Ep 136 Long Covid: A long time coming

couldn't work a full day. I had terrible fatigue, dizziness, nausea trouble, sleeping, headaches, brain fog, and cognitive difficulties, and for some reason I was really light sensitive and had sore eyes. The cognitive difficulties were definitely the worst. I could only work a couple hours before it felt like my brain would just shut down, and once I couldn't figure out how to send an email after I'd written it and just deleted it instead. I also couldn't do

all of my work tasks. Some of my work involved writing code, and I couldn't do that, So I really could only do this more simple parts of my job, and only for a couple hours a day. If I felt a little better one day and worked longer, the next day would be much much worse. It was a temporary job, so I struggled through the last two months working modified hours, and afterwards I had a month off

between contracts, during which I slowly improved. I went back to work full time in May of twenty twenty two. I was still experiencing fatigue, headaches, and some brain fog, but I could work, and I continued to improve over the summer, and by August or September I felt like I was nearly back to normal. At that point, I still got headaches when I overdid it physically, and I was slightly more tired than normal and still had to rest a little bit more, but mostly I could live

life as usual. I was socializing, exercising, working, and I thought I was essentially back to full health. But in November of twenty twenty two, my long COVID symptoms came back. I will probably never know what caused the relapse. I had moved house and moved offices and experienced distressful event all in October, but I might have gotten COVID a

second time. I never tested positive, but rapid tests weren't particularly accurate for the variant that was circulating at the time, and I didn't have access to a PCR test this time. The physical symptoms were much worse than what I'd experienced before. On top of all the other things that I had in the months after my infection, I also experienced muscle pain. When I would walk for ten minutes or go up the stairs, it would feel as if I had done

thousands and thousands of squats the day before. I also experienced unexplained muscle weakness. Sometimes I couldn't get myself out of the bath and my partner would have to lift me out, and he also had to help me up the stairs. I also experienced anxiety of a type I'd never had before, and other weird symptoms. For instance, my taste and sense of smell were affected for the first time.

The brain fog and cognitive stuff wasn't quite as bad as the first round, so I was able to keep working, although really not do much else for most of the winter. But again I slowly improved. I started to be able to walk further, cook dinner on top of working, and I thought I was back on the path to recovery again by the time spring rolled around. In April twenty twenty three, I had a surgery that I'd been putting

off for about a year because of long COVID. I healed from the surgery well, but for some reason, when I returned to work at the end of May, going back triggered another, much, much worse relapse. It was as if my central nervous system had collapsed. I couldn't walk properly and had a weird, stilted gait that I couldn't control. I was extremely dizzy and my sense of balance was heavily affected. I would fall against door frames and things like that, and my partner even took me to emergency

to make sure that I wasn't having a stroke. I haven't been able to return to work since. For the summer of twenty twenty three, I was bedbound for the first two and a half weeks and couldn't do nearly anything for myself, and I was housebound for the rest of the summer. I had extreme fatigue, extreme dizziness. The nausea that I'd experienced before progressed to vomiting. I had other stomach symptoms. I had weird visual disturbances as if my focus was lagging and an elevated heart rate, my

activities were severely restricted. I couldn't drive, I couldn't tolerate reading for most of the summer, or looking at screens at all, which meant no TV as well as no computer work. Everything was exhausting. Brushing my teeth was exhausting, Bathing was exhausting. Even eating was exhausting, and I needed

to take multiple even just brushing my teeth. I was unable to tolerate standing or even sitting upright, so I spent most of the summer lying flat or reclined, listening to audiobooks, and generally being bored out of my skull on top of everything else, in August I was diagnosed with posteral orthostatic tachycardia syndrome or POTS, which helped explain some of the dizziness, the inability to remain upright, and

of course, the elevated heart rate. The most difficult things in all of this have been not knowing how much or even if my condition will improve. Pacing is also unbelievably difficult. Figuring out what level of activity is okay is really hard because there's a delay in consequences. If I do something one day, I won't know what effect it will have on my symptoms until the next day

or a couple days later. The other difficult thing about pacing is not overdoing it on days when you feel a little bit better, because in my experience, that almost inevitably leads to a crash. The boredom and isolation are also really difficult for most of the summer, seeing a friend for even an hour or so would completely exhaust me and make all my symptoms worse. And there's also

the loss of independence. I was a very independent person before all of this, and becoming reliant on another person for pretty much everything, from making my meals to driving me to appointments was a really difficult adjustment to me. And there are also small things. It seems kind of silly, but not being able to condition my hair because it would be too much on top of washing it was so so frustrating and still is. There are things that

are helping. I'm on a beta blocker now, which was prescribed for the POTS, which helps control my heart rate and has also allowed me to slowly become adjusted to being upright more often. I was also prescribed low dose naltrexone, which has helped me slowly increase what activities I can do. During the summer, any increase in activities resulted in a crash, and I really made no forward progress at all. So the low dose meltrekzone has really been a game changer,

even if progress is still slow. I also saw a neurological optometrist, so I got a new glasses prescription that's already helping much much more than I ever thought it could. It's easier to read, and I can already tolerate screens a little better. I have far far fewer headaches, my eyes are less sore, and I'm also much less light sensitive. It's also helped a little with dizziness and nausea, and

