Mary Wilson
Well-known member
Published: 20 November 2022
DOI https://doi.org/10.1038/s41392-022-01241-2
Yuxin Hou, Chang Li, Chaemin Yoon, On Wah Leung, Sikun You, Xiaoming Cui, Jasper Fuk-Woo Chan, Duanqing Pei, Hoi Hung Cheung & Hin Chu
Coronavirus Disease 2019 (COVID-19) is associated with a variety of neurological complications, including encephalopathy, encephalitis, dementia, and others.[SUP]1[/SUP] The pathogenic mechanism of these neurological manifestations remains incompletely understood but may be due to factors such as coagulation problem, immune-mediated response, or direct viral invasion into the central nervous system (CNS).[SUP]2[/SUP] We and others previously reported that ancestral SARS-CoV-2 could infect and replicate in human brain organoids.[SUP]3,4[/SUP]More recently, SARS-CoV-2 Omicron BA.1 emerged in late 2021 and demonstrated altered virological features including increased immunoevasion and attenuated pathogenicity comparing to SARS-CoV-2 wildtype (WT) and previous variants.[SUP]5[/SUP] However, the neuroinvasiveness of Omicron sublineages remain unexplored. Here, we investigated the neuroinvasion and neurotoxicity of Omicron BA.1 and BA.2, and compared the findings with those of SARS-CoV-2 WT and Delta in human forebrain and midbrain organoids. Our results demonstrated that BA.2 replicated more efficiently while triggered lower levels of type I interferon response than that of SARS-CoV-2 WT, Delta, and BA.1 in both human forebrain and midbrain organoids. In addition, BA.2 triggered substantially higher levels of apoptosis in the infected human forebrain and midbrain organoids. Together, these findings suggest that BA.2 may be different from SARS-CoV-2 WT and previous variants in its capacity in targeting and causing diseases in the human brain.
To model the susceptibility of human brain cells to different SARS-CoV-2 variants, we established forebrain and midbrain organoids from human embryonic stem cells following previously described protocols (Fig. 1a, b).[SUP]6,7[/SUP] Forebrain organoids mimic human cerebral cortex development and contain dorsal telencephalic tissue after 3 weeks of differentiation. ...
https://www.nature.com/articles/s41392-022-01241-2
DOI https://doi.org/10.1038/s41392-022-01241-2
Yuxin Hou, Chang Li, Chaemin Yoon, On Wah Leung, Sikun You, Xiaoming Cui, Jasper Fuk-Woo Chan, Duanqing Pei, Hoi Hung Cheung & Hin Chu
Coronavirus Disease 2019 (COVID-19) is associated with a variety of neurological complications, including encephalopathy, encephalitis, dementia, and others.[SUP]1[/SUP] The pathogenic mechanism of these neurological manifestations remains incompletely understood but may be due to factors such as coagulation problem, immune-mediated response, or direct viral invasion into the central nervous system (CNS).[SUP]2[/SUP] We and others previously reported that ancestral SARS-CoV-2 could infect and replicate in human brain organoids.[SUP]3,4[/SUP]More recently, SARS-CoV-2 Omicron BA.1 emerged in late 2021 and demonstrated altered virological features including increased immunoevasion and attenuated pathogenicity comparing to SARS-CoV-2 wildtype (WT) and previous variants.[SUP]5[/SUP] However, the neuroinvasiveness of Omicron sublineages remain unexplored. Here, we investigated the neuroinvasion and neurotoxicity of Omicron BA.1 and BA.2, and compared the findings with those of SARS-CoV-2 WT and Delta in human forebrain and midbrain organoids. Our results demonstrated that BA.2 replicated more efficiently while triggered lower levels of type I interferon response than that of SARS-CoV-2 WT, Delta, and BA.1 in both human forebrain and midbrain organoids. In addition, BA.2 triggered substantially higher levels of apoptosis in the infected human forebrain and midbrain organoids. Together, these findings suggest that BA.2 may be different from SARS-CoV-2 WT and previous variants in its capacity in targeting and causing diseases in the human brain.
To model the susceptibility of human brain cells to different SARS-CoV-2 variants, we established forebrain and midbrain organoids from human embryonic stem cells following previously described protocols (Fig. 1a, b).[SUP]6,7[/SUP] Forebrain organoids mimic human cerebral cortex development and contain dorsal telencephalic tissue after 3 weeks of differentiation. ...
https://www.nature.com/articles/s41392-022-01241-2
