New preprint from the lab. We’ve joined the fight, and looked at tropism of the virus causing #COVID19 in the brain. Great collaboration with @AnnaAlbecka and Leo James group. Here’s a breakdown of what we find. 🧵
biorxiv.org/content/10.110…
biorxiv.org/content/10.110…
We first look at expression of the viral receptors in human brain organoids and find not much expression, at least at the RNA level, in neural cells. BUT interestingly we find a lot of expression in the choroid plexus. So... what’s the choroid plexus you say?
The choroid plexus (ChP) is what makes your cerebrospinal fluid! It’s also a really important barrier that prevents things from entering the CSF from the blood. So it’s like a gatekeeper, protecting the brain from viruses, toxic compounds and immune cells and factors.
Next, we tested different ways of looking at whether SARS-CoV-2, the virus causing COVID-19, could enter brain cells, and we found no entry into neural cells but abundant infection of ChP.
We thought that’s odd, others have reported it infecting neurons. But then we realised we were using a lot less virus so then we put on 10X more virus, and we could finally see (a couple) neurons infected. So basically, not a very effective virus at infecting neurons.
Important side note: I should also stress these were telencephalic organoids, so neurons here are cortical excitatory and inhibitory neurons (based on previous extensive characterisation of these organoids).
But back to the ChP, we noticed that after several days of infection of ChP tissues, when we tried to collect them for analysis, a lot of them just fell apart! So we looked at whether the contacts between cells were still intact, and found really disrupted contacts.
All in all, our data suggests that this virus could infect this important 🧠 barrier, and if that’s infected then it can become leaky to lots of bad stuff getting in to the brain.
This could be particularly relevant to chronic fatigue syndrome (CFS/ME) where there is evidence of abnormal inflammatory molecules getting into the brain. And CFS/ME symptoms seem to be a key aspect of the increasing reports of #LongCovid.
Much work still needed, but hopefully this small contribution might provide at least some insight into the neurological aspects of this horrible disease. And open up ways of preventing or reversing them!
In all my effort to describe the work and make sure to tag our collaborators, I forgot the tag the most important person, Laura Pellegrini @laupellegrini who led this work!!