I'm really looking forward to starting vision therapy soon. So now it's just over two years into the roller coaster that has been my long COVID experience, and where I am now is of course, I've been tested for a million different things just to eliminate other potential causes of my symptoms, and although I'm still reliant on my partner for driving and nearly all of the household tasks, I'm actually feeling pretty hopeful My quality of life has improved

due to the medication, and I think also to aggressive pacing. I'm still resting the vast majority of the day and pacing every single activity, whether it's social or mental effort, or physical or even emotional. But I can now see friends a lot more easily, which has made a huge difference. And most importantly, I'm continuing to make forward progress, which I think has been the most important for my mental health.

Even if it is really slow, I know that I'll very likely always have to live within limits, So for now, I'm just trying to focus on small milestones like being able to sit up a little longer, make myself breakfast, and going for walks in our yard, which are great because I can measure my progress based on how much further I can go without causing a crash.

over the course of just a few years. And we're gonna kind of follow this up next week with an episode on myalgic and cephalomyelitis slash chronic fatigue syndrome because there are, as you'll learn, a lot of parallels, a lot of similarities between these two conditions, and I think that and we're going to delve into different aspects in each of them. But long story short, as if we've ever made a long story.

called Anatomy of a Pandemic, covering everything that we could about COVID. But never in any of those twenty one episodes did we talk about.

But anyway, getting more into that, Yeah, Also, I think that like revisiting those episodes is a really interesting opportunity to remind ourselves of how much we didn't know. Like there are so many things that are just innate knowledge about COVID now.

well as on all of our social media channels. And what else do we say here?

impacted this or that town. But rarely are the people with the disease portrayed as being central to the narrative, despite the fact that without them there would be no narrative, and they're mostly described passively rather than actively, as people

that a disease is happening too. As though they have no agency over their own story, and this telling and one that I am definitely guilty of on the podcast, it can do a huge disservice to the people living with or dying from a disease, or even just in the widespread recognition that people not directly involved in biomedicine can make a huge impact like they can and long

COVID is kind of a great example of this. And sometimes these narratives do include the contributions of people outside the realms of healthcare or research, such as with HIV AIDS, activists demanding better research, better access, and better care, or people with chronic pain collectively saying stop the medical gaslighting.

But often as time goes on and as histories are more filled in, those patient or activist contributions are often overwritten as we learn more about, you say, the path of physiology of a disease, or as a diagnostic tool or treatment is developed, and then that's what becomes the central narrative. Yeah, that's so true, It's right. I was like, WHOA all the time. How many patient stories, patient centered stories have I just glossed over in every single episode

of this podcast? Probably a lot? And I really hope that this doesn't happen with long COVID, because I think that long COVID is one of the most incredible examples of people coming together to advocate for themselves for better care, to change the way we recognized or characterize a disease, to raise awareness about a condition that was and sometimes is very much maybe even often is still dismissed because of its fuzzy edges it's hard to define qualities, and

its laundry list of symptoms, and its lack of a

clear diagnostic test. There are so many lessons that we should learn about long COVID, like how much we still don't know about viral infections and our immune response to them, How our measurements of disease are inadequate a lot of the time, splitting it into does it kill you or not, like that's not necessarily a very helpful metric, the power of patient activism, and how the medical system fails people who don't fall into tidy disease categories or respond to

disease in any way outside of what is expected. How are political There's more, how our political and medical infrastructure does not provide adequate support for people with poorly understood chronic diseases, how popular media representation of science as full of certainty creates unrealistic expectations and erodes public trust. Obviously, there's a lot that we could cover.

ways that science and medicine handles uncertainty. And I'm hoping that at the end it'll be kind of like a good lead in at least to like next week's episode on my algic and cephalomyelitis as sort of like a compare contrast, what are we still not doing enough in these different diseases?

