Although the majority of individuals recover from COVID-19 without residual symptoms, some, even those who had a mild case, continue to have symptoms for weeks, and even months, following the initial infection. This situation is being referred to as post-COVID syndrome, long COVID, or “long-hauler” syndrome.

The long-term effects are due in part to the damage the virus can cause to the lungs, heart, and brain. While these effects are more likely to affect older individuals and/or those with underlying chronic health conditions, younger individuals can also suffer from long-term effects.

Symptoms can include:1

  1. Fatigue
  2. Shortness of breath
  3. Cough
  4. Joint and muscle pain
  5. Chest pain
  6. Loss of taste and smell
  7. Headaches
  8. Fast or pounding heart rate
  9. Sleep problems
  10. Rashes
  11. Hair loss
  12. Anxiety/depression
  13. Poor memory/brain fog

Physical effects can include:1

  1. Heart damage from small blockages in the capillaries
  2. Blood clots in legs, liver, kidneys
  3. Lung damage to the alveoli (tiny air sacs)
  4. Leaky blood vessels
  5. Brain and nerve damage due to capillary blockage

This latter phenomenon that affects the brain, and which causes the now familiar term – “post-COVID brain fog” – is the focus of this blog.

Post-COVID brain fog – what is it?

The term brain fog isn’t new. There are numerous causes of brain fog and potential solutions for brain fog that we have written about previously at Take 5 magazine. In fact, before post-COVID brain fog, there was “pandemic brain fog,” which refers to the condition associated with the pandemic in general – caused by social isolation, stress, lack of sleep, etc. Often the underlying causes of brain fog are vague or unknown.

COVID-19, however, has emerged as a very specific cause of brain fog. During the acute phase of COVID, some individuals experience delirium and an altered state of awareness. This occurs most often in patients, particularly elderly ones, who have a severe case. However, some individuals – young or old – continue to have lingering post-infection symptoms – ongoing cognitive sluggishness – often described as “brain fog” and clinically referred to as dysexecutive syndrome. This circumstance can occur, even in cases where the original infection was mild.

Individuals who experience it describe an inability to think clearly, poor memory, grasping for words, or difficulty completing simple tasks. Some report feeling like they do the day after a sleepless night, or like “white static in the brain,” or like coming out of anesthesia. With many it has interfered with their ability to return to work.

A research study in the United Kingdom concluded that in some patients who recovered from a severe infection, “it was as if the brain had aged 10 years almost overnight.”2

How prevalent is post-COVID brain fog?

Overall, it appears that approximately one-third of infected individuals have some sort of post-COVID brain fog. A study in France found that, of 120 patients, one-third had memory loss and one-fourth had other cognitive impairments.2

In a study in a Chicago hospital network of 509 patients, one-third had altered mental function – and of these, 68 percent were unable to handle normal daily activities, like paying bills or cooking a meal.2

An among long haulers, it’s even more prevalent. A new study out of Northwestern University, literally just published today as I finish writing this blog, found that 85 percent of long haulers have lingering neurological symptoms.3 Of those complaining of neurological symptoms, 81 percent complained of brain fog – by far the most prevalent post-COVID neurological/brain symptom.

What causes post-COVID brain fog?

Research on the causes of post-COVID brain fog is still in its infancy. Aside from individuals who actually experience cerebral infarcts (stroke) during active infection, theories about what is causing neurological symptoms in others include an inflammation-associated autoimmune reaction and mitochondrial dysfunction.

Researchers at Brigham and Women’s Hospital in Boston and Johns Hopkins Medicine in Baltimore now have a new theory, and they have evidence to support it. They believe that large cells that are made in the bone marrow called  megakaryocytes – pronounced mega-carry-oh-sights – might be the culprit.4 What are megakaryocytes? They are very large cells (mega) – 10-15 times the size of most other cells. They are produced in the bone marrow to make platelets for blood clotting and wound healing.

