🧠 Long COVID: Neurological Sequelae, Mechanisms, and Therapeutic Strategies

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The pandemic might be officially "over," but millions are still suffering. Long COVID is finally getting the scientific attention it deserves, and what researchers are discovering is alarming. In this deep-dive episode, we explore groundbreaking research from early 2025 that reveals measurable, physical changes in the brains of long COVID patients — changes that persist months after infection. We're not just talking subjective symptoms anymore; we're seeing actual damage on brain scans. From decreased brain activity to structural changes, altered brainwaves, and impaired cerebral blood flow, the evidence points to a "brain under siege." The science suggests multiple interconnected mechanisms: direct viral invasion, autoimmunity gone haywire, mast cell activation, neuroinflammation, blood-brain barrier disruption, and even gut microbiome dysregulation. Perhaps most disturbing is the emerging parallel with ME/CFS, a condition long dismissed by mainstream medicine. This isn't just another post-viral syndrome — it's potentially reshaping our understanding of how viruses impact our neurological health long-term. For the millions struggling with brain fog, fatigue, and mood disorders after COVID, this episode offers both validation and hope for future treatments. The answers aren't simple, but they're finally coming.

Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mecha

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Transcript

0:24

OK, so get this. We're going deep, deep into the neurological after effects of COVID-19, which most people now call long COVID. Right. Exactly. And you found this amazing scientific review from early 2025. Honestly, it is just like packed with insights. It really is. I think what's so powerful about this review, it was published in Frontiers in Neurology, is that it moves beyond just like listing the symptoms of long COVID. It actually digs into like measurable changes that are happening in the brain. And get this, even month after the initial infection. Yeah, that's what like the hooked me to, right? Seeing actual physical changes showing up on brain scans. But before we get too deep into all of that, let's just make sure everyone listening is really clear about what long COVID actually is. Like, what are we talking about here? So we can start with a simple definition. The CDC, they defined it as basically any symptom that sticks around for more than 28 days after you've had a COVID infection. And the ReCOVER study, which has been like tracking people and gathering all this data since 2023, has really helped us figure out which symptoms are most common, which ones have the biggest impact on people's lives. Gotcha, gotcha. So we're seeing things like fatigue, brain fog, even dizziness. These are all cropping up as like really major players in the long COVID story. Okay, so it's not just a cough that's lingering or like, you know, a little bit of congestion. It's like a whole bunch of potential problems. It can be, yeah. The review really dives deep into several specific symptom categories. It starts with fatigue and insomnia, which I mean, it's not just like feeling a little tired. This is way more intense. Right, like we're talking about serious debilitating fatigue. And the review highlights that a huge percentage of people, like somewhere around 20, 25% experience chronic insomnia along with this fatigue after having COVID. Wow. Yeah, it's a huge deal. And it's not just about feeling tired. Like you said, it impacts every aspect of their life. And it gets even more interesting, I think, when you compare COVID to the flu. Because the risk of developing insomnia for the first time ever is a whopping 92% higher after COVID compared to the flu. Whoa, that's a huge difference. I mean, I know we always say like rest is important after you're sick. But this just drives home the point that COVID is messing with our sleep in ways we're only beginning to understand. Exactly. And it really just underscores the need for ongoing research in this area. Just a few years ago, we didn't even really recognize central hypersomnia, which is a type of insomnia that causes excessive daytime sleepiness. We didn't even recognize that as a long COVID symptom. So who knows what else we'll discover as we learn more and more about this. That's true. That's true. Okay, so fatigue and insomnia are huge. But then there's also mood dysregulation. Yes. And this is where it starts to feel like a bit scarier. Yeah, it definitely can be. And I think we're not just talking about like feeling a little bit down or having a bad day. The review actually digs into some pretty alarming stats. Like, for example, people who had encephalopathy during their COVID infection. So that's like brain inflammation. Those folks were 73% more likely to later develop a mood disorder, things like anxiety, depression, or even a psychotic disorder. Wow. And it's important to remember, these are serious conditions. These are life altering. They are. And they can have a significant impact on people's lives. Yeah, that's really heavy stuff. And then of course, there's the symptom that everyone's kind of whispering about, brain fog. I feel like this term really captures the fear and confusion surrounding long COVID. It sounds almost