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Alarming COVID examine signifies long-term lack of grey matter and different mind tissue

Throughout the pandemic, there has been extensive evidence of brain-related pathologies associated with COVID-19 disease, with “brain fog” and other cognitive defects reported in the vast majority of severe cases, and even otherwise asymptomatic cases of loss of the Sense of taste and smell.

Post-mortem analysis of the nervous system and brain has actually shown that the virus is widespread, although it is still unclear whether mild or asymptomatic cases cause chronic neurological symptoms, as the majority of research has focused on severe and hospitalized patients .

In a research paper recently uploaded to the preprint server medRxiv * by Prof. Gwenaëlle Douaud et al. (June 15, 2021), participants who had taken part in a brain study prior to the outbreak of the COVID-19 pandemic were invited to a series of follow-up tests that showed significant losses of gray matter around the olfactory and gustatory systems in those who had the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were infected.

How was the study conducted?

The UK Biobank is a long-term research and data center that collects and compiles detailed genetic and health information. In the years leading up to the pandemic, thousands of people underwent multimodal brain imaging.

The authors were able to introduce 394 people who had taken part in a previous study by the UK biobank and had become infected with COVID-19 in the meantime, and put together a similarly sized control group who were sorted by gender, age, ethnicity and time between scans (three) years on average.

Three types of structural MRI scans were used: T1 scans, which provide an assessment of brain volume and cortical thickness; T2 fluid-attenuated inversion recovery (FLAIR) scans, which can detect inflammation and tissue damage; and susceptibility-weighted MRI that is sensitive to iron content.

MRI image of the human brain.  Image source: SpeedKingz / Shutterstock

MRI image of the human brain. Image source: SpeedKingz / Shutterstock

Both resting and task function MRI were performed to assess functional connectivity between the brain regions, and blood flow imaging was also used, although the results could not be compared as this procedure was not performed at the first time point.

These scans were used to generate imaging phenotypes (IDP) for participants and compare them to those collected before the pandemic, grouped by age, gender and ethnicity, with those hospitalized for SARS-CoV-2 infection were further identified. of which there were only fifteen.

Influence of SARS-CoV-2 on gray matter volume

Eight significant internally displaced persons were identified among those with COVID-19 who differed from the control group, four of whom were due to the primary or secondary cortical taste and smell areas in the left hemisphere.

The most important results of the longitudinal group comparison.  The three main regions that show a significant loss of gray matter (thickness, volume) between the two time points, especially for COVID patients, are the parahippocampal gyrus, the lateral orbitofrontal cortex and the upper island.  All results were localized to the left hemisphere.  For each region, the IDP spatial region of interest, shown in magenta, overlying the FreeSurfer's average inflated cortical surface;  on the right are the scatter and box plots showing the difference in cortical thickness or volume between the two time points for the 388 controls and 394 COVID patients.  In black circles are the 15 hospitalized COVID patients.  Due to the normalization steps in the IDP preprocessing, all y-axes are arbitrary units that are proportional to the original dimensions.

The most important results of the longitudinal group comparison. The three main regions that show a significant loss of gray matter (thickness, volume) between the two time points, especially for COVID patients, are the parahippocampal gyrus, the lateral orbitofrontal cortex and the upper island. All results were localized to the left hemisphere. For each region, the IDP spatial region of interest, shown in magenta, overlying the FreeSurfer’s average inflated cortical surface; on the right are the scatter and box plots showing the difference in cortical thickness or volume between the two time points for the 388 controls and 394 COVID patients. In black circles are the 15 hospitalized COVID patients. Due to the normalization steps in the IDP preprocessing, all y-axes are arbitrary units that are proportional to the original dimensions.

Three of the IDPs were located around the left lateral orbitofrontal cortex, with the last IDP located in the left superior insula. Each of these three regions showed gray matter loss following infection with SARS-CoV-2, which worsened with disease severity in the fifteen COVID-19 patients known to have been hospitalized.

Other effects were noted in the hospitalized patients, including gray matter loss in regions associated with memory in the left hemisphere and the temporal pole of the right hemisphere.

