Reports have shown that over a third of COVID-19 cases show neurological effects. However, to date, this process is not well understood. In this report, researchers at John Hopkins University in Maryland, have shown that some neurons carry ACE2 receptors, which SARS-CoV-2, the virus that causes COVID-19, use to enter cells. Upon entry, the virus showed evidence of replication.
Professor William Bishai, co-author of the study, said: 'This study is another important step in our understanding of how infection leads to symptoms, and where we might tackle the COVID-19 disease with drug treatment.'
Organoids are tissue cultures used to replicate some of the complexity of organs. In the study published in Alternatives to Animal Experimentation (ALTEX), the researchers used induced pluripotent stem (iPS) cells to generate mini-brains they called 'BrainSpheres'. This model was developed at the University four years ago and has been applied to study other viruses such as Zika, dengue and HIV.
Organoids alone, however, cannot fully represent an organ's physiology. In this case, further research is required to understand the role of the blood-brain barrier which acts to protect the brain from pathogens. The authors speculate that the lack of neurological symptoms in some patients may reflect the action of this protective shield. 'Whether or not the virus passes this barrier has yet to be shown,' said co-author Professor Thomas Hartung. 'However, it is known that severe inflammations, such as those observed in COVID-19 patients, make the barrier disintegrate.'
Previous reports have shown that the virus can cross the placenta – the early developing fetus lacks an effective blood-brain barrier and has ACE2 receptors. This raises potential implications for developmental neurobiology. The researchers stress that this study does not show evidence of developmental disorders but urge caution during pregnancy.
'There is no doubt that the virus infects neurons and multiplies,' said Professor Hartung. 'Now we have to find out what this means for patients and public health.'