COVID-19 long-haulers are showing early signs of neurological disorders: at least 1 in 5 still report brain fog after months

COVID recovery
A COVID-19 patient recovers at home in Brooklyn, New York on November 21, 2020.

  • Around 1 in 5 coronavirus long-haulers still felt brain fog six months after their initial infection.
  • That’s according to a new preprint analysis that collected data from nearly 19,000 patients.
  • Doctors will need to keep tracking long-haulers to know whether they have neurological disorders.
  • See more stories on Insider’s business page.

When people started reporting brain fog, dizziness, and vertigo following COVID-19 infections, doctors weren’t sure how long the issues would last. Were these symptoms the short-term byproducts of a viral illness or early signs of a neurological disorder?

Now researchers are getting closer to an answer.

A new preprint analysis, which is still awaiting peer review, found that one in five coronavirus long-haulers – people who’ve been sick with COVID-19 for roughly three weeks or more – experienced cognitive impairment at least six months after their initial infection. For many patients, this brain fog has led to memory loss or difficulty concentrating or making decisions. In some cases, patients have had to take time off work or even file for unemployment.

“Neuropsychiatric symptoms appear to be a big part of the syndromes experienced by some people surviving COVID-19,” Alasdair Rooney, a co-author of the analysis, told Insider.

Rooney’s research pooled nearly 19,000 adult patients across 51 studies, making it one of the largest examinations of neurological symptoms among long-haulers to date. The patterns were the same whether or not the participants had been hospitalized and regardless of how severe their illness was at the start.

But without knowing how long these symptoms last, doctors can’t yet classify them as neurological disorders, or even chronic illnesses. Data sets are complicated by the fact that different studies track long-haulers over varying periods of time, and from different starting points.

“Before you even get to the point of setting thresholds or a number of weeks after which you declare a chronic illness, you have to have agreements about where you’re starting measuring from,” Rooney said. “And in the studies we looked at, there isn’t any at the moment.”

Still, some evidence points to a potential link between COVID-19 and persistent neurological issues: A recent study found that 72% of coronavirus survivors who’d been diagnosed with brain disorders or damage first received those diagnoses within six months of their COVID-19 infection.

Insomnia and fatigue could be neurological issues, too

 brain scan COVID
Gabriel Cervera Rodriguez examines MRI images at the COVID-19 intensive care unit at United Memorial Medical Center in Houston, Texas on December 10, 2020.

One of the challenges in diagnosing long-term COVID-19 symptoms is that doctors are still learning the underlying mechanisms of the virus itself. For instance, researchers haven’t figured out why certain long-haulers develop fatigue, while others have chest pain or trouble breathing.

“It’s almost like for long-haulers, there’s this whole batch of symptoms and they reach their hand in and pull out a handful,” Noah Greenspan, a physical therapist who runs a pulmonary rehabilitation center in New York City, previously told Insider. “For some people, it may be the gut. Some people, it may be the autonomic nervous system. Some people, it may be the lungs.”

In addition to brain fog, 27% of coronavirus long-haulers in Rooney’s analysis reported insomnia and 24% reported fatigue. Rooney said both symptoms can be rooted in neurological issues, but that’s not the only possible cause.

“The reason we included fatigue was because we see it very commonly in the neuropsychiatric clinic,” he said. “It’s well recognized that in some people, fatigue has a physical cause and other people describe mental fatigue. And we don’t know yet which it is.”

coronavirus long hauler
Maria Romero, a coronavirus long-hauler in Stamford, Connecticut, on December 22, 2020.

Around of 19% of coronavirus patients in the analysis also reported anxiety, while 15% reported post-traumatic stress. Rooney said it’s hard to know whether these issues were direct COVID-19 symptoms, simply related to the pandemic in general, or something else. But patients should take any persistent neurological or psychiatric problems seriously, he added.

“I would always advise them, if they were concerned about it, to ask advice – in other words, err on the side of caution and not minimize it,” Rooney said.

Future studies should also consider the severity of these symptoms, he added, since brain fog may be life-altering for one person but merely inconvenient for another.

“What we need now is essentially much more research looking at these particular issues to understand: What are the limits of these symptoms?” Rooney said. “Are they functionally disabling or are they symptoms that people can live with?”

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Most coronavirus long-haulers are women. That may be because they mount a stronger immune response to the virus.

woman coronavirus
A woman wears a mask in front of a pharmacy in Oberhausen, Germany.

  • Women represent the majority of long-haulers – people with lasting COVID-19 symptoms.
  • This may be because women mount a stronger immune response to the virus than men.
  • That could lead them to develop a condition akin to an autoimmune disease.
  • Visit the Business section of Insider for more stories.

In general, men get hit harder by the coronavirus than women.

Men have almost three times the odds of requiring intensive-care treatment for COVID-19 than women, according to a December study, and 1.4 times the odds of dying from the disease.

But women may have a harder time recovering after an infection. French researchers found female long-haulers in Paris outnumber male long-haulers four to one. The findings suggest most of those long-haulers – defined as people with symptoms lasting more than eight weeks – are women around 40 years old with no preexisting medical conditions.

