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new evidence on what causes brain fog in long covid

brain fog after a virus isn’t new, but the covid-19 pandemic has taken this post-viral symptom to an entirely new level.

brain fog and long covid: new study sheds light on treatment
researchers have found evidence of damage in the brains of patients with long covid. getty
saskia mulder, 42, says the brain fog she deals with from long covid has been “soul-destroying.”

“it’s not overtly obvious when you’re talking to me, but when i start to do things or i get tired, i’ll not be able to find words,” she told healthing . “words will come out all funny and back to front.”

mulder, a nurse and deputy ward manager in northern ireland at the start of the covid-19 pandemic, contracted the virus in march 2020. as the months progressed, so did her symptoms: chronic fatigue, severe chest pain and migraines, just to name a few. “ i now no longer recognise the … woman i was, the independence and joy from life has been stolen from me,” mulder wrote in a guest blog for tiyga health in march 2022.

before contracting covid-19 at the start of the pandemic, mulder’s work as a nurse meant she was constantly on her feet, responding to complex medical concerns as they arose and keeping track of the patients and staff on her ward. but after her illness, the trouble began.

“i ‘ve done a recent cognitive assessment test through work through occupational health, and it showed there was a deficit,” she says. “[they had me complete a maze] and i couldn’t get to the bottom. [it asked me to do] do calculations and i had to use my fingers to count …

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“i think i broke down about three times. it was actually soul-destroying.”  

the understanding that patients can experience cognitive deficits after recovering from covid-19 has slowly taken horrifying shape. a 2020 study published in the journal of psychiatric research noted slower reaction times and lower accuracy in 29 patients who had recovered from covid-19. in march 2021, an article published in the british journal of anaesthesia warned of an impending wave of “cognitive and functional decline in covid-19 survivors.”

“it’s terrifying,” says ash dobbin-mohammed, np, medical director of the rt medical post-covid clinic , a virtual clinic offering support for canadians coping with lingering effects of a covid-19 illness. “… the best analogy i can use for it is it feels as if you’re in an awake coma. you’re unable to really process your environment.”

symptoms of brain fog , which include poor concentration, feelings of confusion or “fuzzy thoughts,” trouble finding words, poor memory and mental fatigue, have been known to occur after viral illnesses before the covid-19 pandemic. however, the extent to which patients experience brain fog after covid-19 is deeply concerning, says dobbin-mohammed.

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evidence behind brain fog in long covid points to inflammation

researchers have found evidence of damage in the brains of patients with long covid, such as changes in the brain’s white matter , elevated levels of protein in the cerebrospinal fluid , and poor heart and lung function that could impact the brain.

one of the primary culprits behind brain fog is believed to be inflammation. a study published early in the pandemic noted blood markers of inflammation correlated with poor cognitive test scores. a further study from 2021 proposed the multisystem impact of inflammation on the body while fighting the virus can contribute to brain fog. (inflammation in the lungs can severely impact oxygen supply, while inflammation of the blood vessels can restrict blood flow, resulting in a one-two punch to critical organs like the brain.)

the infection and inflammation may also physically alter the connections between brain cells (neurons). research from the karolinska institute published in nature towards the end of 2022 found microglia — immune cells in the brain which defend against invading pathogens and clean up dead cells — became hyperactive in brain models infected with sars-cov-2. microglia are also thought to play a role in shaping how neurons connect with each other, trimming back weak or damaged connections. in the study, these overactive immune cells began trimming back even healthy connections between neurons (called synapses), likely contributing to the debilitating symptoms many long-covid patients experience.

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potential treatments take shape

because the onset of these symptoms came so suddenly there are few treatment options available, but specialists are beginning to see hope in treatments used for similar conditions. 

according to one small, non-blinded study published in the january 2023 edition of neuroimmunology reports , a combination of adhd and blood-pressure medication — used to treat some instances of traumatic brain injury — may help those who have experienced brain fog.

arman fesharaki-zadeh, md, behavioural neurologist and neuropsychiatrist at yale medicine, says he was struck by how similar the brain fog in patients who came to see him was to post-concussion syndrome.
“[patients with post-concussive symptoms] come into our clinics having this range of different symptoms, including difficulty with focus, difficulty with attention … they will describe going to your room not knowing why they’re there,” explains fesharaki-zadeh. “mid-task they will lose track of what they were focusing on. they tend to underperform under pressure and feel overwhelmed when there are multiple stimuli coming at them at the same time.”
fesharaki-zadeh and his team began using a similar protocol developed for patients with traumatic brain injury. the treatment includes two medications: guanfacine, an adhd medication which improves activity in the brain’s prefrontal cortex (necessary for executive functioning), and nac (n-acetylcysteine), a medication for the treatment of acetaminophen poisoning that has noted anti-oxidant and anti-inflammatory properties.

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“our work is showing that the prefrontal cortex is particularly vulnerable to inflammation, so that’s why we think that the symptoms of brain fog in particular target this part of the brain,” explains amy arnsten, professor of neuroscience and of psychology at yale university, and co-author on the paper.
eight of the twelve patients who took part in the trial reported improved working memory, concentration, and executive functioning, with some even returning to or increasing their workload after starting the medications. (two patients discontinued their involvement in the trial due to side effects, qne two more stopped for unspecified reasons.) one patient stopped the medication briefly after developing low blood pressure, but quickly reported her symptoms of brain fog had returned. she was able to adjust the medication dosage, and the brain fog again improved.
fesharaki-zadeh and arnsten are now looking to complete a larger, blinded study on the effects of these medications, and decided to publish their initial results in the meantime because of the current lack of treatment options.

the long and short road to recovery

the majority of patients who develop symptoms of long-covid after a mild infection seem to recover in under a year, according to a study in the british medical journal. however, for those experiencing the long-haul, brain fog is among the more common symptoms to persist.

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long covid is diagnosed in most nations around the world at that 12- or three-month mark,” says dobbin-mohammed. “the reason is because a lot of people around that 12 week or three-month mark tend to improve. the next point would be maybe around the six-to-eight-month mark, and then around a year.

“ … however, i find the longer that somebody has it, the slower the recovery is.”
but until widespread treatment is available, many of these patients remain unable to work. dobbin-mohammed explains this could become a slippery slope, as going for an extended period of time without using cognitive skills can, in itself, lead to cognitive decline. she encourages patients to put some focused time every day into brain training — like sudoku, crosswords or brain-game apps, while also taking adequate time to rest and heal.
into her third year of living with long-covid, mulder has searched the globe for treatment options. she first applied for diagnosis in germany and then travelled to stellenbosch, south africa, where she underwent triple anticoagulant therapy. while the treatment helped, she continues to experience fatigue and pain, and cannot return to work.

you have to go through it — all your grieving and your crying and your anger,” says mulder. “you just think this has happened and what can i do about it?

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this is part of an ongoing series. have experiences, questions, or concerns about long covid? send an email to emjones@postmedia.com
emma jones is a multimedia editor with healthing. you can reach her at emjones@postmedia.com or on instagram and twitter @jonesyjourn.
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