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Our Understanding Of Long COVID's Most Dreaded Symptom Is Still Unclear

Imagine if thinking caused you physical pain.

author

Dr. Katie Spalding

Freelance Writer

clockSep 15 2022, 15:29 UTC
A purple brain with clouds on a yellow background
Fog so thick you can't see your own frontal lobe. Image: designium/Shutterstock

When COVID-19 first came onto the scene at the tail-end of 2019, the health advice was simple: it caused ten days or so of fevers, coughs, and trouble breathing, and that was about it. Since then, though, a plethora of symptoms have been added to the list, and “long COVID” – the vernacular name for a mysterious COVID-related condition that can last weeks, months, or even years after a patient has supposedly recovered from the illness – has become a way of life for millions across the world.

Unlike the acute version of COVID-19, its long-lasting cousin comes with not just physical symptoms, but some pretty extreme mental ones too. Patients can find themselves beset by things like fatigue, anxiety, depression, and memory problems, among others. 

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Perhaps worst of all is the dreaded COVID “brain fog”: a cognitive impairment that can leave people unable to read, concentrate for more than a few seconds, or even remember a conversation they’re currently having. However, despite being so serious, the medical community is still not sure what causes brain fog – or how to cure it.

Here’s what we know.

How many people get long COVID?

Depending on which study you read, long COVID can affect anywhere from five to 50 percent of people. That’s a massive margin of error, and speaks to one of the few universals of the condition: that even now, nearly three years into the COVID-19 pandemic, it still eludes definition.

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“Our understanding of why some people face ongoing symptoms after COVID is still poor,” wrote Betty Raman, Associate Professor of Cardiovascular Medicine at the University of Oxford, in an article for The Conversation.

“Much like the varying nature of long COVID symptoms, the duration and intensity of symptoms differ from person to person,” she explained. “Notably, we’ve also had difficulty pinning down the precise prevalence of long COVID (that is, what proportion of people it affects). This has been a subject of considerable debate.”

Part of this ambiguity comes down to long COVID’s seemingly endless list of symptoms – over 200, according to recent estimates. Even those which do seem to be constant are annoyingly vague. 

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A recent study published in The Lancet found core symptoms of long COVID can include chest pain, difficulties with breathing, pain when breathing, painful muscles, loss of taste or smell, tingling extremities, lump in the throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness. 

In other words, precisely the kind of things that tend to get ignored or shrugged off – even by medical professionals. To make things even more complex, that same Lancet study found that over one in twelve people who had not had COVID-19 in the previous six months also exhibited one or more of those “core” long COVID symptoms.

“Long COVID is not a new phenomenon. Various post-infection illnesses have been documented in medical literature for decades,” wrote Marie-Claire Seeley, a PhD Candidate at the University of Adelaide’s Centre for Heart Rhythm Disorders, also for The Conversation. But “lack of understanding about these syndromes is reflective of the broad stigmas attached to them,” she continued, referring to a “collective shrugging of shoulders by health authorities when it comes to providing answers for sufferers.” 

What is COVID “brain fog”?

Among all of these nebulous symptoms, one of the most distressing is also one of the least-understood: the so-called “brain fog.”

“I used to sparkle, like I could pull these things together and start to see how the universe works,” Fiona Robertson, a writer who has had brain fog for decades already, told The Atlantic. “I’ve never been able to access that sensation again, and I miss it, every day, like an ache.”

For something like one in four COVID patients, recovery from the immediate infection comes with a lingering feeling of mental sluggishness and fatigue – or being completely overwhelmed by everyday tasks. “[Brain fog] raises what are unconscious processes for healthy people to the level of conscious decision making,” Robertson explained.

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But what exactly is brain fog? Essentially, UC San Francisco neurologist Joanna Hellmuth told the Atlantic, it’s a disorder in a person’s executive function – their brain’s ability for working memory, flexible thinking, and self-control. That means that driving; running errands; even just reading texts from friends – these kinds of tasks can be transformed by brain fog into near-impossible challenges.

“There are some people who are able to carry on with their jobs and their regular lives, but they may need to take more frequent breaks between tasks,” Jacqueline Becker, a clinical neuropsychologist at Mount Sinai Hospital in New York, told the New York Times. “And then there are other people who are just completely disabled by this.”

Part of the problem with quantifying brain fog is that researchers don’t yet have the tools to deal with it. The Montreal Cognitive Assessment, which many doctors reach for as a diagnostic tool, was designed for extreme mental issues in elderly patients with dementia, for example – “[it] isn’t validated for anyone under age 55,” Hellmuth said. Even if it were, there would be clear problems with using objective criteria to measure a subjective phenomenon, she added: “a high-functioning person with a decline in their abilities who falls within the normal range is told they don’t have a problem,” she pointed out.

