Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a severe public health problem with a high rate of morbidity and mortality. A mounting number of clinical investigations illustrate that COVID-19 patients suffer from neurologic conditions in addition to respiratory symptoms. In a recent article, Yuen and colleagues present the first experimental evidence of SARS-CoV-2 infection in the human central nervous system using induced pluripotent stem cells (iPSCs)-derived platform including human neural progenitor cells, neurospheres, and three-dimensional brain organoids
While the data obtained from Yuen and colleagues is able to present the experimental evidence supporting the fact that SARS-CoV-2 attacks the human brain, there are several future steps that can be considered to enable further testing of the hypothesis regarding brain infection by this virus. First, the observed effects involving SARS-CoV-2-induced brain infection are short-term. However, in clinical practices, neurological symptoms are often persistent in COVID-19 patients. Therefore, it is essential to closely monitor the long-term consequence of SARS-CoV-2 infection in the CNS in order to advance the knowledge of durative effects of this virus on the brain. Second, three models, which are employed for the evaluation of the infection of SARS-CoV-2 on the CNS, do not possess the complete brain structure, especially lacking the integrity of blood-brain barrier (BBB). It may be difficult to explain how this virus gains entry into the brain. Our previous publications have summarized that the virus enters the brain via three possible pathways, namely, the olfactory nerves in the nasal cavity, interaction with ACE2, and a cytokine storm-induced BBB disruption.(6) Figuring out the route by which SARS-CoV-2 attacks the human brain is beneficial for the development of specific therapeutic approach to improving neurological disturbance induced by the virus. To our knowledge, future investigations involving two aspects as we mentioned above are required for the good management of COVID-19 patients with neurological symptoms.
In summary, the data provided by Yuen and colleagues offer useful experimental evidence supporting that SARS-CoV-2 can infect the human brain using an iPSCs-derived platform including hNPCs, neurospheres, and 3D human organoids. The results that hNPCs are infected by SARS-CoV-2 are emerging, as Zika virus, which associates with neurological disorders and congenital malformation,has also been shown to target hNPCs. It implicates that therapeutic strategies targeting Zika virus may be useful for SARS-CoV-infected brain dysfunction. With respect to human brain organoids employed by Yuen and colleagues, a previous study also unambiguously proved the neurotrophic property of SARS-CoV-2 in the brain,which once again highlights the advantages of brain organoids in the evaluation of CNS infection by the virus. In any way, an iPSCs-derived platform including hNPCs, neurospheres, and brain organoids is a feasible tool for probing the neurotrophic potential of SARS-CoV-2.
Reference & source information: https://pubs.acs.org/
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