The researchers found megakaryocytes in the autopsied brains of five of 15 COVID patients. They compared this to brain tissue from non-COVID autopsies, which contained no megakaryocytes.5 Megakaryocytes are not normally found in the brain – in fact, some research suggests this might be the first time these cells have been found in the brain. Because these cells are very large, it might explain why they present a problem in the brain. It is thought that they slow or block the flow of blood into the capillaries (the tiny blood vessels that connect arteries to veins) of the cerebral cortex, which could result in neurological impairment.

To further support this unique cause for post-COVID cognitive dysfunction, the researchers found no evidence of typical inflammation seen in viral brain infections like encephalitis, and no viral DNA fragments. They also found megakaryocytes in the non-brain tissues of other COVID patients. 

But how did they get there? What signaled these cells to leave the bone marrow and go to the brain? These large cells must travel through the lungs on their way. One theory is that lung-damaged tissue from COVID signaled their release from the bone marrow. Other studies have found significantly increased numbers of megakaryocytes in both bone marrow and the lungs of COVID patients.6 

This process is likely facilitated by inflammation-induced endothelial dysfunction, which has been implicated in severe COVID-related pathologies. The endothelium is the lining of the blood vessels – arteries, veins, and capillaries – and a fully functioning endothelium is important for many aspects of vascular health, from inhibition of excess blood clotting to support for vascular tone. Endothelial dysfunction in COVID-19 can result in increased blood clotting and leaky blood vessels.7 Leaky blood vessels likely allow megakaryocytes to travel to places they don’t belong.

What can you do about it?

It’s too early to know what is going to provide the most benefit for post-COVID brain fog. First some basics:

  1. Exercise to improve circulation to the brain.
  2. Eat a healthy diet – such as the Mediterranean diet, which is full of brain-supportive nutrients like anti-inflammatory omega-3 fatty acids from fish and vascular-supportive flavonoids from a colorful array of fruits and vegetables. Check out some Mediterranean diet recipes.
  3. Get good sleep – nothing says brain fog like a bad night’s sleep.

In addition to the basics, old treatments are being explored for new uses. A study from the University of Alabama, Birmingham (UAB), is testing Constraint-Induced (CI) Movement Therapy.2 CI Movement Therapy has a proven record for post-stroke rehabilitation and has been used for traumatic brain injury, multiple sclerosis, and cerebral palsy. It strengthens a weak limb by restraining the use of stronger limbs. MRI scans at UAB show that CI therapy rewires the brain after two weeks of intensive training, followed by ongoing practice at home.

Now they are turning their attention to cognitive impairment following COVD-19. Although the initial work was in post-stroke patients and limb movement, the researchers are developing a version for cognitive therapy – “CI Cognitive Therapy.” Post-stroke patients with cognitive impairment have been able to resume many of the daily tasks they had been unable to do – return to work, play Scrabble, drive safely, etc.

The training includes 35 hours of computer-based speed-of-processing training and some computer-simulated cognitive tasks, conducted intensely over a 2-week period. Participants also do homework tasks. The researchers are currently recruiting patients who have post-COVID cognitive symptoms and can be reached at 205-934-9768.

As the causes of post-COVID syndrome become better elucidated, the hope is that solutions to resolve these lingering symptoms will also be better understood.

References

  1. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351 [Accessed March 16, 2021]
  2. https://www.uab.edu/reporter/patient-care/advances/item/9410-trial-studying-technique-to-clear-brain-fog-after-covid-19 [Accessed March 16, 2021]
  3. Graham EL, Clark JR, Orban ZS, et al. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 “long haulers.” Ann Clin Transl Neurol 2021 March 23; https://doi.org/10.1002/acn3.51350
  4. https://www.hopkinsmedicine.org/news/newsroom/news-releases/covid-19-story-tip-researchers-may-have-unclouded-the-mystery-of-covid-19-brain-fog [Accessed March 16, 2021]
  5. https://jamanetwork.com/journals/jamaneurology/fullarticle/2776455 [Accessed March 16, 2021]
  6. Roncati L, Ligabue G, Nasillo V, et al. A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients. Platelets 2020;31(8):1085-1089. 
  7. Gavriilaki E, Anyfanti P, Gavriilaki M, et al. Endothelial dysfunction in COVID-19: Lessons learned from coronaviruses. Curr Hypertens Rep 2020;22(9):63.