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Meanwhile, the specific presentation of the syndrome can make a one-time cognitive exam ill-suited for confirming brain fog. “[Patients will] do what is asked of them when you’re testing them, and your results will say they were normal,” David Putrino, who leads a long COVID rehabilitation clinic at Mount Sinai, told the Atlantic. 

“It’s only if you check in on them two days later that you’ll see you’ve wrecked them for a week.”

What causes brain fog?

Considering all this uncertainty around the condition, it’s no surprise we’re lacking hard facts on what causes it. Maybe it’s to do with massive bone marrow cells finding their way into the brain and obstructing blood flow, some studies conclude, or perhaps it’s the result of a cytokine storm. We know that COVID-19 infections can affect the amount of grey matter in the brain – but the exact mechanisms behind these syndromes are still up for debate.

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“It is well established that COVID-19 infection is associated with subsequent risks of neurological and psychiatric problems in some people including brain fog, loss of taste and smell, depression, and psychosis,” commented University of Oxford Senior Research Fellow Max Taquet. “But why this occurs remains largely unknown.”

There are theories, though – lots, actually. A study published in Nature in March 2022, which found changes in the smell and taste areas of the brain in people recovering from COVID-19, “might help explain why some people experience brain symptoms long after the acute infection,” said Taquet, although “the causes of these brain changes, whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalised patients, in children and younger adults, and in minority ethnic groups, remain to be determined.”

Other experts look for clues in long COVID-19’s similarity to other post-infection illnesses. “Such conditions bear a striking resemblance to each other,” wrote Seeley. “Two of these conditions, postural orthostatic tachycardia syndrome and myalgic encephalomyelitis or chronic fatigue syndrome, appear closely related. And their symptoms look a lot like long COVID too.”

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Under this model, she explained, the immune system goes into overdrive, inadvertently damaging the autonomic nervous system along with the SARS-CoV-2 pathogen. This sends bodily functions like the heart rate and blood pressure into dysregulation, and can provoke reactions like inflammation of the brain.

Perhaps, others suggest, brain fog is the result of a mix of things. COVID-19 has been shown to mess with the circulatory system, restricting the amount of blood that reaches the brain – not so many that neurons start dying en masse, but certainly enough that “the brain isn’t getting what it needs to fire on all cylinders,” Putrino explained

A lack of oxygen would affect energy-intensive brain processes first, he explained – processes like language and executive function – while inflammatory cells can strip neurons of their insulation, slowing down their communication and reducing the brain’s ability to learn and recall information. 

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If that’s what’s going on, brain fog would be a natural consequence – it’s the same process that causes the so-called “chemo brain” experienced by cancer patients, and is even part of the mechanism behind diseases like multiple sclerosis.

How to cope with brain fog

If you actually have COVID-19 brain fog, though, your top priority likely isn’t what caused it, but what you can do about it. Unfortunately, the answer right now seems to be “not much.”

“Some people spontaneously recover back to baseline,” Hellmuth told The Atlantic. “But two and a half years on, a lot of patients I see are no better.”

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Nevertheless, there are therapies that may help. “We try to encourage cardiovascular exercise, a good diet, sleep and social activities that are known to be beneficial for the brain,” Hellmuth told the Times – although those with long COVID must make allowances for themselves even here. Patients attempting physical or mental activity which is too strenuous – a level which will be much lower than they are used to from their pre-COVID lives – can “push themselves into a crash,” noted Robertson, who described concentration as being able to provoke “a physical reaction of exhaustion and pain, like I’ve run a marathon.”

That said, there is hope. “Contrary to popular medical opinion and widely held beliefs, effective therapies exist for underlying conditions like postural orthostatic tachycardia syndrome, which is prevalent in long COVID,” wrote Seeley. “Early intervention is key.”

The fact that brain fog is likely caused by inflammation is another cause for optimism, experts point out. Inflammation is not permanent, and therapies like antihistamines are already available to treat it. There are ongoing clinical trials testing drugs for brain fog caused by chemotherapy, and an increasing number of specialist long COVID recovery centers.

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And of course, there’s something else that might help fix Covid’s brain fog: the brain itself.

“The brain is extremely malleable,” Becker told the Times. “There is substantial evidence that the brain can recover after traumatic brain injuries and after strokes, and that gives me hope that recovery after brain fog is possible.”


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