Dementia-linked Gene Could Raise Risk of Developing Severe COVID-19, Study Suggests

People with a gene which increases the risk of developing dementia could be more likely to have a severe case of COVID-19, according to a study.

The paper published in the Journal of Gerontology: Medical Sciences linked carrying two faulty copies of the APOE gene to a two-fold risk of having severe COVID-19 from the baseline.

There are three different versions of the APOE gene: e2, e3, and e4. E3 is the most common. Past research has shown that e4 raises the risk of developing dementia, while two copies of e4e4 is linked with a 14-fold risk of developing Alzheimer's in those of European descent compared with carriers of e3e3 in this group.

For this latest project, researchers looked at data on 322,948 people from the ongoing UK Biobank study, aged between 48-86 years old. 9,022 participants had both faulty genes; 90,469 had e3e4, and 223,457 had the most common combination of e3e3.

Coronavirus test results for participants in England were available from March 16 to April 26, 2020. At this time, mainly hospital patients in the U.K. were tested and therefore more likely to have a severe COVID-19 case, the team highlighted. Of the total participants, 622 tested positive for COVID-19 in lab tests, according to the researchers. Of those 37 had e4e4.

Those with e4e4 were twice as likely to test positive for coronavirus compared to those with e3e3. The link was similar when the team removed participants with diseases associated with e4 and linked to COVID-19 severity, including high blood pressure, heart disease, and type 2 diabetes.

"Further investigation is needed to understand the biological mechanisms linking APOE genotypes to COVID-19 severity," wrote the authors.

Co-author Dr. Chia-Ling Kuo of the University of Connecticut School of Medicine commented in a statement: "This is an exciting result because we might now be able to pinpoint how this faulty gene causes vulnerability to COVID-19. This could lead to new ideas for treatments.

"It's also important because it shows again that increasing disease risks that appear inevitable with ageing might actually be due to specific biological differences, which could help us understand why some people stay active to age 100 and beyond, while others become disabled and die in their sixties."

Lead author David Melzer, professor of Epidemiology and Public Health, said in a statement: "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."

Fiona Carragher, director of research and influencing for the U.K.-based care and research charity Alzheimer's Society who was not involved in the paper, told Newsweek the research is in its early stages. "Other factors may contribute, so it is difficult to draw firm conclusions at this stage," Carragher said.

David Curtis, honorary professor at the UCLGenetics Institute who was not involved, commented in a statement: "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. 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."

John Gallacher, professor of cognitive health at Oxford University who also didn't work on the study, said: "This paper provides strong evidence of a link between genetic risk for Alzheimer's disease and genetic risk for COVID-19. This suggests one or more common mechanisms underlying both conditions.

"A common mechanism would indicate increased risk of COVID-19 in those with Alzheimer's disease, but not that Alzheimer's disease itself is a direct cause of COVID-19 susceptibility. However, Alzheimer's disease may be an indirect cause.

"For example, increased frailty in those with Alzheimer's disease would imply reduced resistance to infection and increased disease severity. Increased risk and increased frailty are reasons enough to consider those with dementia to be a high risk group for COVID-19."

Dr. Carol Routledge, director of research at the charity Alzheimer's Research UK also didn't work on the study. She said in a statement: "We don't yet know how this Alzheimer's risk gene might make people more susceptible to the virus. Despite the large study group, only 37 people with the risk gene tested positive for COVID-19, and we must be careful about the conclusions we draw from such small numbers.

"These findings will need to be followed up with further research to see if this link could present avenues for new treatments."

Routledge also pointed out the findings may not relate to other groups as the study analyzed data from participants with European ancestry.

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