like something out of like, you know, a sci-fi movie. It does. It sounds kind of scary. And it can be incredibly debilitating for people. And the review actually compares it to ME/CFS, sometimes called chronic fatigue syndrome, and even to chemo brain, which, you know, if you've ever gone through chemo or known someone who has, you kind of get a sense of how severe the cognitive impact can be. Yeah. Yeah. So it's not just like feeling a little bit spacey or like, you know, forgetting where you put your keys. It's actually impacting like your ability to function like day to day. Right. You're struggling to remember things. You can't focus, you know, processing even simple information becomes really, really difficult. Yeah. Yeah. And this kind of brings us to the real like heart of the review, the diagnostic tools that are helping us understand what's actually happening in the brain. Right. And this is where it moves from like subjective experiences, how people are feeling to actual objective evidence of what's going on in their brain. I like it. So, for example, PE scans. These are showing us decreased brain activity in very specific areas, particularly those involved in memory and what we call executive function. And and they're even seeing increased microglial activity, which is like a classic sign of inflammation happening in the brain. So like real physical evidence of change is happening. Yes. Not just like people imagining things. Exactly. And then we have MRI scans, which are kind of adding to this picture, you know, showing everything from white matter, hyper intensities to lesions. Wow. Even changes in the thickness of the gray matter. Wow. So these are structural changes and they could have long term consequences. So it's like COVID is leaving its fingerprints on the brain. Literally. Yeah. And then we have EEGs, which are showing us altered brainwave patterns. Oh, wow. So it's like a multi pronged attack on the brain almost. It is. It is. And then, you know, we can't forget about ultrasound, which is revealing yet another piece of the puzzle. Impaired cerebral blood flow. So we've got decreased activity, structural changes, abnormal brain waves and issues with blood flow. Yeah, it's a lot. This really paints a picture of a brain under siege. It really does. OK, so we've got all of these different diagnostic tools showing us that something is definitely, definitely going wrong. Right. But like the million dollar question is why? Like what is causing these neurological changes? And the review, it actually delves into several different hypotheses. But it seems like the answer might not be a simple one. Yeah, you're absolutely right. It's probably a combination of things. Right. So some researchers believe, for example, that the virus might be directly entering the brain, especially through the olfactory system, which is, you know, the system responsible for our sense of smell. Right. Which makes sense given that like anosmia loss of smell is so common with covid. Right. But like, is there enough evidence to say for sure that the virus is actually getting into the brain? So the evidence for that direct brain invasion is still somewhat limited, but it's definitely a possibility that we can't rule out. We know for sure that the virus can reach the olfactory bulb. Right. But how often it travels from there further into the brain is still unclear. OK, so that's like one possible pathway. Right. But what about this idea that the immune system might be like turning on itself, you know, attacking healthy brain cells? Right. That's the autoimmunity hypothesis. And it's gaining traction. And we've seen this increase in autoimmune diseases after covid-19, which suggests that, you know, maybe the virus is triggering a broader immune response that sometimes, unfortunately, goes a little haywire. So it's like the body's defense system is like overreacting. Yes. And the brain is just like caught in the crossfire. Exactly. Exactly. And this kind of seems to be a recurring theme with long covid. Yeah. The body's own responses. Right. Causing more problems. Right. Right. And another example of this is something called mast cell activation. So mast cells are part of our immune system and they release inflammatory substances when they're activated. The theory is that covid-19 might be triggering this mast cell activation, but in the brain, which then leads to widespread inflammation and a whole bunch of neurological symptoms. So it's like this like inflammatory cascade happening in the brain set off by these mast cells. Exactly. And and that kind of brings us to neuro inflammation, which seems like like a central player in many of these hypotheses. Right. Right. And remember those cytokines we talked about earlier? Yes. Well, during a severe covid infection, they can be like overproduced, right? Leading to what's called a cytokine storm. Right. Which is basically a massive wave of inflammation. Yeah. It's like the body's immune response going into like overdrive. Yeah. And the brain getting caught in the blast radius. That's a great way to put it. But the brain does have a pretty sophisticated defense system. Yeah. Right. I mean, the blood brain barrier is supposed to like keep those harmful substances out. You're right. The blood brain barrier is like a critical protective shield for the brain. Yeah. But there's evidence that covid-19 can actually disrupt