{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:55Z","timestamp":1786978195201,"version":"build-2736575974"},"reference-count":80,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871014"],"award-info":[{"award-number":["81871014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The outbreak of coronavirus disease 2019 (COVID\u201019), caused by severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS\u2010CoV\u20102 and shed light on the neurological mechanism underlying the lethality of SARS\u2010CoV\u20102 infection. Among the published data, only 1.28% COVID\u201019 patients who underwent cerebrospinal fluid (CSF) tests were positive for\u00a0SARS\u2010CoV\u20102 in CSF. However, this does not mean the absence of CNS infection in most COVID\u201019 patients\u00a0because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS\u2010CoV\u20102. Among 20 neuropathological studies reported so far, SARS\u2010CoV\u20102 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID\u201019 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS\u2010CoV\u20102. In infected animals, SARS\u2010CoV\u20102 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID\u201019 patients. Several lines of evidence indicate that SARS\u2010CoV\u20102 used the hematopoietic route to enter the CNS. But more evidence supports the trans\u2010neuronal hypothesis. SARS\u2010CoV\u20102 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID\u201019 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.<\/jats:p>","DOI":"10.1002\/jmv.26570","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T13:50:23Z","timestamp":1601560223000},"page":"1304-1313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS\u2010CoV\u20102 infection"],"prefix":"10.1002","volume":"93","author":[{"given":"Jia\u2010Mei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai\u2010Hong","family":"Tan","sequence":"additional","affiliation":[{"name":"Laboratory Teaching Center of Basic Medicine Norman Bethune Health Science Center of Jilin University  Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Le","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-9829","authenticated-orcid":false,"given":"Yan\u2010Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine Jilin University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2020.104016"},{"key":"e_1_2_7_3_1","first-page":"2781","article-title":"Differences and similarities between Severe Acute Respiratory Syndrome (SARS)\u2010CoronaVirus (CoV) and SARS\u2010CoV\u20102. 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