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Here we studied the genetic association between\n                    <jats:italic>APOE<\/jats:italic>\n                    and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that\n                    <jats:italic>APOE4<\/jats:italic>\n                    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\n                    <jats:italic>APOE4<\/jats:italic>\n                    carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that\n                    <jats:italic>APOE4<\/jats:italic>\n                    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\n                    <jats:italic>APOE4<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1186\/s40478-021-01302-7","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T05:19:08Z","timestamp":1640236748000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["APOE \u03b54 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-0957","authenticated-orcid":false,"given":"Samu N.","family":"Kurki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Kantonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karri","family":"Kaivola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hokkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko I.","family":"M\u00e4yr\u00e4np\u00e4\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Puttonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"FinnGen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Martola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"P\u00f6yh\u00f6nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Kero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarno","family":"Tuimala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Carp\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Kantele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Vapalahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjaana","family":"Tiainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pentti J.","family":"Tienari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"H\u00e4stbacka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-5466","authenticated-orcid":false,"given":"Liisa","family":"Myllykangas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"1302_CR1","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41582-019-0228-7","volume":"15","author":"Y Yamazaki","year":"2019","unstructured":"Yamazaki Y, Zhao N, Caulfield TR, Liu C-C, Bu G (2019) Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. 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J Allergy Clin Immunol 144:426-441.e3","journal-title":"J Allergy Clin Immunol"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01302-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-021-01302-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01302-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T05:24:34Z","timestamp":1640237074000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-021-01302-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1302"],"URL":"https:\/\/doi.org\/10.1186\/s40478-021-01302-7","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"27 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Patients and controls in FinnGen provided informed consent for biobank research, based on the Finnish Biobank Act (\n                      \n                      ). All DNA samples and data were pseudonymised. Participants of the RECOVID-study [protocol approved by Ethical board of Helsinki University Hospital (HUS\/1949\/2020)] provided written informed consent. Clinical autopsies were performed at the Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital according to Finnish legislation, with consent granted by the next of kin. The protocol covering COVID-19 autopsies was approved by the Ethics Committee of Helsinki University Hospital (HUS\/1238\/2020).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"A consent to publish individual pictures\/details was obtained from the subjects or their next-of-kin.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Pentti J. Tienari holds a patent on C9orf72 in diagnostics and treatment of ALS\/FTD and has made paid consultations to Roche, Biogen, Merck, Teva, Sanofi-Genzyme and Novartis. Other authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"199"}}