Pandora's box had been opened. Like whatever metaphor you want to use for the house gates that would eventually become COVID nineteen. I feel like it's hard to remember now after years of reading about or hearing about COVID, but at that point in time, in early twenty twenty, we were still dealing with an incredible amount of uncertainty about what this disease was. Like, I mean, we didn't even have like our name for it. Changed By early twenty twenty,

we knew that it could be deadly. We knew that it could cause severe disease. We knew it was a respiratory infection, but we also knew that for most people it seemed to cause mild infection, and that full recovery would happen within a matter of a couple of weeks or maybe three to six weeks for someone who had a severe case of the disease. That was the line, that was the narrative. We heard it over and over and over again. And that was the case for many people,

but for others absolutely not at all. And by March and April twenty twenty, people began sharing on social media there are symptoms that lingered long after they quote unquote should have recovered, and some news outlets published stories about support groups founded by patients, as well as first hand accounts of the long road to recovery that some people faced when it came to this disease, and some of these stories gained quite a bit of attention, like that

of infectious disease professor Paul Garner, who described weeks of suffering through a quote roller coaster of ill health, extreme emotions, and utter exhaustion end quote, which he named the COVID

long taiale. And one of our faves, Ed Young, published an article called COVID nineteen can last for several months, which featured the stories of several people who were experiencing lingering and incapacitating illness, often cyclical, long after recovery was quote unquote supposed to happen as well as and This article also mentioned support groups that helped people navigate this

illness or at least provide empathy and understanding. This article is where the term long haulers first appears the now more commonly used term long COVID. I think it's maybe that's like equal, but I think long COVID is like the medical entry.

you want to hear the first hashtag long COVID tweet? Yes? I do, okay quote the hashtag long COVID. Hashtag COVID nineteen is starting to be addressed on major newspapers in Italy. Two. An estimated twenty percent of tested patients remain COVID positive for at least forty days. Professor from tor Gatta University of Rome notes, there is a lot we don't know about this virus.

I was like, yeah, it's there. But also I think it's it's really interesting in the context of this because it kind of talks about long COVID or like it references long COVID as though it already is a hashtager already as a concept that's widely known, and so by may there is sort of this at least awareness in some circles that this is a thing that is actually happening.

or the just these pieces were about, like the emergence of this term on social media and the role of social media in connecting people who were experiencing symptoms, you know, long after what was expected. But as the weeks went on, you can actually witness the term long COVID gain legitimacy

in these news articles. You know, it started to appear without the quotes around it, and the articles were asking questions more along the lines of what could be causing this long COVID rather than could COVID cause these long

term effects? And the language in these articles no longer really hedged about whether or not someone's symptoms following infection from COVID were linked to the infection or if something else was going on, it was simply taken as fact that some people did not recover from COVID on the expected timeline, and that this long COVID could be debilitating with significant effects to mental health, physical health, their personal life,

and many other aspects of life. This was a huge development, honestly to see this happen within a matter of months, and it was made by the endless work of the many patient led groups that advocated for recognition and to be part of the conversation. But recognition and acknowledgment in popular media alone wasn't enough. Like we're talking about a

medical condition that can severely impact someone's life. For there to be hope of treatment for long COVID, for there to be diagnostic criteria that would enable someone to exercise their workers right and benefits, we needed to have an understanding of what was actually going on physiologically, and for that we needed medicine and biomedical research. Healthcare workers and researchers knew that some people were experiencing symptoms long after

they should have recovered. They were seeing it and in fact, since healthcare workers on the frontlines of the pandemic had some of the highest rates of infection with COVID nineteen, especially in those early months, these healthcare workers had some

of the highest rates of long COVID. And side note here, I think that this is an interesting contrast to the myologic and cephalomyelitis chronic fatigue story because, as I'll talk about, it took a lot longer to that took a lot longer to gain legitimacy as an actual condition that could affect anyone rather than just like pesky board women lingering

and wanting attention was sort of like the stereotype. And having such a high rate of healthcare workers added weight to the early argument that COVID, that long COVID was a real thing. And I think that this says a lot about biases in medicine and society more generally, and also bias in terms of like when subjective symptoms are more likely to be chalked up to personality or gender rather than taken seriously.

we'll get into that next week a lot. Yeah, But I also don't want to misrepresent long COVID as a thing that went from you know, hashtag one month to the next month being one of the first if not the first patient creed diseases and totally accepted by the medical community as well as society at large, without being challenged or anyone being disbelieved. Because that's not the case.

But these things happened and continued to happen in different ways, and I think it's important to talk about those differences because I think it can highlight the ways that science and medicine handle uncertainty, and how that uncertainty can be communicated, often at the detriment of both trust and science and

empathy and support for patients. And so this is sort of like I really struggled with how to put this together, and I hope this is coming across, so please stop me if you have questions, But like I wanted to talk about how long COVID as a concept has faced dismissal or challenges, and then also how people with long

COVID experience on an individual level challenges and dismissal. So it and I think it really kind of relates in many ways to research on one end of things, like science and research on one end of things, and then medicine and healthcare, like the approach of healthcare workers on the other side of things. That makes sense that framing, we just get it. I'll just start. So let's start first with the clinical concept of long COVID and how

science deals with uncertainty. Things take a long time with science, longer than most of us probably think. If we remember in our tonsils episode, how it took decades for research about tonsil ectomies to make its way into the clinic and then into general knowledge. That wasn't a fluke. It takes years for a scientific concept or finding to gain acceptance within a specific field, years of data collection, analysis, publication of perioview journals, replication of studies, and so on.

