Researchers at the School of Biomedical Sciences, the Department of Microbiology and the Department of Medicine, LKS Faculty of Medicine of The University of Hong Kong (HKUMed) collaborated with researchers at the Institute of Synthetic Biology of Chinese Academy of Sciences-Shenzhen Institutes of Advanced Technology to conduct a study on SARS-CoV-2 infection of human neural progenitor cells and brain organoids. The results are now published in life sciences journal Cell Research [link to the publication].

 

Background

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)¹ as resulted in over 17 million confirmed cases and more than 686,703 deaths across 218 countries and geographical regions as of 3 August 2020. This novel coronavirus primarily causes respiratory illness with clinical manifestations largely resembling those of SARS. However, neurological symptoms including headache, anosmia, ageusia, confusion, seizure and encephalopathy have also been frequently reported in COVID-19 patients. In a study of 214 hospitalised COVID-19 patients in Wuhan, Mainland China, neurologic findings were reported in 36.4% of patients, and were more commonly observed in patients with severe infections (45.5%)². Similarly, a study from France reported neurologic findings in 84.5% (49/58) of COVID-19 patients admitted to hospital³. Most Importantly, a recent study in Germany demonstrated that SARS-CoV-2 RNA could be detected in brain biopsies in 36.4% (8/22) of fatal COVID-19 cases⁴, which highlights the potential for viral infections in the human brain. To date, there has been no direct experimental evidence of SARS-CoV-2 infection in the human central nervous system (CNS).

 

Research Findings

To explore the direct involvement of SARS-CoV-2 in the CNS in physiologically relevant models, the research team assessed SARS-CoV-2 infection in induced pluripotent stem cells (iPSCs)-derived human neural progenitor cells (hNPCs), neurospheres and brain organoids. 

The results demonstrated that iPSC-derived hNPCs were permissive to SARS-CoV-2 infection, but not SARS-CoV infection. Extensive protein expression and infectious viral particles were detected in neurospheres and brain organoids infected with SARS-CoV-2, which suggest SARS-CoV-2 can productively infect the human brain. Importantly, SARS-CoV-2 infection in 3D human brain organoids was localised to TUJ1 (neuronal marker)- and NESTIN (NPC marker)-positive cells, suggesting SARS-CoV-2 could directly target cortical neurons and NPCs. 

“Overall, our study provides the first evidence of direct SARS-CoV-2 infection in human brain organoids, which contributes to our understanding on the pathogenesis of neurological complications in COVID-19,” said Professor Huang Jian-dong, L & T Charitable Foundation Professor in Biomedical Sciences, School of Biomedical Sciences, HKUMed, who led the research.

He also pointed out that the Zika virus that re-emerged in 2015 is also well recognised to target neural progenitor cells in the human brain, leading to microcephaly and severe developmental defects in the fetus and other neurological anomalies in adults. The research team suggests that the chronic or long-term consequence of SARS-CoV-2 infection on the CNS should be closely monitored.

 

About the Research Team

The research was led by Prof Huang Jian-dong, L & T Charitable Foundation Professor in Biomedical Sciences, School of Biomedical Sciences, HKUMed, in collaboration with Dr Zhang Bao-zhong at the Institute of Synthetic Biology of Chinese Academy of Sciences-Shenzhen Institutes of Advanced Technology; Prof Ivan Hung Fan-ngai, Ru Chien and Helen Lieh Professor in Health Sciences Pedagogy, Chief of Infectious Diseases Division and Clinical Professor at Department of Medicine, Assistant Dean (Admissions) of HKUMed; Dr Chu Hin, Research Assistant Professor, Department of Microbiology, HKUMed; Dr Jasper Chan Fuk-woo, Clinical Assistant Professor, Department of Microbiology, HKUMed and Prof Yuen Kwok-yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, HKUMed.

 

Acknowledgments

This work was supported by Health and Medical Research Fund (COVID190117) from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, the Shenzhen Peacock Plan Team Project, Shenzhen Science and Technology Innovation Committee Basic Science Research Grant.

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1. N. Zhu et al., A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 382, 727-733 (2020).
2. L. Mao et al., Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol 10.1001/jamaneurol.2020.1127 (2020).
3. J. Helms et al., Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med 382, 2268-2270 (2020).
4. V. G. Puelles et al., Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med 10.1056/NEJMc2011400 (2020).

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Media enquiries

Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medmedia@hku.hk).

 

Reports in newspapers/media:

1. 2020-08-04 Mirage News: HKUMed researchers first discovered SARS-CoV-2 infects human neural progenitor cells and brain organoids
2. 2020-08-04 商業電台: 港大醫學院發現新冠病毒感染人類神經祖細胞及腦類器官
3. 2020-08-04 新城電台: 港大研究首次發現新冠病毒感染人類神經祖細胞和腦類器官
4. 2020-08-04 有線新聞: 現頭痛、失語、精神錯亂等病徵 港大發現新冠病毒能感染人腦
5. 2020-08-04 Now新聞: 港大研究發現新冠病毒能感染人腦
6. 2020-08-04 星島日報: 港大醫學院證新冠病毒感染人腦 或致癲癇精神錯亂
7. 2020-08-04 蘋果日報: 【武漢肺炎】港大研究首揭病毒上腦侵神經 失味覺嗅覺兼失常
8. 2020-08-04 東方日報: 港大研究證新冠病毒可感染人腦 或致癲癇
9. 2020-08-04 TOPICK: 【新冠肺炎】港大中科院首證人腦神經可受感染 倡監察患者中樞神經慢性或長期影響
10. 2020-08-04 頭條日報: 港大醫學院證新冠病毒感染人腦 或致癲癇精神錯亂
11. 2020-08-04 晴報: 【新冠肺炎】港大證新冠病毒可染人腦 助了解神經系統併發症
12. 2020-08-04 AM730: 港大證新冠肺炎病毒可感染人類神經祖細胞和腦類器官
13. 2020-08-05 明報(印刷版): 港大研究：病毒感染人腦 現癲癇頭痛症狀
14. 2020-08-05 星島日報(印刷版): 港大醫學院證新冠病毒感染人腦
15. 2020-08-05 蘋果日報(印刷版): 港大︰武肺可上腦　致神經失常
16. 2020-08-05 東方日報(印刷版): 港大研究：新冠可侵腦部致癲癇
17. 2020-08-05 經濟日報(印刷版): 港大中科院 首證腦神經可受感染
18. 2020-08-05 成報(印刷版): 港大醫學院發現新冠病毒可感染神經細胞
19. 2020-08-05 文匯報(印刷版): 港大揭新冠「上腦」恐致癲癇
20. 2020-08-05 頭條日報(印刷版): 研究指新冠病毒感染神經細胞
21. 2020-08-05 香港仔(印刷版): 港大研究揭新冠可感染人腦
22. 2020-08-06 大公報(印刷版): 港大研究：新冠病毒可入侵腦部
23. 2020-08-08 The Street: Scientists Begin to Uncover Covid-19's Potential Toll on Brain, Nervous System