It is wrong to think that it is OK for coronavirus transmission to continue at such levels. There is more and more evidence of significant persistent changes in the brain even among people with relatively mild COVID-19.

First published in June 2021.

There is more and more evidence accruing that SARS-CoV-2 causes significant persistent effects on the brain.

We now have multiple strands supporting this:

  • long-term symptoms-brain fog, memory loss;
  • higher risk of stroke/neuro diseases;
  • structural brain changes;
  • virus persistence in brain.

We know that SARS-CoV-2 is neuro-invasive. This means that it enters the brain. We think this is through the olfactory nerve (the nerve that helps us smell) through the nose. This has been shown in mice, hamsters and directly in humans in autopsies.

Detection of SARS-CoV-2 in deceased individuals with COVID-19 in anatomically distinctly mapped oro- and nasopharyngeal as well as CNS regions. | Nature

Replicating SARS-CoV-2 has also been shown to persist in neuro-epithelium (olfactory nerves in the nose) for up to 6 months among people who have recurrent or persistent loss of smell.

Neurological symptoms are significant among people post-COVID, and they persist for long periods of time, even after other symptoms recover. ONS data shows that problems with concentration, memory, brain fog, loss of smell/taste are common persistent symptoms after infection.

Number of people with self-reported long COVID by symptom, UK, 2 May 2021

Symptom based surveys have consistently shown that neurological symptoms are more likely to arise later, and persist over time, and symptom clusters that have neurological symptoms generally also correlate with poorer day to day functioning.

Two clusters of ongoing symptoms and acute symptoms among these clusters. | medRxiv

A Lancet Psychiatry study showed that neurological and psychiatric diagnosis were very common at 6 months after COVID-19, and the risk for psychiatric disorders, strokes, dementia, muscle disorders was significantly higher, even in those not hospitalised.

There have been earlier studies that have looked at cognitive decline following hospitalisation with COVID-19 suggesting significant reduction after hospitalisation. These studies have been limited by not having measurements pre-COVID-19 to establish that this was the cause.

This is addressed now in a study by UK Biobank. This is a cohort of generally healthy people who have had many measurements done as part of the study. Around 40,000 people have had brain imaging done for research purposes before the COVID-19 pandemic.

Of the people who have had their second MRI brain scan in the Biobank study, some of them developed COVID-19 before the second scan. We can compare brain changes between those infected to those not infected by comparing the change in brain structure between the two scans.

394 people who were COVID-19 positive (only 15 of these were hospitalised) were imaged after COVID-19 was diagnosed. These were compared with 388 controls (not diagnosed with COVID-19). Both groups had MRI scans done before the pandemic at baseline.

They were compared for volume and thickness in certain areas of the brain. Cases and controls were matched for age, sex, ethnicity and the time between the baseline and repeat MRI scan to ensure any difference in change in brain structure between the two groups was not down to these.

The groups were well matched. Age was between 47-80 (mean age ~59). Similar blood pressure, prevalence of diabetes and BMI. As mentioned, most of the COVID group was people who were infected and tested in the community with non-severe COVID-19.

Main demographics of the COVID patients and controls. | medRciv

Most of the patients had been diagnosed in October 2020 or after, and the duration between infection and scan varied accordingly. Mean duration was 4.5 months post COVID-19.

Main clinical information available for the COVID patients. | medRciv

The study found significant reduction in grey matter in certain parts of the brain – especially those associated with smell, and memory.

Of note: these are changes in a population of people who mostly had mild COVID symptoms – greater reduction from baseline in those with COVID.

Hypothesis-driven olfactory and gustatory approach: longitudinal group comparison results. | medRciv

While correlation isn’t causation, the fact that these people were imaged at baseline before COVID-19 – allowing to compare to a group not infected with COVID-19 to look at difference in decline in grey matter after COVID compared to those who were not infected – makes it strong.

Remember, these groups were also the same age, had the same interval between scans, and many similar characteristics, making it unlikely this decline is down to something other than COVID-19.

This is very concerning. We are seeing evidence of significant changes in the brain even among people with relatively mild COVID-19. This study was in 46-80 year olds, and many would have been healthy.

We urgently need to understand the impact of COVID-19 in younger age groups too.

This isn’t just one study that suggests a link between SARS-CoV-2 and neurodegenerative disease. There have been several care reports of early-onset parkinsonism after SARS-CoV-2 infection, highlighting possible links with neuro-degenerative disease.

Does this happen with other viruses? Yes, many viruses invade and affect the brain: herpes viruses, Zika virus, measles, polio and of course, the Spanish flu (encephalitis lethargica as immortalised in Awakenings). Other coronaviruses are known to invade the brain too.

This has been concerning for a while, but recent reports show us that ignoring this will come at a huge cost. We need to stop focusing on hospitalisations and deaths as the only outcome, and stop thinking that it is OK for transmission to continue at such levels. It is not.

This is the sort of thinking that will possibly leave thousands with chronic debilitating neurological illness, as well as other impacts of long COVID. By the time our scientific community and government are satisfied that there is irrevocable evidence, it will be much too late.

While I am not a neuroscientist, I have worked with Dr Hisham Ziauddeen, a psychiatrist and neuroscientist, to make sure my interpretation of the UK Biobank study is correct. I have seen several non-experts comment on possible limitations of the study, and so wanted to ensure that I had sought an expert perspective.

Conclusion: This is a robust study that shows significant change in brain structure, and thinning of grey matter in memory, smell and taste associated brain regions post-COVID-19. We should be concerned.

This is not a virus we should be happy to expose anyone to. 

Going Further:


Dr Deepti Gurdasani, Senior Lecturer in Epidemiology, Statistical Genetics, Machine Learning, Queen Mary University of London.


[This piece was first published as a Twitter thread and turned into the above article on 21 June 2021 with the purpose of reaching a larger audience. It has been minorly edited and corrected, and published with the author’s consent. | The author of the tweets writes in a personal capacity.]

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