And this time lag is not because there isn't urgency in science. There most definitely is, especially with topics that deal with things like health. This deliberate and rigorous approach to establishing scientific knowledge is necessary to make sure that the concepts or medications or practices that are being studied are grounded in reality that we have enough information to say this seems to be what's happening. Biomedical science could be described as cautious, but that caution is for a

very good reason. The stakes are high, and researchers need to make sure that what they uncover could be applied to human health to do good rather than harm. But I think that this time lag can be frustrating at times, like when you read a headline about a possible new revolutionary treatment for Alzheimer's disease and you think, great, maybe your uncle who was just diagnosed can get this treatment right away and within the next few months, and wouldn't

that be great? But then in the article you read that it's just preliminary results from a pilot study in mice, and that it would probably take ten plus years and continued experimental success for the drug to even go up for approval, And then at what point does it go for approval? And then would he even be able to

pay for it in the end? You know, it's like all of these different things, Or like when the world is grappling with a new and potentially deadly respiratory virus and no one seems to know whether to disinfect your groceries or male or how long someone's infectious, or what social distancing indoors versus outdoors should look like. It's frustrating when science doesn't have all of the answers because we

expect them to. And I think that those expectations for science and scientists have been created in part by how the popular media talks about science and reports on scientific findings. Nuance and uncertainty and context often disappears to make room for brevity or just a good story. In a scientific article. The authors may say this is a total made up example.

These findings suggest that lead contamination of drinking water was prevalent at times in a few regions of ancient Rome, and the corresponding news piece about it says fall of Rome finally solved lead poisoning to blame. It's like, Okay, that's catchy, I understand, but like, that's not what they're saying. Uncertainty is a necessary part of science, but it doesn't make for a catchy story, and it's hard to admit uncertainty. It's not just about the popular media framing science as

having all the answers. It also has to do with many scientists not feeling comfortable admitting what they don't know, especially if new information contradicts their existing knowledge. What does all of this has to do with long COVIDHA everything. I think that when researchers or quote unquote science as a field finally recognized that some people experienced debilitating symptoms long after the accepted two course of illness, it felt like, finally, it took you long enough to see that this was

happening to acknowledge it, which I totally understand. But at the same time, I think we need to ask how much of that that time, that time lag, or that timing was due to science being science, you know, cautious grounding observations and data, coming up with a consensus for diagnostic criteria so as tomize confusion, you know, having agreement

about terms. And how much of it was science and scientists being reluctant to acknowledge contradictory data, or just having a tendency to label people's experiences as outliers, or being unwilling to say, maybe we don't know as much about this as we thought, maybe we were wrong. Long COVID didn't fit with the narrative of COVID as a respiratory

disease where recovery, unless severe case was rapid. It's a weird paradox of science where we can look back on centuries of progress, progress made by new information being integrated into existing information, and yet we seem to have this instinct to immediately reject contradictory information without looking at it more closely, so like we can see how far we've come without imagining that we might still have further to go.

Oh yeah, I don't have the answer for how much it was science being cautious versus science being dismissive about the concept of long COVID. Regardless, this period of waiting for long COVID to be quote unquote scientifically legitimate was very much felt by people with long COVID who needed a diagnosis to exercise workers' rights or disability rights, to have an answer for what was happening, even just to learn,

even just to say what I'm experiencing is real. And while this battle for the recognition of long COVID as a concept was happening on a collective scale, people with long COVID were also fighting their own fight on a very personal one, which brings me to some of the

ways that medicine deals with uncertainty. Right off the bat, I want to make clear that I'm not saying all healthcare workers or providers are dismissive or belittling, or that they all let their biases come through in their patient interactions.

I don't even want to talk about like I don't know, maybe I will, but like I really what I want to do is approach this from the patient perspective, like what people with long COVID have experienced when trying to seek health care, and this comes from data papers as well as online forums where people share their experiences, and

there are incredible forums out there. Like, honestly, I really think that it's worth just like heading to the subreddit about long COVID and what people are posting their experience is the support that they're getting from this community sort of the answers that they're getting answered, the questions that they're getting answered, at least in part or at least just like acknowledgment. I think it's really I don't know,

it's really amazing to see. And yes, maybe there will be some like direct calling out of clinicians because frankly it warrants it sometimes. Yeah, but since the COVID pandemic began, People with lingering symptoms have faced many challenges with getting

the care and consideration they deserve medical professionals. In the earlier part of the pandemic, tests were extremely scarce and at least here in the US, and they were restricted to those who had severe disease and if you were sick, but it was like mild quote unquote mild, it was

just stay home, like stay home, isolate, get better. And so when they didn't fully recover, and then they went to a doctor to say, like, what's going on, I'm still experiencing symptoms, the doctor may have doubted that what they actually had was COVID to begin with, like, well did you ever test positive?