this barrier, allowing inflammatory molecules and potentially even the virus itself to kind of sneak into the brain. So it's like a breach in the brain's defenses. Yeah. You can get much more vulnerable to damage. Yeah. Yeah, exactly. And this is where I like I got really surprised reading the review. You know, it suggests that the gut might actually be involved in long covid's neurological effects. Whoa, the gut. Wait, really? Yeah. This is the what we call the gut brain axis hypothesis. OK. And it's a fascinating area of research. You know, the gut and the brain, they're constantly communicating. Right. And it seems that changes in the gut microbiome, which is the community of bacteria that live in our intestines. Right. Those changes could be sending signals to the brain that actually contribute to some of these neurological symptoms we're seeing. So it's not just about the lungs and the brain, but potentially the gut as well. Yeah, exactly. It really highlights how interconnected all of our body systems are. It really does. And then to like add another layer of complexity, there's also the vascular disruption hypothesis. Right. This is the one that suggests that covid-19 can actually damage those blood vessels in the brain, leading to reduced blood flow and potentially like long term damage. Yeah. And it's fascinating because it kind of ties back to so many of the other hypotheses we've been talking about. OK. So, you know, remember that cytokine storm we were talking about? Yeah. It can damage those blood vessels. Right. Autoimmunity could be involved, you know, where the immune system is attacking the cells lining those blood vessels. Right. And even changes in the gut microbiome could potentially trigger inflammation that affects the vascular system. Wow. So it's all interconnected. Yeah. It's a very complex web with the vascular system kind of at the center. Right. Right. So we've got direct brain invasion, autoimmunity, mass cell activation, neuroinflammation, blood brain barrier disruption, gut brain access dysregulation and vascular disruption. Like it's a lot to even wrap your head around. It is. And just to add one more layer to all of this, there's also emerging research suggesting that certain gene variants might make some people more susceptible to developing long COVID. Oh, right. The genetic link. Yes. The review mentioned a gene called FOXP4, which is involved in regulating other genes and is expressed in like the lungs, gut and brain, which are like all the areas we've been talking about that are affected by long COVID. Exactly. So variations in this gene could potentially make someone more vulnerable to developing long COVID and experiencing all those neurological effects we've been discussing. So it's not just about exposure to the virus, but also about like individual susceptibility based on your genes. Yeah. And that's just another layer of complexity, but it might also offer some clues about why some people develop long COVID and others don't. Right. Right. Well, we have definitely covered a lot of ground here, but it feels like we're just like scratching the surface of what's going on with long COVID in the brain. Oh, absolutely. There's still so much we don't know. But, you know, the research is moving quickly and there's a lot of really exciting work being done. And in the next part of our deep dive, we're actually going to delve into this really intriguing connection between long COVID and ME/CFS, as well as explore what all of this means for treatment. Yeah. Stay tuned. I can't wait. Find and follow us on YouTube, Facebook, Blue Sky, Substack, and your favorite podcast provider, including Apple Podcasts and Spotify. Join like-minded curious folks broadly interested in exploring emerging pivotal science from a human perspective. Start or join a discussion about the episode's topic. Invite your friends to join the conversation, particularly if they are authors of similar papers or connect from another perspective. Back to Heliox, where evidence meets empathy. Welcome back. So last time we really got into like how long COVID can really mess with the brain. And we explored some pretty mind blowing hypotheses about like what might be causing these changes. You know, everything from like the virus directly attacking brain cells to the potential role of the gut microbiome. It's like wild stuff. It is. And you know, one of the most compelling theories that's emerged is this idea that long COVID could be messing with this very delicate balance of our vascular system. Right, right. The vascular disruption hypothesis. Yes. So essentially the idea is that like COVID-19 can damage those tiny little blood vessels in the brain. Yes. Leading to like decreased blood flow. Right. And potentially like long term consequences. Exactly. And a key part of this theory is something called endothelial dysfunction. Okay, break that down for me. What exactly is endothelial dysfunction? Well, so think of the endothelium as like the lining of your blood vessels. It's super important for regulating a lot of things like blood flow, clotting, even inflammation. So if the endothelium is damaged, it kind of throws all those processes out of whack. Exactly. And we're learning that COVID-19 can actually infect those endothelial cells directly. Oh, wow. Which then triggers, you know, inflammation and dysfunction. So it's not just affecting like