APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study

• DOI: 10.1186/s40478-021-01302-7
• Publication Date: 2021-12-23T10:19:08Z
• Authors: Samu N. Kurki; Jonas Kantonen; Karri Kaivola; Laura Hokkanen; Mikko I. Mäyränpää; Henri Puttonen; ; Juha Martola; Minna Pöyhönen; Mia Kero; Jarno Tuimala; Olli Carpén; Anu Kantele; Olli Vapalahti; Marjaana Tiainen; Pentti J. Tienari; Kai Kaila; Johanna Hästbacka; Liisa Myllykangas
• Keywords: Adult; Male; 0301 basic medicine; APOE4; Heterozygote; Post-viral fatigue; Apolipoprotein E4; COVID-19 sequelae; Cohort Studies; 03 medical and health sciences; Risk Factors; Humans; Prospective Studies; RC346-429; Neuropathology; Finland; Genetic Association Studies; Aged; Biological Specimen Banks; Cerebral Hemorrhage; SARS-CoV-2; Research; Patient Acuity; COVID-19; Middle Aged; Mental Fatigue; Brain microhaemorrhage; Microvessels; Female; Neurology. Diseases of the nervous system; Autopsy

AbstractApolipoprotein 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.