like get a bad night's sleep. Maybe it's just stress. We don't have any evidence for what you're experiencing, so it must not exist. One paper I read from twenty twenty two by out at All reported that seventy nine percent of people with long COVID that were surveyed described negative interactions with medical professionals, including dismissal, prolonged diagnostic journeys, and lack of treatment. I want to read you a

quote from a survey participant from that paper. Quote. Because I was sick so early, I was unable to obtain positive tests, but all of my acute symptoms were COVID like many doctors nevertheless didn't believe I had COVID By the time the antibody tests were available. It was several months after I was sick, and that test was also negative.

But I also learned these tests aren't infallible. I never had these long term symptoms before, and some doctors frame it as you always had this and never realized end quote. Isn't that like just AH have the words? Yeah? And this is that is just one story from one survey but I do think it is representative of this long established pattern of medicine not dealing with uncertainty very well.

Like scientists, physicians are tested throughout all of their training and careers expected to know the right answer, have the right answer. You're going to score poorly. You're not going to perform well on this test. You're going to be like you're attending or whatever. I don't know. The terminology is going to be like, Wow, that's better, go home and read some textbooks or whatever.

on things that we can test and measure. Yes, and so when all of the things that we can test and measure are coming back as normal, it is very hard for medicine to then be like, well, what you have is real, but I have nothing to show for it, even though that is the truth of the matter. And so then what often ends up happening is well, everything is normal, so you must be fine when that is not what is the truth, and so it's it's really it's a really tough situation.

next week. Definitely, And if a patient challenges a healthcare provider, especially when that patient has more expertise on a subject, such as someone with long COVID who's been reading through forums for months, this is like there's been actual a lot of studies, a lot of work done on this with like patient expertise, and how that can influence treatment by physicians. Sometimes healthcare workers can act, can react defensively or indignantly because it disrupts this power hierarchy where it's

like I'm the expert, how dare you question me? It's not all that, it's not always the case. Like sometimes that can lead to a collaboration between patient and physician, and that's wonderful, like that's the way it should be. But this is something that can lead to like more negative interactions, I guess, and that can lead to barriers for care. And there's a citation for that by snow

at All from twenty thirteen. I think it's really important to remember that going to the doctor is an exceptionally vulnerable experience. Oftentimes maybe you're getting undressed, maybe you just have a health concern that you want to talk through. You're putting your trust in this person to help you, and this person, you know, you assume that they have these years of training. Of course they do, and that presumably they went into medicine at least in part to

help people. And then they tell you while you're making it all up, I don't believe you. That breach of trust, especially when you're in that vulnerable position, it can be so immense. Fortunately, not all physicians are dismissive. Some do try to listen. Many do try to listen. Many do try to work with their patients to come to an answer together or at least figure out what questions to

ask next. Even then, though, even if you have a wonderful healthcare provider who listens to you, who's empathetic, who is like, let's figure this out together, it doesn't mean that there aren't still challenges that people with long COVID face beyond. Just like the physical symptoms of like the fatigue, which can destroy a person, there's burnout from going to specialist after specialist, encountering new symptoms that you're like, what

is happening now? Maybe this will help me and then you your doctor, and then they refer you to another specialist, and then they refer you and you're just like spending all of this money, all of this time, all of this hope for an answer that may not that you may never get a satisfactory answer. Yeah, and then there's like dismissal from friends or family or work, and then there's just, like I kind of said, like the exhaustion

of hope, hope that things are getting better. Like maybe one day it's a good day and you're like, Okay, this is maybe maybe I'm I'm on the other side of things, and then the next day you're not, and it's just like that cycle of that Yeah, I don't know, I'm it seems incredibly exhausting and just like draining, because it's not just a physical it's not just societal or physician dismissal. It's just like everything about it, like will there be a drug, will there be a diagnosis? And

these aspects are not unique to long COVID. They're also

present with many other poorly understood chronic diseases. But one of the things that I think is so exceptional about long COVID is the enormous support and community groups that have sprung up since the early days of the pandemic, and these groups, I think really showed just how important shared experiences, how patient narratives are so crucial in understanding the full picture of a disease, how a disruption in the hierarchy of evidence can actually move our knowledge ahead

faster than otherwise. So like when you know, people started to share their experiences on these online forums, that was actually used to kind of like fuel research much faster than it would be if it was just like people sifting through medical records or something like that. Having long COVID have a hashtag, that's amazing, Like that really helped

