AIT Molecular Diagnostic Experts focusing on biological barriers Anna Gerhartl, Andreas Brachner and Principal Scientist Winfried Neuhaus, from the Center for Health and Bioresources, are co-authors of a new publication investigating the role of the blood-brain barrier in SARS-Cov-2 infection.
There are numerous reports linking SARS-CoV-2 infection and effects on the human neurological system in COVID-19. However, exactly how these neurological symptoms are caused remains unclear. These problems could be caused by direct SARS-CoV-2 infection of the brain, be related to but not directly caused by the immune response to the infection, or be the result of systemic infection.
The question of how the virus affects humans has been investigated by Hamburg research groups led by Priv.-Doz. Dr. Susanne Krasemann and coordinated by Dr. Ole Pless with the help of the Biological Barriers working group of the AIT Competence Unit Molecular Diagnostics.
Previous publications were able to show in animal models that both the spike protein from the SARS-CoV-2 virus and the entire SARS-CoV-2 virus cross the blood-brain barrier and could thus be found in the central nervous system (CNS). SARS-CoV-2 RNA and proteins have been detected in the brain and cerebrospinal fluid after fatal COVID-19 infection, but the viral loads have been comparatively low and the results are controversial.
For the new study, tissue samples from people who died of COVID-19 were compared with a human blood-brain barrier cell culture model. The researchers were able to identify mechanisms that were found to be consistent in both the human biopsy material and the cell culture model after infection with SARS-CoV-2. SARS-CoV-2 was also able to infect the cell culture model from the blood side and was detected on the brain side after incubation, suggesting CNS invasion. By blocking the known docking sites of the virus, the infection in the cell culture model could be significantly reduced, this model could be used for drug screening in the future.
This work was published in the journal Stem Cell Reports. The article can be found under the following link: The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2 - ScienceDirect.
Further interesting publications on this topic:
- The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells | Nature Neuroscience
- Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions - ScienceDirect
- SARS-CoV-2 crosses the blood–brain barrier accompanied with basement membrane disruption without tight junctions alteration | Signal Transduction and Targeted Therapy (nature.com)
- Biomedicines | Free Full-Text | Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing (mdpi.com)
- IJMS | Free Full-Text | Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients (mdpi.com)
- The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice | Nature Neuroscience