the lungs or the brain. Right. But like the very infrastructure of our circulatory system. Exactly. Think about it this way. You know, your circulatory system is like the highway system of your body. Right. And COVID is causing like potholes and roadblocks. Ooh, I like that analogy. Right. It's disrupting traffic flow and that can lead to all sorts of problems. Yeah. Yeah. So this could be like a major driver of those neurological symptoms we were talking about last time, right? Like brain fog, fatigue. Absolutely. Think about it. If blood flow to certain brain regions is reduced, it could directly impact your ability to think clearly, to feel energized, even to like regulate your mood. Right. And those micro clots we talked about. Yes. And they form as a result of that damaged endothelium. Right. Leading to like even more disruption in blood flow. Yes. And potentially more damage, right? It's like this domino effect. Exactly. And what's really intriguing is that this vascular disruption hypothesis actually kind of links back to many of those other potential causes we discussed in the last episode. Oh, okay. How so? Help me connect the dots here. Okay. So remember that cytokine storm? Yeah. That can happen during a severe COVID infection? Well, that cytokine storm can actually damage the endothelium. Oh, wow. Adding to that vascular disruption. And then you have autoimmunity, you know, where the immune system might be attacking those endothelial cells. Right. And even the gut microbiome, you know, changes in those gut bacteria could potentially trigger inflammation that then spills over into the vascular system. Wow. So it's like all interconnected. It is. Let's try to solve this giant multidimensional puzzle. Exactly. And this is where that connection to ME/CFS really starts to like click because ME/CFS is also thought to involve, you know, dysfunction of the immune system, the blood vessels and energy metabolism. Right. So there are a lot of parallels there. There are. And the parallels are so strong that some researchers even believe they might be like different sides of the same coin. Hmm. Interesting. You know, maybe triggered by different viruses. Right. And maybe sharing like similar underlying mechanisms. That's a fascinating thought. It's almost like long COVID is giving us like this new lens through which to view ME/CFS, you know. Yes. A condition that's been like so misunderstood and often dismissed for way too long. Absolutely. You know, for decades, people with ME/CFS have struggled to get a diagnosis. Right. Access to proper care. Yeah. And it's often brushed aside as, you know, being psychological or, you know, all in their head. Right. Right. Like it wasn't a real illness. Exactly. But now with millions of people experiencing long COVID, the medical community is finally starting to take these post-viral syndromes seriously. Yeah. It's like long COVID has just like blown the doors wide open on this whole category of illnesses that have been like neglected for so long. I think so, too. And and, you know, if researchers can pinpoint those shared mechanisms between long COVID and ME/CFS. Right. It could lead to breakthroughs in treatment for both conditions. It's like finally some hope for people with ME/CFS. Exactly. And, you know, with all this talk about like the spike protein and its potential role in long COVID, I'm sure a lot of people listening are like wondering about the vaccines. Yes. That was my next question. Right. Could the spike protein from the vaccines be causing similar problems? Yeah. Like if it's the spike protein, that's the issue, then shouldn't the vaccines have the same effect? Right. And it's a very valid question. And so far, what the evidence suggests is that the mRNA vaccines, which, you know, only deliver the genetic code for the spike protein, they're not causing the same kind of like micro clotting issues that we're seeing with long COVID. OK, that's reassuring to hear. Yeah. But why the difference? Like help me understand that. So the current understanding is that you need the full virus expressing all of its proteins to really trigger these like unique, stubborn micro clots that resist breakdown. So it's like the spike protein might be involved, but it's not the only culprit. Right. Exactly. There are other factors at play potentially related to like how the immune system is interacting with that whole virus. OK. So it's about like the whole virus, not just a single protein. Yeah. But of course, we still have a lot to learn. It's a complex puzzle and we're still piecing together all the parts. Right. So where do we go from here? I mean, we've explored all these different hypotheses, the potential connection to ME/CFS, the challenges of finding effective treatments. What's like the next frontier in long COVID research, especially when it comes to those neurological aspects? I think one of the top priorities is developing more accurate and reliable diagnostic tools. OK. Because right now, diagnosing long COVID relies heavily on clinical symptoms. Right. Which can be so subjective. Exactly. They vary so much from person to person. Right. We need objective measures that can confirm a diagnosis, help us track how the illness is progressing. So like something concrete, something measurable to really confirm what's going on. Right. And these tools could be anything from like blood biomarkers that