Brain Fog - research update

“We know that COVID-19 can disrupt multiple body systems but the effects of the virus and the body’s response to COVID-19 infection on the brain, spinal cord, nerves, and muscle can be particularly devastating, and contribute to persistence of disability even after the virus is cleared,”

- Dr Barbara Karp, MD, program director at the NIH’s National Institute of Neurological Disorders and Stroke.

COVID-19–related neurological problems include headaches, fatigue, cognitive difficulties, stroke, pain, and sleep disorders.

Long Covid sufferers identify especially with crushing fatigue, recurrent headaches, sleep disorders and brain fog.

As a quick reminder brian fog is described as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, short term memory loss or a haziness in thought processes. In severe cases delirium and psychosis. These symptoms can persist for many months after the initial infection.

In a recent paper "Persistent neurological symptoms and cognitive dysfunction in non-hospitalised Covid-19 Long Haulers", printed in The Annals of Clinical and Translational Neurology, the 10 most common neurological complaints among the study participants (70% women, average age 43) were:

  • Cognitive dysfunction - reported by 81%

  • Headache - 68%

  • Numbness or tingling - 60%

  • Disorder of taste - 59%

  • Disorder of smell - 55%

  • Muscle pain - 55%

  • Dizziness - 47%

  • Pain - 43%

  • Blurred vision - 30%

  • Tinnitus (ringing in the ears) - 29%

In today's blog I wanted to highlight the new research out there trying to shed a light on these neurological complications of Covid-19.

1. New Research - Collecting Data About COVID-19–Related Brain Symptoms

The National Institutes of Health (NIH) in the US is planning to launch a new database and biobank to collect information from clinicians about neurological problems associated with COVID-19. Called the NeuroCOVID Project the aim is to gain insight into how common these neurological problems are. Clinicians can submit information about neurological symptoms, co-morbidities, disease course, complications, and outcomes to the NeuroCOVID Project databank. The databank will be used to assess new neurological COVID-19 complications as well as potential exacerbation of pre-existing neurological conditions. In addition, clinicians can submit specimens, such as blood, plasma, cerebrospinal fluid, and tissue, to the project’s biobank.

2. New research - Cytokines found in the Cerebrospinal fluid in patients with COVID-19 delirium

In New York a study was done as to why patients hospitalised with COVID-19 were experiencing severe delirium - an acute confusional state.

In this study Dr Wilcox and fellow researchers screened the cerebrospinal fluid (CSF) of 18 cancer patients who were experiencing encephalopathy - an acute confusional state caused by being been infected with the SARS-CoV-2 virus.

Initially, it was suspected that an ongoing viral infection might be the cause of their brain fog symptoms, but microbiological analysis of fluid taken in lumbar punctures did not reveal any sign of the virus in the CSF fluid. However they did find high level of cytokines in the CSF.

Cytokines as proteins found in the body that are involved with signalling in the immune system.

In some cases of COVID-19, an over-production of these molecules results in the cytokine storm, which can cause excessive inflammation which can damage vital organs and can be fatal. The thinking is that the flood of these inflammatory chemicals in the immune system seeps into the brain, producing symptoms of delirium in these patients.

So COVID infections are known to cause inflammation in the body it's also possible that this process causing inflammation in the brain which can cause the brain to not function normally.

The findings here suggest that anti-inflammatory drugs might be helpful in mitigating brain fog in patients.

Note- many of us who have started anti-inflammatory diets have had some benefit also.

3. New Research - Autoantibodies found in in COVID-19 patients with neurological symptoms

So patients with delirium and other neurological symptoms are found to have cytokines and inflammation in their CSF.

In a recent study blood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including muscle twitching, visual disturbance, delirium, and epileptic seizures, were analyzed for autoantibodies.

Autoantibodies are antibodies which recognise parts of our own body. They found autoantibodies in the CSF which were able to bind to many parts of the brain:

Vessel endothelium - the blood vessels supplying oxygen and nutrients to the brain

Basal ganglia - movements, motor learning, executive functions and behaviours (please see previous post on executive dysfunction) and emotions.

Hippocampus - learning and memory

Olfactory bulb - smell and taste.

I think for many of us with ongoing cognitive dysfunction this research really rings true. A utoantibodies may now explain some aspects of neurological symptoms in COVID-19 and could be used to guide immunotherapy in selected cases.

4. New Research - Megakaryocytes found in brains of Covid-19 patients

Large cells, known as megakaryocytes, have been found in the brains smallest blood vessels of Covid-19 victims by Professor Nauen a pathologist at the Johns Hopkins University School of Medicine.

This has never been seen before and maybe specific to Covid-19 infections. He said:

"If these massive cells are indeed blocking blood flow to the brain, it would starve the brain of enough oxygen and nutrients to work at full capacity. Not precisely delivering oxygen based on time and need could be leading to impaired cognitive function, like a brain fog picture".

The next question Nauen wants to answer how these megakaryocytes are getting there and what sort of communication the cells are using in the process?

5. New Research - COVID-19 attack on the brain triggers severe disease in mice

Georgia State University biology researchers have found that infecting the nasal passages of mice with the virus that causes COVID-19 led to a rapid, escalating attack on the brain that triggered severe illness, even after the lungs were successfully clearing themselves of the virus.

The lead researcher Professor Kumar has said:

"Our thinking that it's more of a respiratory disease is not necessarily true. Once it infects the brain it can affect anything because the brain is controlling your lungs, the heart, everything. The brain is a very sensitive organ. It's the central processor for everything."

The study, published by the journal Viruses, assessed virus levels in multiple organs of the infected mice. A control group of mice received a dose of sterile saline solution in their nasal passages.

Initial studies involving mice focused on the animals' lungs and did not assess whether the virus had invaded the brain. The research team found that virus levels in the lungs of infected mice peaked three days after infection, then began to decline. However, very high levels of infectious virus were found in the brains of all the affected mice on the fifth and sixth days, which is when symptoms of severe disease became obvious, including difficulty in breathing, disorientation and weakness.

The study found virus levels in the brain were about 1,000 times higher than in other parts of the body.

The findings could help explain why some COVID-19 patients seem to be on the road to recovery, only to rapidly relapse and die. The research suggest the severity of illness and the types of symptoms that different people experience could depend not only on how much virus a person was exposed to, but how it entered their body.

The nasal passages provide a more direct path to the brain than the mouth. And while the lungs humans are designed to fend off infections, the brain is poorly equipped to do so. Once viral infections reach the brain, they trigger an inflammatory response that can persist indefinitely, causing ongoing damage.

"The brain is one of the regions where virus likes to hide, because it cannot mount the kind of immune response that can clear viruses from other parts of the body. That's why we're seeing severe disease and all these multiple symptoms like heart disease, stroke and all these long-haulers with loss of smell, loss of taste, fatigue, brain fog. All of this has to do with the brain rather than with the lungs.”

Kumar said that COVID-19 survivors whose infections reached their brain are also at increased risk of future health problems, including auto-immune diseases, Parkinson's, multiple sclerosis and general cognitive decline. I find this last statement especially scary as one still suffering at 12 months with cognitive dysfunction.


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