The first major study to compare brain scans of people before and after they catch Covid has revealed shrinkage and tissue damage in regions linked to smell and mental capacities months after subjects tested positive.
It comes as the largest study to date of the genetics of Covid-19 identified 16 new genetic variants associated with severe illness, and named a number of existing drugs that could be repurposed to prevent patients from getting severely ill, some of which are already in clinical trials.
Together, these studies shed new light on the biological mechanisms that underpin the disease.
In the brain study, researchers at the University of Oxford studied 785 people aged between 51 and 81 who had received brain scans before and during the pandemic as part of the UK Biobank study. More than half of them tested positive for Covid between the two scans.
Compared with 384 uninfected control subjects, those who tested positive for Covid had greater overall brain shrinkage and more grey matter shrinkage, particularly in areas linked to smell. For example, those who had Covid lost an additional 1.8% of the parahippocampal gyrus, a key region for smell, and an additional 0.8% of the cerebellum, compared with control subjects.
Disrupted signal processing in such areas may contribute to symptoms such as smell loss. Those who were infected also typically scored lower on a mental skills test than uninfected individuals. Lower scores were associated with a greater loss of brain tissue in the parts of the cerebellum involved in mental ability.
The effects were more pronounced in older people and those hospitalised by the disease, but still evident in others whose infections were mild or asymptomatic, the research suggested, which was published in the journal Nature.
Further scans are needed to determine whether these brain changes are permanent or partially reversible.
“The brain is plastic, which means that it can re-organise and heal itself to some extent, even in older people,” said Prof Gwenaëlle Douaud at the University of Oxford.
In separate research also published in Nature, researchers led by Dr Kenneth Baillie, a consultant in critical care medicine at the University of Edinburgh, sequenced the genomes of 7,491 Covid patients admitted to intensive care units in the UK. Researchers compared their DNA with that of 48,400 people who had not been infected, plus the DNA of a further 1,630 people who experienced mild Covid.
The study identified 16 new genetic variants associated with admission to intensive care, including genes implicated in blood clotting, the immune system and the intensity of inflammation.
It also confirmed the involvement of seven other genes that the team identified in earlier studies, and which contributed to the rheumatoid arthritis drug baricitinib being tested on Covid patients. Data published last week showed that it reduced the risk of death from severe Covid by about a fifth, demonstrating “proof of principle that we can find new treatments using genetics”, Baillie said.
Among the new variants identified is a small change in GM-CSF, a protein that helps to activate immune cells in the lungs after infection. A drug targeting this gene, otilimab, is being tested in people with Covid. “To have a genetic signal close to this gene gives us more confidence that this is a valid target,” said Baillie.
Others included variations in genes that control the levels of a central component of blood clotting – known as Factor VIII – which is disrupted in the most common type of the inherited bleeding disorder haemophilia. Abnormal clotting in response to Covid could result in reduced oxygen supply to critical organs, Baillie explained.
“These results explain why some people develop life-threatening Covid-19, while others get no symptoms at all. But more importantly, this gives us a deep understanding of the process of disease and is a big step forward in finding more effective treatments,” he added.
“It is now true to say that we understand the mechanisms of Covid better than the other syndromes we treat in intensive care in normal times – sepsis, flu, and other forms of critical illness. Covid-19 is showing us the way to tackle those problems in the future.”