indicate inflammation or vascular damage. To advanced brain imaging techniques that can actually pick up on like subtle changes in brain structure and function. Oh, wow. That would be huge, wouldn't it? Like actually being able to see those physical changes in the brain. Dude. You just like validate what people are experiencing. Absolutely. And hopefully encourage doctors to take their symptoms more seriously. For sure. It would also help us monitor how well treatments are working. Oh, right. Identify those who might be at higher risk of developing long-term complications. And I imagine it'd be especially helpful in like distinguishing long COVID from other conditions that share similar symptoms. Yes. Like ME/CFS or even depression. Yeah. You're spot on. Better diagnostic tools wouldn't just like confirm a long COVID diagnosis. Right. But also rule out other possibilities which could lead to, you know, more targeted and effective treatment. Right. Right. Which kind of brings us to like another critical frontier. Developing treatments that actually address those root causes of long COVID. Not just like manage the symptoms. Right. And we've talked about, you know, some promising avenues like early anticoagulation and modafinil. Right. But those are more about like easing the symptom rather than curing the disease itself. Right. We need something that can actually like reverse the damage and get people back to like their pre-COVID selves. Exactly. And while symptom management is, of course, crucial, the ultimate goal is to find treatments that can reverse the damage that's been done and help people fully recover. It's a big goal, but I have to believe it's achievable. I think so too. I mean, we've seen incredible advances in medicine in recent years. Yeah. And I'm optimistic that like with continued research and investment, we'll find solutions for long COVID as well. I share your optimism. And I think the key here is to approach this with like an open mind and a collaborative spirit. Right. And we need experts from all different fields, neurology, immunology, cardiology, even gastroenterology, you know, to really understand this like complex web of systems. It's a true team effort. It is. And we can't forget about the patients themselves. Oh, absolutely. They are the experts in their own experience and their insights are just like invaluable to researchers and clinicians. Yeah. Their voices need to be heard. Absolutely. And their experiences should really shape the research agenda. I agree. And, you know, speaking of the patient experience, the review touched on something that I think deserves a lot more attention. Okay. And that's the psychosocial impact of long COVID. Right. Living with a chronic illness, especially one that's as like unpredictable and challenging as this one, can take a huge toll on mental health. It really can. It's not just about the physical symptoms, but the emotional and social consequences as well. Yeah, absolutely. And people with long COVID, they often face stigma, disbelief from like their friends, their family, even their health care providers. Absolutely. And they may struggle to, you know, go back to work or do the things that they used to enjoy. Right. And that can lead to feelings of isolation, frustration, anxiety, depression. Yeah, absolutely. So it's just like so crucial that we address those mental health needs alongside the physical symptoms. Yes, I agree. And so, you know, if we're going to do something that involves, you know, therapy, support groups, maybe even vocational rehabilitation to help people like navigate going back to work. Right. We need a holistic approach. Yes. That recognizes all the ways that this illness impacts people's lives. I completely agree. And this kind of brings us back to that gut brain connection we were talking about earlier. Yes. I'm so curious to hear more about that. Me too, me too. And how it might fit into potential treatment strategies. Right. And I know we like briefly mentioned it, but it just seems like an area that's like ripe for exploration. It does. It's still a relatively new area of research. Right. But there's growing evidence that the gut microbiome plays a really crucial role in our overall health. Yeah. Including brain health. Yeah. So could targeting the gut microbiome be a potential therapeutic strategy for long COVID? It's definitely worth investigating. We already have some research suggesting that certain probiotics and prebiotics, which help promote the growth of those beneficial bacteria in the gut, might have positive effects on mood, cognition, inflammation. So the idea is that we could potentially influence brain function by manipulating the gut microbiome. That's a hypothesis. It's a fascinating avenue of research and it could hold real promise for long COVID and potentially other neurological conditions. It's also like treating the brain through the gut. Precisely. And it really speaks to the interconnectedness of our body systems and the need to think outside the box when it comes to developing treatments. Yeah. That's a great point. We can't just focus on one organ or one system in isolation. We need to look at the whole person and that intricate web of interactions that impact their health and well-being. I completely agree. And that's what makes this research so challenging, but also so exciting. We're on the verge of a new era in medicine, one