A vertex-wise longitudinal group comparison shows the thickness of the gray matter.  Threshold map (| Z |> 3) showing the greatest longitudinal differences between the 394 COVID participants and 388 controls.  A more marked reduction in cortical thickness between the two scans in the COVID patients can be observed especially in the left hemisphere in the anterior parahippocampal gyrus (perirhinal cortex), in the anterior and lateral orbital gyrus, the upper insula, the supramarginal gyrus and the anterior cingulate cortex .  In the right hemisphere there is also a marked decrease in the thickness of the gray matter at the temporal pole (also weakly present in the left hemisphere).” Height =”910″  data-src=”https://d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/2021/6/d690v1.jpg”  data-srcset=”https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210618121650/ri/1181/picture/2021/6/d690v1.jpg 1181w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210618121650 /ri/1150/picture/2021/6/d690v1.jpg 1150w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210618121650/ri/950/picture/2021/6/d690v1.jpg 950w, https : //d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210618121650/ri/750/picture/2021/6/d690v1.jpg 750w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210618121650/ ri / 550 / picture / 2021/6 / d690v1.jpg 550w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210618121650/ri/450/picture/2021/6/d690v1.jpg 450w” Sizes =”(min-width: 1200px) 673px, (min-width: 1090px) 667px, (min-width: 992px) calc (66.6vw – 60px), (min-width: 480px) calc (100vw – 40px), calc ( 100vw – 30px)” Title =”A vertex-wise longitudinal group comparison shows the thickness of the gray matter.  Threshold map (| Z |> 3) showing the greatest longitudinal differences between the 394 COVID participants and 388 controls.  A more marked reduction in cortical thickness between the two scans in the COVID patients can be observed especially in the left hemisphere in the anterior parahippocampal gyrus (perirhinal cortex), in the anterior and lateral orbital gyrus, the upper insula, the supramarginal gyrus and the anterior cingulate cortex .  In the right hemisphere there is also a marked decrease in the thickness of the gray matter at the temporal pole (also weakly present in the left hemisphere).” Width =”1181″/></p>
<p><span style=A vertex-wise longitudinal group comparison shows the thickness of the gray matter. Threshold map (| Z |> 3) showing the greatest longitudinal differences between the 394 COVID participants and 388 controls. A more marked reduction in cortical thickness between the two scans in the COVID patients can be observed especially in the left hemisphere in the anterior parahippocampal gyrus (perirhinal cortex), in the anterior and lateral orbital gyrus, the upper insula, the supramarginal gyrus and the anterior cingulate cortex . In the right hemisphere there is also a marked decrease in the thickness of the gray matter at the temporal pole (also weakly present in the left hemisphere).

The authors claim several advantages over similar studies based on a comparison between COVID-19 patients and a control without MRIs before the pandemic outbreak, which has allowed them to perform a much more refined analysis.

For example, comparing the COVID-19 and non-COVID groups showed a significant difference in volume of the thalamus, with those who had gray matter reduction from the virus.

Including the pre-pandemic results, however, showed that the same person had little difference in amounts after being infected with SARS-CoV-2 and that those infected with the virus had a smaller thalamus on average.

Whether this played a role in the likelihood of infection with SARS-CoV-2 is unclear and requires extensive follow-up studies.

The parahippocampal gyrus, the lateral orbitofrontal cortex, and the upper islet of the left hemisphere are the earliest cortical relays of the olfactory and gustatory systems and were the most heavily affected regions of the brain during COVID-19 infection.

The olfactory bulb has been thought to be the entry point of SARS-CoV-2 into the central nervous system, and the magnitude of the effect at these sites could support this hypothesis.

Many of the results observed here are strikingly similar to those associated with Alzheimer’s disease and other forms of dementia. This has raised concerns that the long-term consequences of COVID-19 could include these disruptions.

*Important NOTE

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, that guide clinical practice / health-related behavior or are treated as established information.

Journal reference:

  • Brain imaging before and after COVID-19 in the UK Biobank, Gwenaëlle Douaud, Soojin Lee, Fidel Alfaro-Almagro, Christoph Arthofer, Chaoyue Wang, Frederik Lange, Jesper LR Andersson, Ludovica Griffanti, Eugene Duff, Saad Jbabdi, Bernd Taschler, Anderson Winkler, Thomas E. Nichols, Rory Collins, Paul M. Matthews, Naomi Allen, Karla L. Miller, Stephen M. Smith, med.Rxiv, 06.11.2021.21258690; doi: https://doi.org/10.1101/2021.06.11.21258690, https://www.medrxiv.org/content/10.1101/2021.06.11.21258690v1

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