J Exp Med
2021 Mar 1;218(3):e20202135. doi: 10.1084/jem.20202135.
Neuroinvasion of SARS-CoV-2 in human and mouse brain
Abstract
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.
© 2021 Song et al.
NO PRIONS in this paper. But SARS-CoV-2 gets into human brain. “ Upon histological examination, we found multiple microscopic ischemic infarcts in the subcortical white matter, ranging from acute to subacute, and with focal hemorrhagic conversion (Fig. 8 C and Fig. S5 A). These varying stages of infarction indicated a temporal sequence of continued ischemic events. Most infarcts showed signs of tissue damage and localized cell death, and positive viral staining was present predominantly around the edges of the infarct and to a lesser degree within the center. At the hyperacute stage of infarction, viral proteins were present in endothelium. These infarcts are present predominantly in subcortical white matter, not within the cortex. In other samples, we found suspected viral staining in locally ischemic regions (Fig. 8 D and Fig. S5, B and C). Remarkably, all the regions of positive viral staining showed no lymphocyte or leukocyte infiltration. This is in contrast to other neurotropic viruses (ZIKV, rabies virus, and herpes virus) in which the infection is typically accompanied by large number of immune cell infiltrates, including T cells. These findings suggest that, although SARS-CoV-2 has neurotropic properties and can infect neurons in patients, it did not invoke an immune response typical of other neurotropic virus in this particular case.”
Elon discussing MRNA
On turning people into a butterflies
Discussing messenger RNA, the molecules triggered by Pfizer and Moderna’s Covid-19 vaccines, Musk said we should appreciate that the current medical advances using them amount to “the digitisation of medicine”.
“You can literally create an RNA or DNA sequence like a computer programme and then encapsulate that – you have to multiply it billions of times – in a liquid shell, so it looks like a tasty treat for yourselves, and you can literally do anything,” he said.
“This is actually the future of medicine,” he said. “You could probably figure out how to turn someone into a literal butterfly. Your cells are biological computers. Just like an old-school computer where you feed it a tape or a punchcard. You feed your cells which are tiny biological computers this punchcard and they will do whatever that punch-card says.
“So that was probably the big eye-opener of 2020 – just understanding the potential of RNA.”