The APOE ε4 gene variant that puts people at a greater risk of developing Alzheimer’s disease also has a link to COVID-19. According to a study published today (May 26) in The Journals of Gerontology, Series A, carrying two copies of the variant, often called APOE4, makes people twice as likely to develop a severe form of the disease, which is caused by the SARS-CoV-2 coronavirus currently spreading around the world.
David Melzer of Exeter University and colleagues used genetic and health data on volunteers in the UK Biobank to look at the role of the APOE4 variant, which affects cholesterol transport and inflammation. Of some 383,000 people of European descent included in the study, more than 9,000 carried two copies. The researchers cross-referenced this list with people who tested positive for COVID-19 between March 16 and April 26—the assumption being that most such cases were severe because testing at the time was largely limited to hospital settings. The analysis suggested that the APOE4 homozygous genotype was linked to a doubled risk of severe disease, compared with people who had two copies of another variant called ε3.
The result isn’t due to nursing home settings or to a greater likelihood of having a diagnosis of dementia, which none of the 37 people with two copies of APOE4 who tested positive for COVID-19 had. “It is pretty bulletproof—whatever associated disease we remove, the association is still there,” Melzer tells The Guardian. “So it looks as if it is the gene variant that is doing it.”
It is still possible that dementia itself is playing a roll, says David Curtis, an honorary professor at the University College London Genetics Institute, to The Guardian. Some of those 37 people who tested positive have or will develop cognitive issues, but just don’t have a diagnosis currently. “I’m afraid this study does not really convince me that the ApoE e4 allele [gene variant] 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.”
If APOE4 is influencing the course of a SARS-CoV-2 infection, it wouldn’t be the first gene to be fingered as an important factor. Variants in the ACE2 gene that encodes the protein SARS-CoV-2 binds to on host cells, in the HLA genes, and in the genes encoding the ABO blood types have also been linked to COVID-19 susceptibility or severity in preliminary studies.
Tara Spires-Jones, neurodegeneration researcher at the University of Edinburgh who did not participate in the study, tells the publication, “It is possible that the role of ApoE in the immune system is important in the disease and future research may be able to harness this to develop effective treatments.”