APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study.
Adult
Aged
Apolipoprotein E4
/ genetics
Autopsy
Biological Specimen Banks
COVID-19
/ complications
Cerebral Hemorrhage
/ diagnosis
Cohort Studies
Female
Finland
/ epidemiology
Genetic Association Studies
/ methods
Heterozygote
Humans
Male
Mental Fatigue
/ diagnosis
Microvessels
/ pathology
Middle Aged
Patient Acuity
Prospective Studies
Risk Factors
Young Adult
Post-Acute COVID-19 Syndrome
APOE4
Biobank
Brain microhaemorrhage
COVID-19 sequelae
Neuropathology
Post-viral fatigue
SARS-CoV-2
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
23 12 2021
23 12 2021
Historique:
received:
27
10
2021
accepted:
02
12
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
6
1
2022
Statut:
epublish
Résumé
Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.
Identifiants
pubmed: 34949230
doi: 10.1186/s40478-021-01302-7
pii: 10.1186/s40478-021-01302-7
pmc: PMC8696243
doi:
Substances chimiques
Apolipoprotein E4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
199Subventions
Organisme : Terveyden Tutkimuksen Toimikunta
ID : 341007
Organisme : Terveyden Tutkimuksen Toimikunta
ID : 336439
Organisme : Terveyden Tutkimuksen Toimikunta
ID : 335527
Organisme : Helsingin ja Uudenmaan Sairaanhoitopiiri
ID : TYH2021310
Informations de copyright
© 2021. The Author(s).
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