kind of like move things along so much faster. And I really think that we cannot forget the origins of long COVID, in those who experienced it, who gave it a name, who demanded recognition and research, and who supported

each other. And I feel like there are so many more lessons or whatever themes with the history of long COVID that I mentioned at the top already, but I just want to leave you with one more and it's one that's really I keep thinking about too, is that long COVID has really highlighted how desperately we need better metrics for morbidity. We don't currently have good baselines for

what makes someone quote unquote healthy or what recovery looks like. Yeah, and maybe that's where listening to someone and believing them is so valuable. And with that, Aaron, I'd love for you to tell me what we know about long COVID as a disease. I didn't know how to end it.

This is not a new concept. This is not unique to COVID nineteen. This is not something new in the

medical literature. Not only are there dozens of other pathogens that we know of already that cause a whole variety of like post infectious syndromes, some of which are very well recognized by the medical community, and in some cases like at least a little bit well characterized, like salmonella and reactive arthritis, for example, Like we know that reactive arthritis is a thing that can happen after salmonella infection.

It's all over our textbooks. And some that are absolutely still not recognized or very controversial in the medical community looking at you lyme disease. But to anyone who had been paying attention, for example, back in two thousand and three SARS Part one, even the fact that this particular virus stars Covy two ended up causing a significant amount of long term morbidity shouldn't have been surprising, because SARS the first did the same thing. We'll get into it.

What I know. I didn't know that either. I've learned a lot researching this episode.

fatigue syndrome, Q fever syndrome. The list goes on. But one big question that I had going into this episode, like before I started researching it was something that you touched a little bit on already, Aerin, and that is that we're the numbers that we're seeing of long COVID, like the amount of human suffering from this. Is it a result of this particular virus or is it a result of the overwhelming scale of this pandemic or is it a little bit of both?

back this up after the initial Stars pandemic. Some studies suggested that up to twenty seven percent of people who survived the initial STARS infection had lingering symptoms up to a year or.

COVID compared to influenza. How do WEN focus for this episode? Which is difficult because Aaron, there's a lot and also like do we know anything? Yes, we do. So the way that I'm going to try and focus this is I'm going to try and focus on the various hypotheses that we have so far as to what is going on in our bodies in someone who's living with long COVID, and then kind of within those different hypotheses will be able to kind of understand some of the symptoms that

are associated with it. But first, let's back all the way up to like, how do we even define long COVID? Like what is the definition? It depends who you ask, I was going.

It really is variable depending on what study you're looking at. So some studies when they're looking at long COVID versus not long COVID, they're using a very different timeframe twelve weeks or ninety days or even six months or whatever their timeframe is. But at least per the CDC, four weeks is kind of the minimum for it to be considered part of the spectrum of disease that is long covid.

But what are these symptoms again, It depends because it's almost anything and everything that can affect literally every organ in our bodies. Over two hundred symptoms have been reported to be associated with long COVID, so it's it is a very huge spectrum of disease, and it's so wide that in reality this is likely not all one thing, right, Like the bottom line is, this isn't one thing. Long

covid is an umbrella. And some of the literature has started to kind of try and parse this out a little bit, and I don't know how like universally this is accepted yet, but some of what I read was suggesting that maybe there's like four different syndromes if you classify them, like a pulmonary version of long covid, a more cardiovascular dominant long covid, a neuropsychiatric long covid, and then other which is like great everything else, active gi kidneys,

all the rest. Again, I don't know if this particular formatting will hold up with time, but it's very likely that there are multiple different syndromes happening that are now under this covid umbrella long covid umbrella, and there is overlap between all of these different things, and someday we'll probably have a little bit more separation between what's going on and what the underlying path of physiology is that

drives these So let's get into that. Let's get in right now to the hypotheses that we have as to what is driving long COVID. And to do this, I'm going to separate into what the kind of biggest hypotheses are and then some of them I'll dig really deep on because we have more evidence. Okay, So the major groups of hypotheses include viral persistence, autoimmunity, reactivation of latent viruses,

and the biggest umbrella turn is immune dysregulation. And within that kind of category of immune dysregulation is also like chronic damage induced by inflammation. Okay, Okay, So I'm going to go into each of these hypotheses and within that we'll explore some of the symptoms that are strongly associated with long COVID and what we think might be driving some of those symptoms. Cool.

