system and impairs how oxygen is distributed throughout the body for normal everyday function. 

The nervous system and brain

One of the most common symptoms of long COVID is what’s often called “brain fog”—a term Perlowski detests.  

“Brain fog sounds like you were kind of up on call all night, or with a screaming baby all night, and you are a little bit slower than normal,” she says. “But the kind of cognitive impairment that happens with this is to the point where some people have trouble reading, writing, carrying on conversations. It’s very similar to a traumatic brain injury.” 

A study published in the journal Nature in March reported that MRI brain scans on 401 COVID patients found tissue damage and the loss of gray matter. Brain atrophy was another common issue: On average, individuals showed smaller brain sizes post-infection and increased presence of cerebrospinal fluid. The patients also performed worse on basic cognitive tests compared to non-COVID sufferers. 

[Related: ‘Preliminary research’ on COVID has been surprisingly solid]

Although COVID’s myriad effects on the brain are still unclear, leading hypotheses suggest that the virus might infiltrate the cerebrum through olfactory nerves, or trigger the immune cells to attack brain cells. 

Beyond COVID’s grip on a person’s central nervous system, another insidious outcome is its impact on the autonomic nervous system. This is the network of nerves lying outside the brain that regulates various body processes running in the background of human consciousness. It governs balance and automatically adjusts heart rate and blood pressure as a person switches between different activities.  

Like Perlowski, long COVID patient Sarah (who asked PopSci not to use her real name) still finds it physically daunting to stand up from a sitting position. Walking rounds in her apartment is a momentous feat. Taking a trip to the grocery store by herself is a far-fetched dream. Even simple cognitive tasks take a chunk out of Sarah’s energy reserve, so she saves up her daily strength for communicating with her medical care team and has no room for chatting with family and friends. 

Earlier this year, she tried knitting a sock. But after three rows, “I was breathing hard and so physically exhausted, I had to nap for a couple of hours,” she writes in email. She wants the public to know “just how all-encompassing this disability is.” From landing her dream job and leading an active, full life pre-pandemic, Sarah now struggles daily to make sure she’s simply clean and fed. 

Autoimmune reactions

Before the pandemic, Sarah never experienced allergies. But in the two years since she contracted COVID, she’s developed intolerances to food and medication, random hives, and vision problems. “I feel like I’m playing a macabre game of autoimmune/inflammatory bingo, every time a new set of symptoms pops up,” she writes.

“Long COVID symptoms can really be all over the place,” says Philip A. Chan, an infectious disease physician at Brown University. “This is the category that “I would call ‘other.'” 

“My job changed 180 degrees. My entire life changed 180 degrees.”

Alice Perlowski, cardiologist

These “other” symptoms can be as far ranging as insomnia, diarrhea, hair loss, dry skin, erectile dysfunction, voice damage, and body aches. The diverse and seemingly unconnected illnesses after the initial bout of COVID defy categorization—and highlight just how extensive the virus’s reach is throughout the body.

“We’re still reminded that COVID, in general, is still a relatively new virus,” says Chan. In the first two years of the pandemic, the focus of public health policies was on containing the pandemic. Now, after Omicron’s wave crested and broke, Chan says that it’s time to shift our attention to understanding and treating long COVID in the months and years to come. 

The long hauler treatment

There are no cures for long COVID yet; current treatments only address the symptoms rather than the underlying cause. “This is one of the reasons why we should do everything we can, of course, to prevent COVID,” says Chan. “This is again another big reason why people should consider being vaccinated if they haven’t.” He adds that anyone experiencing symptoms weeks after their first COVID infection should seek help from their primary care physician as soon as possible to prevent symptoms from worsening. 

As both a physician and a long COVID patient herself, Perlowski has a front-row seat as the disease terrorizes her and her patients. “There are people who are really suffering, who have no relief and no treatment,” she says. “It’s frightening to watch.” She hopes the public is more aware of what kind of risk they’re up against, and doesn’t relax its guard, even as daily cases and death rates improve

Government agencies need to step up more too. With more states dropping their COVID restrictions, long haulers like Sarah are worried that they’ll be left to fend for themselves. She thinks getting infected with COVID again would render her not just housebound, but also bedridden. She’s worried—and angry—that she will be even more excluded from society as mask mandates are eased

Al-Aly advises those who’ve fully recovered from the virus or evaded it so far to stay cautious, and not put further strain on the country’s limited health care resources. “At the end of the day, we have to deal with facts,” he says. “We cannot just wish it away.” Because at the end of the day, the nightmare of the pandemic isn’t over for the millions of long haulers trying to survive COVID’s marks