that recognizes the complexity of human biology and the need for personalized, holistic approaches to treatment. I love that. You know, the authors of the review, they really hit the nail on the head when they said, and I'm going to quote them here, "Ultimately, the best therapeutic course of action may be a recommendation of treatments targeting the primary suspected etiology of suspected subtypes on a case-by-case basis with adjuvant therapies targeted symptomatically." Wow, that's a mouthful. I know, right? But it really highlights this need for a truly individualized approach to treatment, right? Yes. Not everyone with long COVID is going to have the same underlying causes or respond to the same treatments in the same way. So it's like being a detective almost. Yes. It's piecing together all the clues and creating a unique treatment plan for each patient. I love that analogy. And I think that offers a lot of hope to those who are struggling with long COVID. It suggests that there isn't just one answer, but many answers. And with careful investigation, collaboration, we can find the right solutions for each person. It really does feel like we're entering this new era of personalized medicine, you know? Like moving away from that one-size-fits-all approach. Absolutely. It's about understanding the individual and their unique situation rather than just throwing a generic treatment at the problem and hoping for the best. And speaking of understanding the individual, the review actually goes into some pretty fascinating diagnostic tools that I think are worth highlighting, especially for those who are trying to make sense of their own long COVID journey. Yeah. Let's dive into that. What really caught your eye? Well, the use of PET scans, for one. They seem to be revealing a lot about what's actually happening in the brains of long COVID patients. Yeah. PET scans are amazing. They allow us to actually see the metabolic activity happening in the brain, which gives us all these clues about how different areas are functioning, or in the case of long COVID, not functioning as they should. Right. Right. And what are they showing in long COVID patients specifically? Well, they're showing some really interesting patterns, like, for example, decreased metabolic activity in certain brain regions. So for instance, the olfactory gyrus, which is involved in processing smells, often shows reduced activity in long COVID patients who have lost their sense of smell, which makes sense. Yeah, that makes sense, given how common anosmia is with COVID. Right. Exactly. But it's not just the olfactory system, right? Like, there are other areas affected, too. No, it's not. PET scans are also revealing what we call hypometabolism in areas like the amygdala, the hippocampus, the thalamus, the brainstem, even the cerebellum. Wow. So that's like a pretty widespread effect. It is. It's pretty significant. Yeah. What does this hypometabolism tell us, like, big picture? Essentially, it suggests that these brain regions just aren't firing on all cylinders. Okay. It's like they're running low on fuel, you know? Yeah. And this is due to a number of factors like reduced blood flow, inflammation, or even like neuronal damage. So it's like the brain is just not getting what it needs to function properly. Exactly. And adding to the picture, PT scans are also showing increased microglial activity in some areas, right? That's right. Microglia are the brain's immune cells, so their activation is like a classic sign that there's inflammation happening. Which just reinforces that neuroinflammation is like a key part of what's going on in long COVID. It does. And what's particularly concerning is that these changes can often be seen months after the initial infection. Oh, wow. Suggesting that the inflammation can actually linger for quite a while. So it's not just like a temporary blip, you know? Yeah. It's a potential for like long-term damage. Yeah. That's the worry. But, you know, on a more positive note, PT scans can also help us track how well treatments are working. Oh, okay. So if a treatment is effective, we'd expect to see a decrease in that inflammation and an improvement in the metabolic activity in those affected brain regions. So PT scans are not just valuable for diagnosis, but also for monitoring treatment progress. Exactly. They provide a window into the brain, helping us understand what's going wrong and hopefully how we might be able to fix it. I love that. Okay. The other tool that really caught my attention was transcranial Doppler ultrasound, or TCD. Oh, okay. I have to admit, I'd never even heard of this before. Yeah, it's not as well known as like an MRI or a CT scan, but it's a really valuable tool. So what is it? Well, it's a non-invasive technique that uses sound waves to measure blood flow velocity in the arteries of the brain. Okay, so it can tell us like how well the blood is circulating in the brain. Precisely. And in long COVID patients, TCD is showing some really interesting findings, particularly when it comes to something called cerebrovascular reactivity. Cerebrovascular reactivity. Now you're just using big words to impress me. I promise I'm not. Think of it as like the brain's ability to adjust blood flow based on its needs. So imagine you're exercising. Your brain needs more oxygen, more nutrients, right? So the blood vessels dilate to