“If you think about who the long-haulers are, we’re talking about young women who mostly were super healthy before,” Noah Greenspan, a physical therapist who runs a pulmonary rehabilitation center in New York City, told Insider.

Greenspan created a bootcamp this summer to help long-haulers manage their symptoms. He estimates that around 85% of those who’ve signed up are women.

Greenspan also co-authored a November study that suggested women are more vulnerable to post-viral syndrome following a COVID-19 diagnosis. The study, though still awaiting peer review, compared 43 long-haulers to people who’d fully recovered from COVID-19. All but one of the long-haulers included were female, and many struggled with lingering fatigue, chest pain, fever, headaches, diarrhea, and shortness of breath.

Scientists have a working theory about this imbalance: Women seem to mount a stronger T-cell response to the virus than men, which helps their immune systems identify and destroy it. This can save their lives, but it’s a double-edged sword, since an overly robust T-cell response can lead the immune system to attack itself. In that case, the consequences of infection can lead to something akin to an autoimmune disease.

Genetic differences between men and women may play a role

Greenspan said several of his long-haul patients suffer from dysautonomia: issues related to the autonomic nervous system, such as lightheadedness, dizziness, and a rapid heartbeat.

“It’s almost like for long-haulers, there’s this whole batch of symptoms and they reach their hand in and pull out a handful,” Greenspan said. “For some people, it may be the gut. Some people, it may be the autonomic nervous system. Some people, it may be the lungs. Whatever their weak spot was, we found that COVID is very opportunistic.”

But dysautonomia is less common among male long-haul patients, he added.

“We are seeing men who seem to [recover] a little bit more quickly than women,” Greenspan said. “And I’m not sure why that is.”

coronavirus long hauler
Maria Romero, a coronavirus long-hauler, in Stamford, Connecticut, on December 22, 2020.

It’s not altogether surprising that women who get COVID-19 die at lower rates than men but struggle with more long-term symptoms. Women live longer than men on average – which might be due to biological characteristics like a stronger immune response, though the science is far from settled – but are also more likely to develop autoimmune diseases like lupus, Crohn’s, or rheumatoid arthritis.

Some researchers think the reasons for this difference are genetic: X chromosomes contain more immune-related genes than the Y chromosome. X chromosomes also hold more genes in general, creating more opportunities for mutations that could lead to an autoimmune disease. Additionally, studies have found that women have more of a gene called VGLL3 that could prompt the immune system to attack itself.

Sex hormones, too, could play a role. Estrogen helps regulate the immune response, so when estrogen levels are low, the female immune system may react too aggressively to the coronavirus. That may help explain why 77% of female long-haulers in a UK survey said their symptoms were worse prior to or during their periods, when hormone levels are at their lowest.

“We do see a lot of women during their menstrual cycles or before their menstrual cycles having certainly an increase in symptoms, but what the exact mechanism is, I don’t think we know,” Greenspan said.

Most patients with chronic fatigue syndrome are women, too

Coronavirus long-haulers often display characteristics of chronic fatigue syndrome (CFS), a disorder known clinically as myalgic encephalomyelitis. People with CFS often feel weak or foggy after too much physical activity, and the symptoms don’t improve after sleep or rest.

Like long-haulers, women with CFS roughly outnumber men four to one.

It’s possible that the coronavirus triggers CFS directly, but many researchers believe the virus causes its own, similar-looking long-term disorder. Either way, further study of CFS could yield clues about why women have a harder time recovering from the coronavirus.

chronic fatigue coronavirus
Sandra Cabreras, 57, rides an exercise bike while suffering from post-COVID fatigue.

Some research suggests that CFS is an autoimmune disease that disrupts the autonomic nervous system. When our bodies sense a threat, the system releases hormones that prepare us to either defend ourselves or run away – a “fight-or-flight” response. As a result, blood pressure rises, heart rates pick up, and breathing accelerates.

For people with CFS, even small activities like taking a walk or grabbing the mail can bring about this fight-or-flight mode.

Studies have also suggested that CFS may activate microglia – tiny cells that can trigger inflammation in the central nervous system. This could ultimately impair brain function, resulting in a lack of energy, confusion, or poor focus.

The two theories aren’t mutually exclusive: It’s possible that some people with CFS could have an autoimmune disorder, while others have a neurological one.

Long-haul cases could be similarly varied. In time, scientists may come to see long-haulers as the blanket term for a group of people with a host of different illnesses spurred by COVID-19.

Those illnesses may require distinct treatment plans. Some patients may benefit from drugs that hinder inflammation, for example, or that blunt the production of antibodies that can attack one’s own immune system. Others may require physical therapy to train their bodies not to have a fight-or-flight response to physical activity.

Greenspan said he’s studying whether a combination of treadmill exercise and oxygen therapy could help alleviate patients’ symptoms.

“There’s a whole bunch of things that, while not a cure, are certainly therapeutic for many people,” he said.

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