for a very long time following an infection. One of the tissues that seems to have a really good potential as a reservoir of SARS covy to virus is our gastrointestinal tract, and some studies have found in people with long COVID specifically persisting circulating spike protein, which people might remember is the protein that is targeted by the majority

of our vaccines for COVID. It's one of the proteins that SARS uses to enter our cells, and so it's one that we make neutralizing antibodies to in order to prevent infection or prevent illness from infection. Now, this idea of viral persistence does not necessarily mean that people remain infectious. They might not have lie virus persisting, but this persistent viral RNA or proteins can do a couple of different things. One, they could be triggering persistent immune response and inflammation just

by the presence of those viral proteins in our bodies. Two, the persistent viral proteins themselves and especially the spike protein, may cause tissue damage itself. There is some evidence that the spike protein might cause tissue damage directly and then

lead to chronic inflammation. And finally, the persistence of this virus, especially if it is whole virus in say our GI tracked just kind of hiding dormant, it could potentially be reactivated, especially if people maybe had a lower anti body tighter to begin with. But we'll get there down the line.

is living. That's a separate topic, but the virus viral whatever. Yeah, Viral reservoirs, insay, are gut cells that then are just sort of kind of able to provide like sitting there as a reservoir for this spike protein or this RNA to be every once in a while floating around in our bodies and other tissues.

or sixth disease throw back to parvo. So these viruses have been shown to be reactivated in some people with long COVID. Now, this is also something that we see in myalgic incephalomyelitis or chronic fatigue syndrome.

even constipation or chronic diarrhea. A lot of different GI symptoms can go along with long covid, there is evidence that SARS CoV two has effects on our microbiome and likely on our virum as well, especially if it's reactivating viruses that are hanging out. But again, in that case, we don't have a lot of detail on like what are those downstream effects? Why is the only happiness some people and not others? So, but the microbiome likely maybe plays a role in all of this as well.

auto antibodies. So we produce some antibodies that target proteins not of the virus, but that happen to affect cells of our own. So it's possible that in a subset of those people who are developing these autoantibodies during the acute phase of COVID, these persist and cause some of

the symptoms of lung covid. But overall, so far there is not as much evidence for this at this point, and some epidemiological evidence at least kind of It makes sense why the idea of an autoimmune reaction is like appealing,

I guess if that is the right term. Sure, because one thing to know about long covid and post acute infectious syndromes overall, like of a lot of the post acute infectious syndromes that we know of, they often occur at significantly higher rates in people assigned female at birth, And that is also true of the vast majority of autoimmune disorders as well. We still don't know why that is, and we talked in our MS episode about this. We talked in our LUPUS episode about some hypotheses as to

why that is. We don't know if these are genetic links, are they hormonal links, We don't know.

this idea of immune dysregulation. So if we go back from long COVID and think for a little bit about an acute infection with COVID, like when you first get infected, one thing that we know for sure over the course of these last four years that we have learned is that, especially in the cases of severe disease, but even in mild cases, a lot of the damage and the symptoms

of an acute infection are driven by inflammation. They're driven by our inflammatory response to this pathogen, and inflammation is our immune system reacting to try and fight off this virus. So covid, like sepsis or like any severe overwhelming infection, can in the acute phase when you first get infected, cause an overwhelming activation of our immune system and overwhelming inflammation.

Then when we look at long covid, one of the things that we see in people with long COVID in a lot of studies is higher levels of inflammatory markers long after this acute infection is over. But it's not just like, oh, it's all inflammatory and it's just high inflammation. It's not just that it's more complicated. It's a disregulated, persistent immune response. Because what we see, and this is yes, I'm sorry, but it's getting a little nitty gritty in anology.

But what we see in studies that have looked at people with long COVID is we can see increases in some markers of inflammation. Okay, but we also can see decreases in the either function or the numbers of some of our immune cells.

tried to clear it and they couldn't. So then some of these activated T cells, like the ones that have already been kind of targeted to a specific pathogen, they just kind of backtrack a little bit and they stop producing as much inflammatory stuff, and like they stop doing their anti pathogenic functions a little bit and kind of lean into a bit more of tolerance rather than trying to eliminate a pathogen.

I swear it's not more like cytokines. So another thing that we see a lot with both an acute infection but also might be underpinning some of long covid is microvascular issues and damage to our vasculature, right right, So we know that while Star's covy two is predominantly a respiratory virus, even in the acute phase, it is affecting all of our organ systems, like pretty much all of them, and one of the organ systems that it really can cause damage to is our cardiovascular system. And we see

this in acute infection as well. People with COVID, especially with severe COVID, are at significantly higher risk of blood clots and bleeding events. And so one thing that has been shown is that damage to the endothelium, the lining of our blood vessels is happening as a part of covid infection. Is this then also happening as a part of long covid? Perhaps we think that a lot of this damage is primarily from inflammation and our immune system's

response to the virus rather than directly viral mediated. But one thing that can happen is it can lead to these little microclots, and in some cases of long covid, this has been shown to lead to long term damage to blood vessels that can affect things like oxygen delivery, which is pretty important for our blood vessels to be

