ArticleActa neuropathologica communications2021
APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Intracranial hemorrhages in patients with COVID-19: a systematic review of the literature, regarding six cases in an Amazonian population.Arquivos de neuro-psiquiatria · 2023Pooled it
- SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature.Acta neuropathologica communications · 2023Pooled it
- ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.Journal of translational medicine · 2023Pooled it
- Genetics of COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review.Annals of clinical and translational neurology · 2022Pooled it
- Lack of association between APOE genotypes and COVID-19 in a black South African cohort.Scientific reports · 2026Article
- Intersection of COVID-19 and Alzheimer's Disease: Genetic Insights and Neuropathological Consequences.Biochemical genetics · 2026Review
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1.Expert review of clinical pharmacology · 2026Review
- Cerebrospinal fluid and frontal cortex TMPRSS2 and ACE2 protein levels differ in Down syndrome and Alzheimer's disease.Acta neuropathologica communications · 2026Article
- Modest Neurodevelopment Impacts of <italic>APOE4</italic> in a Human Brain Organoid Model of Low-Grade SARS-CoV-2 Infection.Developmental neuroscience · 2026Article
- Post-Covid Alzheimer and Its Remediation via PROTACs Therapy: A Comprehensive Review.Health science reports · 2026Article
- Running out the clock: Circadian rhythm dysfunction in cognitive disease.International review of neurobiology · 2026Review
- Agitation, Alzheimer's disease, and autophagy: mechanistic insights into aging pathways, gut microbiome, and artificial intelligence.Frontiers in immunology · 2026Review
- ApoE4 Homozygosity Is Associated With Increased Microglia Activation in Fatal COVID-19.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- The impact of APOE4 on neurological symptoms after exposure to K. brevis neurotoxin.Environmental toxicology and pharmacology · 2025Article
- Effects of West Nile virus on behavioral and cognitive performance, cortical Aβ pathology, viral loads, and immune measures of middle-aged NL-G-F/E3 and NL-G-F/E4 mice.Frontiers in aging neuroscience · 2025Article
- COVID-19 and the impact on Alzheimer's disease pathology.Journal of neurochemistry · 2024Review
- Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.Journal of neuroinflammation · 2024Review
- Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes.Open biology · 2024Article
- Differential Cytokine Responses of APOE3 and APOE4 Blood-brain Barrier Cell Types to SARS-CoV-2 Spike Proteins.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.