• J. Med. Virol. · Mar 2021

    Review

    Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS-CoV-2 infection.

    • Jia-Mei Liu, Bai-Hong Tan, Shuang Wu, Yue Gui, Jia-Le Suo, and Yan-Chao Li.
    • Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, China.
    • J. Med. Virol. 2021 Mar 1; 93 (3): 1304-1313.

    AbstractThe outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS-CoV-2 and shed light on the neurological mechanism underlying the lethality of SARS-CoV-2 infection. Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2. Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2. In infected animals, SARS-CoV-2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID-19 patients. Several lines of evidence indicate that SARS-CoV-2 used the hematopoietic route to enter the CNS. But more evidence supports the trans-neuronal hypothesis. SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID-19 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.© 2020 Wiley Periodicals LLC.

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