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Since !-- the new crown outbreak, some cases have reported neurological symptoms including headache, loss of sense of smell, Alzheimer's disease, confusion of consciousness, epilepsy, and cerebral lesions.
a previous study of 214 hospitalized COVID-19 patients in Wuhan, 36.4 percent had neurologic performance, a higher proportion of patients with severe infections, accounting for 45.5 percent.
same time, a French study found that 84.5% (49/58) of hospitalized COVID-19 patients developed neurological symptoms.
It is important to note that a recent study in Germany showed that SARS-CoV-2 RNA could be detected in brain biopsies in 36.4% (8/22) of deaths, highlighting the possibility of viral infection in the human brain.
, a professor at the Li Ka-shing School of Medicine at the University of Hong Kong, and others are also concerned.
August 4th, Cell Research, an authoritative journal owned by the Nature Publishing Group and head of the Chinese Academy of Sciences, published an online article from the University of Hong Kong, the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, Jinan University and other teams entitled "SARS-CoV-2 infects human neural progenitor cells and brain organoids", in addition to Yuan Guoyong, the author of which also includes Hin Chu of the University of Hong Kong's Li Ka-shing School of Advanced Technology.
, there is no direct experimental evidence that SARS-CoV-2 infects the central nervous system (CNS) in people, the team said.
their previous studies have shown that SARS-CoV-2 can infect cells from neuron sources and replicate them.
consistent with this finding, they found that SARS-CoV-2 can infect and damage the olfactory sensory neurons of hamsters.
It is clear that, as an entry recepor to SARS-CoV-2, angiotensin conversion enzyme 2 (ACE2) is widely present in the brain and is highly concentrated in black matter, intraconed and backtracked back to the cortation.
, the authors say, these findings suggest that the human brain may be the target area for SARS-CoV-2 infections other than the lungs.
To explore whether SARS-CoV-2 was directly involved in the central nervous system in physiologically relevant models, the team evaluated SARS-CoV-2 infections that induce the source of pluripotent stem cells (ipsCs) from human neurogenescytes (hNPCs), nerve balls, and brain organs.
they first assessed the expression of ACE2 and key coronaviruses entering the associated proteases in hNPCs.
data show that ACE2, TMPRSS2, tissue protease L and Flynn protease are easily detected in hNPCs.
, they conducted a SARS-CoV-2 infection test on hNPCs (with a complex MOI of 10 infections), with SARS-CoV infection as a control.
is collected 0, 24 and 48 hours after infection for virus replication assessment.
interestingly, the data show that SARS-CoV-2 can be replicated in hNPCs (Figure 1a; Supplemental Information, Figure S2), but SARS-CoV cannot.
, they quantified the cellular vitality of hNPCs infected with SARS-CoV-2.
importantly, SARS-CoV-2 infection significantly reduced the vitality of hNPCs that simulate infection at 72 hours and 120 hours, to 4.7% (P.lt; 0.0001) and 2.5% (P.lt; 0.0001), respectively.
addition, SARS-CoV-2 infection did not significantly increase interferon and inflammatory response compared to SARS-CoV-2 induced high levels of cytotoxicity in infected hNPCs.
next, the team used SARS-CoV-2 to test the infection of 3D nerve balls and collected the liquid 0, 24, 48 and 72 hours after infection for virus replication assessment.
they found that the number of copies of RNA polymerase (RdRp) dependent on SARS-CoV-2 RNA increased significantly over time.
, plaque assays showed that a large number of infectious virus particles were released from infected nerve balls.
the same time, nerve balls infected with SARS-CoV-2 are frozen and immunodeficiented to analyze viral antigens.
team found that the SARS-CoV-2 nuclear shell (N) protein was easily detected in infected nerve globulins, but no positive signals were detected in simulated infected nerve balls.
addition, the electron microscope detects a large number of virus particles in empty bubbles of the two-film structure, which may be where the virus particles form.
these results suggest that nerve balls allow SARS-CoV-2 infection and support productive viral replication.
to study whether SARS-CoV-2 can infect brain organs, the team tested SARS-CoV-2 infection on 35-day-old brain organs from human sources.
they found a large number of SARS-CoV-2 antigens detected in a 72-hour infection sample, suggesting that SARS-CoV-2 was directly infected with brain organs.
immunofluorescent staining and confocal microscopes showed that SARS-CoV-2-N signals were seen in areas around brain organs and deeper areas.
, cell fusion is easy to see in areas highly infected with SARS-CoV-2.
no SARS-CoV-2-N signal was detected in simulated infected brain organs.
, the team analyzed samples from infected brain organs to assess the release of SARS-CoV-2 virus particles.
results showed that the number of copies of the SARS-CoV-2 RdRp gene increased with the time of infection, suggesting that child virus particles were released from infected brain organs.
specifically, approximately 3.2 x 106 copies of the SARS-CoV-2 RdRp gene were detected within 72 hours of infection, 9 times higher than at the time of infection .0001.
team then performed a plaque analysis of samples of brain organs infected with SARS-CoV-2 and found that the titra of the infectious virus peaked at 24 hours of infection and was continuously detected at 48 and 72 hours.
team noted that the results clearly show that SARS-CoV-2 can effectively infect brain organs and release viral particles.
It is worth noting that the dual immunodeficients showed that SARS-CoV-2-N was co-located with the neuron marker TUJ1 and the neurogenetic marker NESTIN, indicating that SARS-CoV-2 can directly infect cortological neurons and neurogenetic cells in brain organs.
!--, the result !--s of this study suggest that hNPCs from ipsC sources can be infected by SARS-CoV-2, not SARS-CoV.
large numbers of viral protein expression and infectious virus particles have been detected in nerve balls and brain organs infected with SARS-CoV-2, suggesting that SARS-CoV-2 can effectively infect the human brain.
important, studies have shown that SARS-CoV-2 can directly target cortological neurons and NPCs.
team noted that SARS-CoV-2 can effectively infect human brain organs, a finding that highlights the possibility that the virus may be directly involved in the neurological symptoms of COVID-19 patients.
The results, they argue, provide insight into the pathological symptoms of loss of smell and taste, as well as other neurological manifestations of COVID-19, including epilepsy, encephalopathy, encephalitis, Green-Barley syndrome and Miller-Fisher syndrome.
team stressed that the chronic or long-term consequences of SARS-CoV-2 infection in the central nervous system should be closely monitored.
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