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Kurki SN, Kantonen J, Kaivola K, et al. APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study. Acta Neuropathol Commun. 2021;9(1):199doi: 10.1186/s40478-021-01302-7.
Kurki, S. N., Kantonen, J., Kaivola, K., Hokkanen, L., Mäyränpää, M. I., Puttonen, H., Martola, J., Pöyhönen, M., Kero, M., Tuimala, J., Carpén, O., Kantele, A., Vapalahti, O., Tiainen, M., Tienari, P. J., Kaila, K., Hästbacka, J., & Myllykangas, L. (2021). APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study. Acta neuropathologica communications, 9(1), 199. https://doi.org/10.1186/s40478-021-01302-7
Kurki, Samu N, et al. "APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study." Acta neuropathologica communications vol. 9,1 (2021): 199. doi: https://doi.org/10.1186/s40478-021-01302-7
Kurki SN, Kantonen J, Kaivola K, Hokkanen L, Mäyränpää MI, Puttonen H, Martola J, Pöyhönen M, Kero M, Tuimala J, Carpén O, Kantele A, Vapalahti O, Tiainen M, Tienari PJ, Kaila K, Hästbacka J, Myllykangas L. APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study. Acta Neuropathol Commun. 2021 Dec 23;9(1):199. doi: 10.1186/s40478-021-01302-7. PMID: 34949230; PMCID: PMC8696243.
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Acta Neuropathol Commun. 2021 Dec 23;9(1):199. doi: 10.1186/s40478-021-01302-7.

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

Acta neuropathologica communications

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

Affiliations

  1. Molecular and Integrative Biosciences and Neuroscience Center (HiLIFE), University of Helsinki, Helsinki, Finland.
  2. Department of Pathology, University of Helsinki, Helsinki, Finland.
  3. Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, POB 21, 00014, Helsinki, Finland.
  4. Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
  5. Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
  6. Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  7. Department of Radiology, Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  8. Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
  9. Department of Clinical Genetics, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
  10. Department of Infectious Diseases, Meilahti Infectious Diseases and Vaccine Research Center MeVac, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  11. Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  12. Department of Virology, University of Helsinki, and HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
  13. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
  14. Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  15. Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, Intensive Care Unit, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, P.O. Box 340, 00029, Helsinki, Finland. [email protected].
  16. Department of Pathology, University of Helsinki, Helsinki, Finland. [email protected].
  17. Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, POB 21, 00014, Helsinki, Finland. [email protected].

PMID: 34949230 PMCID: PMC8696243 DOI: 10.1186/s40478-021-01302-7

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.

© 2021. The Author(s).

Keywords: APOE4; Biobank; Brain microhaemorrhage; COVID-19 sequelae; Neuropathology; Post-viral fatigue; SARS-CoV-2

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