Episode 82: How does COVID-19 Affect The Brain?
In this episode, Dr Bahijja Raimi-Abraham asks the question “How does COVID19 affect the brain?” with guest Professor Alysson Renato Muotri — Professor at UC San Diego, at the Department of Pediatrics and Cellular & Molecular Medicine.
If you are interested in learning more about Professor Alysson Renato Muotri, check out the previous episode, Episode 81. This episode and the previous is sponsored by the Black Dementia Company.
Dr Bahijja: How has been managing your lab and research been during COVID-19?
Professor Muotri: It has been tough, we have had to reduce the density. Our lab is usually quite lively, full of people — and we had to change that with COVID-19. We had to pivot our research during the pandemic, changing from our usual topics, to study about the effects of the COVID-19 on the brain. We have been looking more, generally, into the effects of viruses on the brain. Unfortunately, however, due to the pauses we lost many grants and have been unable to apply/reapply for many others. Most of our non-COVID related research has been paused, which is [not great for our usual research areas], but that is just life.
Dr Bahijja: While the pandemic has been difficult, there have also been some benefits in that we have been increased communication (especially through video calling) between different scientists globally — what do you think of this?
Professor Muotri: I’m with you — there are some positive lessons, and I am hoping the wider community will implement these. I used to do these international trips where I would fly, spend 1–2 days in a place and present and then leave. Now, with the video calling, I can present to larger groups of people and it is much easier. We can definitely reach a way wider audience.
Dr Bahijja: Could you talk a bit on your research findings related to COVID-19?
Professor Muotri: So it was kind of not clear in the beginning, but it is clear now that COVID-19 has a neurological component. Our questions coming into the research were mainly — can it cross the blood brain barrier? Can it infect the neural tissue? Can it infect neurons or other cells in the brain?
With our research, what we then did was get our brain organoids (Note: to learn more about organoids, listen to our previous episode, episode 81) and we infected them with SARS CoV-2. We observed the cells and any potential damage made by the virus, and found that most cell types (with some exceptions) could be infected by the virus. It is not on the scale of other parts of the body, but many neural cell types do express the ACE-2 receptor needed for the SARS CoV-2 virus the infect the cell. What was interesting, is we saw some cells died, some had inflammatory responses — but the most dramatic thing we noticed was that there was a decrease in the number of excitatory synapses in the cortex.
This potentially, could explain some of the fatigue and some of the long term symptoms [associated with long COVID], as it could be caused by this cortical damage. This happened even only 48 hours after exposure to the virus, so it was quite quick, which was shocking. Even more interesting, was that the decrease in excitatory synapses was seen even in non-infected areas of the organoid, suggesting a bystander-like effect. This suggests perhaps this could be induced by cytokines or other proteins, causing damage areas further away from the infected area. […]
Dr Bahijja: Is there any potential solution to those issues possibly caused by COVID-19 in the brain?
Professor Muotri: Yes, one benefit, is that we could potentially find pharmaceuticals or other medications that could target this issue now that we have identified it. There is one anti-viral we identified that was able to cross the blood brain barrier and blocked the viral processes within the neuron. Ideally, these medications could be adopted within clinics to prevent any potential damage to the neurons.
Dr Bahijja: Did you feel any pressure to put out research quickly due to the pandemic?
Professor Muotri: I remember talking about this with my lab — I didn’t care if I was the first or not to put something out, but I said, once we get data we can deposit it online on BioArchive. I was very afraid of potentially reporting something that could possibly be wrong, so we wanted to take our time. I would rather we take our time to make sure it was correct.
Dr Bahijja: Did you find anything suggesting any potential long term consequences or effects related to COVID-19 through your research?
Professor Muotri: Yeah, so I think these observations related to the reduction of synapses are important. We know that this is reversible, but we do not know how long it could take to revert. We have not preformed long term experiments yet, but given that many clinics have reported very long-term effects (often dubbed long covid), it is very possible there could be. The good news, however, is that the reduction in synapses is reversible and we have identified an antiviral that can prevent some of the damages.
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