Neuroinvasion of SARS-CoV-2 in human and mouse brain
Нейроинвазия SARS-CoV-2 в головной мозг человека и мыши
2020-06-26
SCID: 54.1/sujh8xpr
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ACE2 receptorSARS-CoV-2 neuroinvasioncortical neuron infectionhuman brain organoidstype I interferon response
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Abstract (AI)
Summary 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 whether the virus can infect the brain, or what the consequences of CNS infection are. 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 the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.
Key Findings
1
In mice overexpressing human ACE2, SARS-CoV-2 neuroinvasion is associated with mortality, whereas respiratory infection alone is not.
2
Neuronal infection in brain organoids is prevented by ACE2-blocking antibodies or cerebrospinal fluid from a COVID-19 patient.
3
SARS-CoV-2 infects human brain organoids, causing metabolic changes in infected and neighboring neurons without detectable type I interferon responses.
4
SARS-CoV-2 is detected in cortical neurons from patients who died of COVID-19, with pathological changes and minimal immune-cell infiltration.
5
The findings provide evidence that SARS-CoV-2 can directly invade the brain and infect neurons, producing consequences distinct from respiratory disease.
Research Object
SARS-CoV-2 infection and neuroinvasion in human and mouse brains
Research Subject
The capacity and consequences of direct neuronal infection, including metabolic changes, interferon responses, pathology, and mortality associated with SARS-CoV-2 neuroinvasion
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2020-06-26
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