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. 2020 May 4;14(5):533–541. doi: 10.1007/s11684-020-0786-5

Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain

Zhengqian Li 1,#, Taotao Liu 1,#, Ning Yang 1, Dengyang Han 1, Xinning Mi 1, Yue Li 1, Kaixi Liu 1, Alain Vuylsteke 2, Hongbing Xiang 3,✉, Xiangyang Guo 1,✉
PMCID: PMC7197033  PMID: 32367431

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.

Keywords: coronavirus disease 2019 (COVID-19), SARS-CoV-2, neurological manifestations, neuroinvasion, brain

Acknowledgements

This work is funded by the National Natural Science Foundation of China (Nos. 81873726, 81971012, and 81901095), Peking University “Clinical Medicine plus X” Youth Project (No. PKU2020LCXQ016) and Key Clinical Projects of Peking University Third Hospital (No. BYSYZD2019027). We acknowledge all healthcare workers involved in the diagnosis and treatment of COVID-19 patients all around China. We acknowledge Edanz Group for the linguistic editing and proofreading during the preparation of this manuscript.

Compliance with ethics guidelines

Zhengqian Li, Taotao Liu, Ning Yang, Dengyang Han, Xinning Mi, Yue Li, Kaixi Liu, Alain Vuylsteke, Hongbing Xiang, and Xiangyang Guo declare no conflicts of interest. This manuscript is a review and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Footnotes

Zhengqian Li and Taotao Liu contributed equally to this article and should be considered co-first authors.

Contributor Information

Hongbing Xiang, Email: xhbtj2004@163.com.

Xiangyang Guo, Email: puthmzk@hsc.pku.edu.cn.

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