For the first time, teams such as HKT have demonstrated that the new crown directly infects the human central system

the new crown outbreak, some cases have reported neurological symptoms including headaches, loss of smell, Alzheimer's disease, confusion, epilepsy and brain lesions. In a previous study of 214 hospitalized COVID-19 patients in Wuhan, 36.4% of patients showed neurological performance, with a higher proportion of patients with severe infections, accounting for 45.5%. Similarly, a French study showed that 84.5 per cent (49/58) of hospitalized COVID-19 patients developed neurological symptoms. Notablely, a recent study in Germany showed that SARS-CoV-2 RNA can be detected in biopsies in 36.4% (8/22) of deaths of COVID-19, highlighting the possibility of viral infections in the human brain.Guoyong, a professor at Li Ka-shing School of Medicine at The University of New York, is also concerned. On August 4th Cell Research, an authoritative journal owned by nature publishing group
, published an article online from
University,
Shenzhen Institute of Advanced Technology, Jinan University and other teams entitled "SARS-CoV-In addition to Yuan Guoyong, the study's authors include Hin Chu of the Li Ka-shing School of Medicine at
University and Huang Jiandong of the
Shenzhen Institute of Advanced Technology.
, there is no direct experimental evidence that SARS-CoV-2 infects the central nervous system (CNS), the team said. Their previous research has shown that SARS-CoV-2 can infect and replicate cells from neuron sources. Consistent with this finding, they found that SARS-CoV-2 can infect and damage olfactory sensory neurons in hamsters.
it is clear that, as an entry subject of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) is widely present in the brain and is highly concentrated in areas such as the black matter, the temporal back and the back buckle back to the cortical layer. Overall, the findings suggest that the human brain may be the target area for SARS-CoV-2 infections other than the lungs, the authors say.
To explore whether SARS-CoV-2 is directly involved in the central nervous system in physiologically relevant models, the team evaluated SARS-CoV-2 infections that induce human neurogenesut cells (hNPCs), nerve balls, and brain-like organs from sources of iPSCs.
first evaluated the expression of ACE2 and key coronavirus into the associated protease in hNPCs. The data showed that ACE2, TMPRSS2, tissue protease L, and Flynn protease were easily detected in hNPCs. Next, they tested hNPCs for SARS-CoV-2 infection (the complex MOI for infection is 10) and SARS-CoV infection as a control. Collect the liquid 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; Supplementary 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 simulated infection at 72 and 120 hours, respectively, to 4.7% (P < 0.0001) and 2.5% (P < 0.0001), respectively. In addition, SARS-CoV-2 infection did not significantly increase interferon and inflammatory response compared to SARS-CoV-2 induced by sars-CoV-2 in infected hNPCs.
, the team tested the infection with SARS-CoV-2 on 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 of infection. In addition, plaque measurements showed that a large number of infectious virus particles were released from infected nerve pellets. At the same time, nerve cells infected with SARS-CoV-2 were frozen and immuno-stained to analyze viral antigens. The team found that the SARS-CoV-2 nuclear shell (N) protein was easily detected in infected nerve balls, but no positive signals were detected in nerve balls that simulated infection. In addition, electron microscopes detect a large number of virus particles in empty bubbles in a bi-membrane structure, which may be where the virus particles form. These results show that nerve trots allow SARS-CoV-2 infection and support the replication of productive viruses. To see if SARS-CoV-2 can infect brain organs, the team tested 35-day-old brain organs from human source iPSC for SARS-CoV-2 infection. They found that a large number of SARS-CoV-2 antigens were detected in 72-hour infection samples, indicating that SARS-CoV-2 directly infected brain organs.
immunofluorescence staining and refocus microscopes showed that SARS-CoV-2-N signals were seen in areas around brain organs and deeper areas. In addition, cell fusion is easily seen in areas highly infected with SARS-CoV-2. No SARS-CoV-2-N signals were detected in brain organs that simulate infection.
, the team analyzed samples from infected brain organs to assess the release of SARS-CoV-2 virus particles. The results showed that the number of copies of the SARS-CoV-2 RdRp gene increased with the time of infection, suggesting that the subgenerated virus particles were released from infected brain organs. Specifically, approximately 3.2×106 copies of the SARS-CoV-2 RdRp gene were detected at 72 hours of infection, 9 times higher than at 0 hours of infection (P < 0.0001). The team then analyzed spot-clearing samples of brain organs infected with SARS-CoV-2 and found that the titularity of the infected virus peaked at 24 hours of infection and continued to be detected at 48 and 72 hours. The team noted that these results clearly show that SARS-CoV-2 can effectively infect brain organs and release viral particles. It is worth noting that dual immuno-staining shows that SARS-CoV-2-N is co-located with neuron marker TUJ1 and neurogenic marker NESTIN, indicating that SARS-CoV-2 can directly infect cortical neurons and neurogenic cells in brain organs.
, the team concluded, the results of this study suggest that hNPCs from iPSC sources can be infected with SARS-CoV-2, not SARS-CoV. A large number of viral protein expression and infectious virus particles have been detected in nerve pellets and brain organs infected with SARS-CoV-2, suggesting that SARS-CoV-2 can effectively infect the human brain. Importantly, studies have shown that SARS-CoV-2 can directly target cortical neurons and NPCs. The team noted that SARS-CoV-2 is effective in infecting human brain organs, a finding that highlights the possibility that the virus may be directly involved in neurological symptoms in patients with COVID-19.
believe these results 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, Greene-Barre syndrome, and Miller-Fisher syndrome.
stressed that the chronic or long-term consequences of SARS-CoV-2 infection in the central nervous system should be closely monitored.