Neuroinvasion of SARS-CoV-2 in human and mouse brain
Нейроинвазия SARS-CoV-2 в головной мозг человека и мыши
2020-12-11
SCID: 54.1/k9vnvk62
Discuss with AI
ACE2 receptorSARS-CoV-2 neuroinvasioncortical neuronshuman brain organoidsneuronal infection
Figures from the paper
Abstract (AI)
Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.
Key Findings
1
Autopsy samples from patients who died of COVID-19 reveal SARS-CoV-2 in cortical neurons and infection-associated pathology with minimal immune-cell infiltration.
2
Blocking ACE2 with antibodies or administering cerebrospinal fluid from a COVID-19 patient prevents neuronal infection in brain organoids.
3
Mice overexpressing human ACE2 develop SARS-CoV-2 neuroinvasion in vivo.
4
SARS-CoV-2 infects human brain organoids, causing metabolic changes in infected and neighboring neurons without detectable type I interferon responses.
5
The findings establish SARS-CoV-2 neuroinvasive capacity and indicate direct neuronal infection as a potentially important consequence of infection.
Research Object
SARS-CoV-2 infection of the human and mouse central nervous system, including brain organoids, hACE2-expressing mice, and cortical neurons from COVID-19 autopsies
Research Subject
The neuroinvasive capacity and neuronal consequences of SARS-CoV-2 infection, including neuronal metabolic changes, type I interferon responses, pathological features, and antibody/CSF-mediated prevention of infection
Publication Details
Publication Date
2020-12-11
Journal
Publisher
ISSN
Open access PDF
Access Type
Author Information
Download PDF
Subscribe to digest
References available in scid.ai1
Cited by8
Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms2021
Pathophysiology and mechanism of long COVID: a comprehensive review2022
The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-22022
Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment2021
Interactions of SARS-CoV-2 with the Blood–Brain Barrier2021
Neurological complications and infection mechanism of SARS-CoV-22021
Animal Models for COVID-19: Hamsters, Mouse, Ferret, Mink, Tree Shrew, and Non-human Primates2021
COVID‐19 and ischemic stroke2021