increase that blood flow. Okay, so if cerebrovascular reactivity is impaired, it means the brain's blood vessels aren't adapting properly to those changing demands. Exactly. And that can lead to a whole cascade of problems from, you know, decreased blood flow to cognitive difficulties, even headaches. And TCD studies are showing that this is actually happening in long COVID patients. Yeah, they're finding that cerebrovascular reactivity is often impaired in people with long COVID, which really supports that idea that COVID-19 can damage those delicate blood vessels in the brain, leading to long-term issues with blood flow regulation. Which again, ties back to that vascular disruption hypothesis we were talking about earlier. It does. It provides even further evidence that COVID-19 can have a lasting impact on the vascular system, even in the brain. Just fascinating, isn't it? But it's also a bit overwhelming, to be honest. You know, there's just so much we still don't know about long COVID. And it can feel like the research is moving at a snail's pace compared to like the urgency of the problem. I understand that feeling. It can be very frustrating to see so many people suffering while we search for answers and effective treatments. But it is important to remember that progress is being made. Researchers around the world are working tirelessly to unravel the mysteries of this complex illness. That's good to hear. Yeah. What are some of the most promising areas of research right now? Like where do you see things headed? Well, we've touched on a few already, like exploring the role of the gut microbiome and that potential for personalized treatments based on individual patient subtypes. And of course, there's a lot of interest in identifying biomarkers that can help us diagnose long COVID more accurately and track the progression of the disease. Yeah, reliable biomarkers would be like a game changer, wouldn't they? Both for diagnosis and for monitoring treatment response. Absolutely. And then there's the ongoing search for treatments that can actually address those underlying causes of long COVID, not just manage the symptoms. Right, right. We've talked about, you know, early anticoagulation, modafinil. But those are more about like easing symptoms rather than curing the disease itself. Exactly. We need something that can actually reverse that damage, you know, and get people back to feeling like themselves. Yes, exactly. So like, are there any promising leads on that front? There are. Some researchers are, for example, looking into antivirals. Even when given, you know, months after the initial infection, to see if they can eliminate any like lingering virus that might be contributing to long COVID. So even though like the acute phase of the infection might be over, there could still be some viral remnants like causing trouble. That's the thinking. And then there's also the approach of targeting the immune system itself. There's a lot of interest in what we call immunomodulatory therapies, which aim to basically like rebalance the immune system and reduce that chronic inflammation that seems to be driving so many long COVID symptoms. So it's about like calming down that overactive immune response. Exactly. And there are a number of different approaches being explored from monoclonal antibodies that target specific inflammatory molecules to even like stem cell therapies that aim to regenerate damaged tissues. Wow. Those are some pretty cutting edge approaches. It's incredible to think about what might be possible in the future. It is. And while we can't predict exactly what the future holds, I am optimistic that, you know, with continued research and collaboration, we will find effective treatments that can really help people with long COVID reclaim their health and their lives. I share your optimism. In the meantime, it's so important for those who are struggling to remember that they're not alone. Yes, absolutely. There are millions of people around the world experiencing long COVID. And there's like a growing community of support and advocacy out there. Absolutely. Don't be afraid to reach out for help, whether it's from, you know, friends, family, support groups or health care professionals. And never underestimate the power of knowledge. Right. The more you understand about long COVID, the better equipped you'll be to like advocate for yourself and make like informed decisions about your care. Absolutely. You know, this deep dive has hopefully provided a solid foundation of understanding, but we encourage you to like keep learning, keep exploring this topic. There are so many reputable resources available and new research is emerging all the time. This conversation has been like incredibly insightful. And I think it really underscores the fact that long COVID is this like complex and evolving challenge. It is. It's going to take time, effort and collaboration to find the answers we so desperately need. I completely agree. But I'm hopeful that, you know, by working together, sharing our knowledge, we can navigate this unstarted territory. Yeah. And create a brighter future. Absolutely. For those affected by this illness. Well said. This deep dive has been just the beginning. We've covered a lot of ground, but the conversation is far from over. It's not over yet. Stay curious, stay informed, and most importantly, stay well. Be well, everyone.