Dementia gene linked to an increased susceptibility to severe COVID-19

A gene variant linked to Alzheimer's disease has been shown to increase the risk of developing severe COVID-19 symptoms. 

Researchers at the University of Exeter Medical School and the University of Connecticut School of Medicine reported the link after analysing data from the UK BioBank, a research platform that has collected genetic and health data from 500,000 volunteers aged between 48 and 86. 

'Several studies have now shown that people with dementia are at high risk of developing severe COVID-19. This study suggests that this high risk may not simply be due to the effects of dementia, advancing age or frailty, or exposure to the virus in care homes. The effect could be partly due to this underlying genetic change, which puts them at risk for both COVID-19 and dementia,' said Professor David Melzer who led the team.

The team focused on a faulty variant of the APOE gene - termed ApoE e4 - which is known to affect cholesterol levels and inflammatory processes and increases the risk of Alzheimer's up to 14-fold.

The study found that 2.36 percent of the approximately 383,000 people of European descent included in the study carried two copies of the ApoE e4 variant. 

However, among the participants who had been hospitalised after testing positive for COVID-19 between 16 March and 26 April 2020 they found that 5.13 percent had two copies of the ApoE e4 variant, leading them to suggest the faulty gene is linked to a doubled risk of severe disease.

The same team previously discovered that people with diagnosed dementia are three times more likely to get severe COVID-19. It had been speculated that this might be due to the high prevalence of the virus in care homes, but the authors think this most recent work now suggests that a genetic factor may be at play. 

An independent genetic link is also possible given that none of the COVID-19 positive patients involved in the study actually had a diagnosis of dementia – just an increased risk of it. However, the authors cautioned that further work is still needed to strengthen their findings and understand the biological mechanisms linking ApoE variants to COVID-19 severity. 

Professor David Curtis from the University College London Genetics Institute raised caution about the results as it is possible that dementia itself – rather than the underlying genes – is still playing a role as some study participants may have undiagnosed dementia.

'I'm afraid this study does not really convince me that the ApoE e4 allele is really an independent risk factor for severe COVID-19 infection,' he told the Guardian. 'I would want to see this tested in a sample where dementia could be more confidently excluded, perhaps a younger cohort. I am sure additional data will soon emerge to illuminate this issue.'

The research was published in the Journal of Gerontology: Medical Sciences.