Bengaluru: Scientists at the University of Oxford’s Wellcome Centre for Integrative Neuroimaging have found changes in the brain structure of Covid patients, including those who experienced mild infection.

In a study, the authors looked at brain MRI scans of participants, which included healthy controls. The team also had access to all the participants’ brain scans from before the onset of the pandemic.

Conducted on 785 participants from the biomedical database UK Biobank, the study observed that among those who had been infected with Covid, there was a greater reduction in grey matter thickness, greater tissue damage in regions of the brain connected with the olfactory or smell complex, and an overall shrinkage in size of the brain.

The scientists noted that the participants who showed changes in their brain scans also showed larger cognitive decline between two consecutive post-Covid scans, spaced apart. These effects were also observed in those who had experienced only mild Covid and hadn’t been hospitalised.

Their findings were published in the journal Nature Monday.

The authors state that the findings from the paper could be hallmarks of degenerative spread of Covid via the olfactory pathways to the brain, either from loss of sensory input from anosmia (loss of smell) or by inflammation of the spinal cord and brain.

The authors caution that the implications of the visible brain changes are unclear, and the highly plastic and flexible human brain could still recover or even already be in the process of recovery for these patients.

The findings do not necessarily imply that Covid will affect memory or cognition in the long term, they said, and it is also unclear if the changes will affect a person’s quality of life going forward.

“Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up,” wrote the team of scientists in the paper.

Also read: UK scientists identify genetic factors behind severe Covid symptoms

Study design and conclusion

For the study, the scientists recruited 785 participants from UK Biobank, a large-scale database holding genetic and health information of over 5,00,000 UK citizens for 15 years. The database held MRI brain scans of all recruits from before the onset of the pandemic, and has also been releasing data from Covid re-imaging studies on a rolling basis.

Of the participants, 401 had contracted various stages of Covid, while 384 were healthy controls who were matched for age, sex, ethnicity, and time elapsed between two scans. All participants were aged between 51 and 81.

Of the patients, 15 had been hospitalised and two received critical care. These patients were older men with increased severity of comorbidities.

The later scans showed differences between patients and controls in areas of the brain that are functionally connected to the primary olfactory cortex, a portion of the cerebral cortex that is involved in the sense of smell.

They also found reduction in the thickness of grey matter in various regions, when compared to controls. Grey matter consists of neurons, as well as synapses, which help neurons pass electrical signals to each other. The cells in grey matter are involved in controlling the movement of muscles, sensory input, pain, motion and vibrational input, relaxation of muscles for metabolic functions, changes to body organs during physiological responses, and more.

Grey matter is one of the major components of the central nervous system and can undergo changes due to lifestyle, substance use, and pregnancy.

The authors found that the most significant reduction in grey matter occurred in the regions connected to olfactory processing.

The patients’ brains also exhibited evidence of tissue damage in regions associated with the olfactory complex. While the disease could have had a direct effect on this region (without the virus entering the central nervous system), it is also likely that the cells here died due to lack of use when the patients suffered from persistent anosmia or loss of smell.

The largest changes were noted in the olfactory system, dealing with smells, and the limbic systems, which are involved in core behavioural and emotional responses required for survival.

Grey matter reduction also occurred in the parahippocampal gyrus, the part of the brain associated with memory and recall.

The authors also found that parts of the brain showed an overall reduction in volume and size.

To confirm that the effects on the brain were from Covid and not pneumonia or influenza, the team performed additional comparisons with groups of participants who had contracted pneumonia and influenza, but not Covid.

Cognitive decline

The study adds to the growing body of research into long Covid, and is one of the earliest definitive ones to delve into how long Covid impacts the body and brain.

​​Persisting symptoms of long Covid weeks and months after infection have been primarily known to include fatigue, shortness of breath, brain fog, loss of concentration, disruption of sleep, increased anxiety, and reduced cognitive function.

​​It is the first study to compare changes in the brain over time after Covid, with brain scans before Covid.

The authors found that those who had suffered from Covid had difficulty performing cognitive tasks like they used to. They were given tasks like measuring memory, matching pairs, and more, which are often used to differentiate between healthy ageing and dementia by measuring attention and efficiency.

The scientists saw that participants took a significantly longer time to complete numeric and alphanumeric trail-making tests, which involved linking numbers and letters alternately in a trail.

With cognition tests, the team also found that people in their 50s and 60s performed similarly, but differences shot up significantly after that.

On average, participants who had been infected showed greater cognitive decline between two scans. This is associated with atrophy, or degradation from lack of use, of parts of the cerebellum, which is involved in cognition.

Why such changes are caused in the brain is as yet undetermined. The scientists theorise that it could either be from inflammation of the spinal cord, or sensory deprivation leading to not using the olfactory complex.

(Edited by Nida Fatima Siddiqui)

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