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Reduction of cerebral cortex after Corona infection demonstrated in humans

Some time ago, I reported in two blog posts about the neurological consequences of a SARS-CoV-2 infection. Inflammatory changes in the brain have been demonstrated, which are accompanied by fatigue and reduced performance and can last for months in the sense of a long covid syndrome. Today, I would like to present a study that used imaging techniques (magnetic resonance imaging, MRI) to demonstrate the effects of corona disease on the brain substance itself.

Work has been ongoing in England since 2006 on a biobank that includes a large number of volunteers (more than 40,000 individuals over the age of 45 in 2022). The primary goal of this systematic data collection over a long period of time is to determine the proportion of genetic predisposition or environmental exposure responsible for a wide variety of diseases. In addition to interviews and laboratory tests, the brains of the patients are scanned. Thus, for the first time, cerebral MRI data before and after COVID-19 disease could be collected in the same individuals for the study and compared to a control group of uninfected individuals. The mean interval between the two images was 3 years. A total of 785 subjects were included in the study, 401 of whom had experienced SARS-CoV-2 disease during this time (384 subjects formed the control group).

The publication in the renowned journal Nature (Douaud et al., see reference below) now clearly showed that gray matter, i.e. cortical areas with high nerve cell density, is slightly reduced by covid infection (the control group was not affected). This reduction affects 2-3% of cortex volume with overall reduced brain mass. The difference is particularly evident in older patients over 70 years of age. Primarily affected are the inferior frontal lobe (the orbitofrontal cortex above the orbits) and the medial (inferior) temporal lobe, the parahippocampal gyrus. The infection thus preferentially affects the limbic system, i.e. the areas responsible for emotions and memory. It also fits that in accompanying neuropsychological examinations of these patients the loss of cognitive abilities was clearly detectable (by about 10 intelligence quotient points in hospitalized patients). Interestingly, however, brain matter and mental abilities also decrease in those subjects who had only undergone a mild corona infection, i.e. who had not been hospitalized.

Comparison of the cerebral cortex of subjects with SARS-CoV-2 infection (Cases, yellow line) or without Covid-19 disease (Controls, blue line). Left (a) shows the decrease in the parahippocampal gyrus area, right (b) in the orbitofrontal gyrus area as a function of age. The differences become more pronounced with increasing age (modified Fig. 1 from Douaud G et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, 2022, 604: 697-707).

The present study is unique in that brain scans were obtained from a large number of patients not only after Covid disease but also before infection. This made it possible to exclude existing previous damage and prior changes in the brain. Furthermore, both groups were almost completely matched, i.e. differences in gender, age, ethnicity, blood pressure, diabetes, weight, alcohol or nicotine consumption and socioeconomic status were eliminated.

So how do the observed changes come about? It has been known for some time that SARS-CoV-2 viruses enter the olfactory bulb, the bulbus olfactorius, and thus the limbic part of the brain via the inflamed olfactory epithelium. The omission of olfactory input (the loss of smell) alone may have led to substance reduction. However, the viruses also reach other parts of the brain via blood vessels and activate a large number of inflammatory cells, especially microglial cells. Future studies must show whether neurodegeneration actually occurs as a result. It is possible that the morphological changes are reversible. After all, it could be that the affected cortex areas recover (which is unlikely in the case of neuronal damage, since nerve cells can no longer divide). In Covid-19-infected rhesus monkeys, neuronal demise has already been demonstrated, especially in animals suffering from diabetes mellitus.

The findings of the Biobank study are supported by two other recent studies (Hampshire et al. and Qureshi et al.) that looked for neurological disorders in a large number of Covid patients. They showed that about 3% of more than 10,000 patients with severe SARS-CoV-2 pneumonia develop new-onset dementia after one month. Overall, the risk of dementia is increased by 30% after Covid pneumonia (compared with pneumonia from other causes). On average, cognitive abilities in Covid 19 survivors declined 6-10 months after infection by a factor equivalent to the decline in intelligence between 50 and 70 years of age. Therefore, a long-term persistent neurodegenerative component after severe illness should be assumed and Covid-19 vaccination should continue to be strongly recommended.


Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, 2022, 604: 697-707

Hampshire A, Chatfield DA, Mphil AM, Jolly A, Trender W, Hellyer PJ, et al. Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort. eClinicalMedicine, 2022, 47:101417

Qureshi AI, Baskett WI, Huang W, Naqvi SH, Shyu C-R. New-onset dementia among survivors of pneumonia associated with severe acute respiratory syndrome coronavirus infection. Open Forum Infect Dis, 2022, 9(4)

Image credit: iStock/Jian Fan and iStock/dusanpetkovic


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