New Research Suggests Neurological Culprit For COVID Brain Fog

IRA FLATOW: This is Science Friday. I’m Ira Flatow.

KATHLEEN DAVIS: And I’m Kathleen Davis. As we’ve been discussing, COVID, unfortunately, is still very much with us. And with acute infections, is also the risk of developing long COVID. One of the debilitating symptoms is brain fog. A new study using mice cells in Petri dishes suggests that brain fog might be the result of neurons fusing together.

Joining me now to tell us more about this fascinating new research and what it may mean in better understanding brain fog is my guest Dr. Ramon Martinez-Marmol, Research Fellow at the Queensland Brain Institute at the University of / he is based in Brisbane, Australia. Dr. Martinez-Marmol, welcome back to Science Friday.

RAMON MARTINEZ-MARMOL: Thank you very much, Kathleen. It’s an honor and it’s a pleasure to be here again with you guys.

KATHLEEN DAVIS: So let’s start with the basics here. What exactly is brain fog?

RAMON MARTINEZ-MARMOL: Well, brain fog is this sensation that people that have had COVID especially may suffer in terms of they cannot think clearly, conscious sensation of tiredness, not being able to focus perfectly.

Like a little bit of a mixture between a hangover and when you cannot sleep properly in several days, like when you are a dad or a mom and you have your kid that is screaming all night, and you have to wake up several times in the night, and then the following day, you feel like, I cannot concentrate properly. That’s a feeling that could describe better this brain fog.

KATHLEEN DAVIS: And for some people with long COVID, I mean, this is lasting a long time, right?

RAMON MARTINEZ-MARMOL: Yes. That’s, unfortunately, we have had lots of feedback from patients that after experiencing COVID up to over a year ago or even more.

And after that, they couldn’t get over this strange feeling. And that happened– like sometimes that happens months after COVID. So that was very strange, and that triggered us to try to find an answer. And also, forced us to think a little bit out of the box to find other explanations different from those that are commonly used.

KATHLEEN DAVIS: Mm-hmm. So let’s talk a little bit about your research. Can you give us the big takeaway?

RAMON MARTINEZ-MARMOL: In this latest work, we found that viruses like COVID, and many other viruses, too, they use a very specific machinery to enter the cells that are going to be infected called fusogens. So that– it’s kind of the virus mix with the cell that is going to be infected.

It is well known that once the virus is inside of the cells and start all the processing of multiplication inside of the cells, the virus use the machinery from the cells to use its own biocomponent and create much more viruses. And among these components, they also create more of these fusogens.

But what we wanted to know is what happens when these viruses infect neurons in our brain. Are they going to fuse or is this something that is exclusive from the epithelial tissue? And this was very surprising for us because since over 120 years ago, the Father of Neuroscience, a Spanish scientist called Santiago Ramón y Cajal, he discovered one of the principles of neurons. They cannot fuse with other neurons.

The principles of Santa Ramón y Cajal has been proven in all the organisms, from the most simple ones until humans. So this is a basic principle. For us, we wanted to challenge that principle and see, well, maybe there– is it possible that there could be some exceptions to this basic phenomenon? And this is really what we found.

What we discovered is that once viruses like COVID infect neurons, somehow they start fusing one with the neighboring neurons.

KATHLEEN DAVIS: Mm-hmm. So why might this neuron fusion cause brain fog?

RAMON MARTINEZ-MARMOL: Well, we think that this is cause– the neuronal activity is completely affected after this fusion. Obviously, we have not been able to demonstrate that in humans. We cannot do experiments, but we use mice, we use what we call stem cells, and we derive those stem cells– human stem cells into mini-brains, and we also use life forms to demonstrate that.

And in all the different models that we studied, we found the same, which is once the neurons fuse, the activity is changed completely. So we have to understand neurons of two highly communicated cells. And this communication can be observed by electrical activity that goes from one neuron to the other and so on.

And what happened is that once the neurons fuse, instead of one fire and the other neuron responds and so on, the units that are fused fire together. And this is– we believe that this will alter the whole circuitry in the brain, and this could cause the symptoms of brain fog at the long-term, especially because once the neurons– once they are fused, they could stay fused for a very long time.

They seem fine, except that their activity was synchronized. But apart from that, the neurons were viable. They live quite a lot. We stopped the research because we wanted to show our results to the public. Now the next steps will be to check what happened to the mice and to see if we could translate better our findings to the humans.

KATHLEEN DAVIS: So because of the parameters of your study, you didn’t necessarily get to see if these neurons would heal themselves over time or something like that. Is that right?

RAMON MARTINEZ-MARMOL: Yeah, that’s right, that’s right.

KATHLEEN DAVIS: And maybe that’s something that you explore in the future?

RAMON MARTINEZ-MARMOL: Yes, yes. That’s one of the things that we want to explore. We want to do the long-term experiments with mice and with our system with the mini-brains and check how the overall circuitry is affected at the long-term. This is going to give us more information on the effects and if this brain fog really depends on this neural fusion.

KATHLEEN DAVIS: Mm-hmm. There are other studies on COVID brain fog that have linked the brain fog to inflammation or some type of immune response. Does this research support that theory?

RAMON MARTINEZ-MARMOL: We think that what’s happening is complementary. Definitely inflammation is another aspect that is going to be behind brain fog. With COVID, what’s happened at the long-term is very complex. And these are multifactorial phenomenon.

In fact, interestingly, we found that not only two neurons– or multiple neurons fuse, everything can be mixed up there. For example, when fusion happens between a known non-neuronal cell and a neuronal cell, the activity stopped completely. So this will be another cause of severe alteration in the normal function of the brain.

KATHLEEN DAVIS: Mm-hmm. So you talked about some possible next steps for the research into this. Do you think that better understanding this neuron fusion could potentially help us develop treatments for COVID brain fog in the future?

RAMON MARTINEZ-MARMOL: Yeah, yeah, definitely. You are completely right. So trying to block or try to neutralize the fusion activity of these viruses for longer could definitely be helpful for us to prevent this brain fog.

KATHLEEN DAVIS: That’s all the time that we have for now. I would like to thank my guest, Dr. Ramon Martinez-Marmol, Research Fellow at the Queensland Brain Institute at the University of Queensland based in Brisbane, Australia. Thank you so much for joining me.

RAMON MARTINEZ-MARMOL: Thank you very much, Kathleen. Thank you for this opportunity. It has been a pleasure and an honor to be here with you today.

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