able to do. And this kind of damage can put people at a higher risk for a bunch of different cardiovascular diseases like heart failure, like dysrhythmias like your heart not being able to beat in a correct rhythm, increase risk of stroke. And the damage isn't just limited to the heart. We also have vascular systems everywhere else in our body, so you can see long term damage to our kidneys, you can see damage to the blood vessels in the lungs, and in some cases inflammation causing fibrotic

changes in the lungs. And there's a lot of respiratory symptoms associated with long COVID as well. Okay, but there's one more thing that I want to talk about Erin, and that is the idea of neuroinflammation and kind of within that dysfunctional signaling in our brain stem and especially with our vagus nerve. And with this, I want to spend a little bit of time to revisit the neurologic

symptoms associated with long COVID. Because of all two hundred plus symptoms that have been associated with long COVID, respiratory symptoms are very common, especially in the weeks to like short term months following COVID respiratory symptoms. Most people show some degree of improvement over time and sometimes back to baseline, depending on what their lung function was to begin with.

But in many cases, the neurologic symptoms are not only the most prevalent just overall with long COVID, but the least likely to improve. Things like fatigue and cognitive dysfunction are often present in some studies in over eighty percent of people with long COVID, and especially in people who remain symptomatic after six months or more. So let's get into a little bit more detail on what these symptoms look like and what we think might be driving them.

The neurologic symptoms are really varied, and these are things like fatigue, memory loss. It's often called brain fog like this cognitive impairment, but it also includes things like sensory motor symptoms like dizziness or balance issues. We also can see paristigias, so like abnormal sensations in the nervous system, autonomic dysfunction which can lead to dysautonomia, which we'll get into a little bit more detail on, but also like

long term loss of taste or smell. Right, we know that a lot of people lose their sense of smell and taste with acute COVID, and some people don't get that back for months. We also can see hearing loss,

we can see vertigo. Like the list goes on and on, and what I think is important about these neurologic symptoms like even listing them off like this, it does not do justice to the experience of living with these symptoms because when we say the word fatigue, or when we read the word fatigue, it is really hard to get across what that means. If you've never experienced it because fatigue sounds like tired. The kind of fatigue that can

persist after COVID can be profound. It means that someone might not be able to get out of bed at all. They might not be able to roll over in bed, or be able to get up to feed themselves. It might mean that if they do get up and out of bed to do anything like make themselves food or wash the dishes, even if they exert themselves mentally more physically, then they will end up even worse than before they

tried to get up in the first place. And that in specific is called post exertional fatigue or post exertional malaise, where trying to exert yourself results in significant worsening of this profound fatigue. It is one of the highlights of myalgic encephalomyelitis, which we'll talk about next week, or chronic fatigue syndrome, which a significant proportion of people living with

long COVID meet criteria for me and CFS. Yeah, so this fatigue is profound and significantly interferes with people's life, like being able to do basic things for themselves or for others. It's not just a feeling of being tired. It also can significantly disrupt the sleep cycle, which means that even if people would want to sleep, their sleep cycle is completely disrupted, not getting RESTful sleep no matter

how fatigue they are. And when we say something like cognitive impairment or this idea of brain fog, this again I think, does not express how significant the impairment can be. Some studies, I think out of the UK have looked at long COVID brain fog and it can be for some people like existing at the legal driving limit intoxication wise uh huh, or the equivalent of like ten years of cognitive aging. It's significant amounts of cognitive impairment that

people can live with. And what's very interesting is that some studies that have looked at people who've recovered from COVID infection with and without a diagnosis of long COVID have found rates of cognitive impairment on like standardized objective measure tests to be significantly higher than what subjective measures are.

So like, if you ask someone, they are going to report less symptoms than what they objectively measure, which means that people might have persistent cognitive effects from COVID without even recognizing a reduction in their function. Now, how do we explain any of these symptoms?

fatigue syndrome. But in general, one thing that we know is that studies have shown generalized neuro inflammation, so like inflammation in our nervous system in general, to be associated with long COVID, and that means inflammation in a lot of different parts of our brain. We also some studies at least have maybe found like certain protein signals like clumps of proteins very similar to Alzheimer's like peptides in the brains of some people with long COVID, and so

perhaps that is part of what's driving it. Again, we don't know, and we'll get into a little bit more detail on this next week. And then there's disautonomia, which is a big part of symptoms that we see in long COVID. One of the classic syndromes of dysautonomia is called POTS. A lot of people might have heard of this.

POTS stands for postural orthostatic tachycardia syndrome, and this is a type of dysregulation of our autonomic nervous system, which is the nervous system that controls our heart rate, our blood pressure, but also our gut motility, like a whole bunch of things. We see a lot of disautonomia in

people with long COVID. We have really no idea at this point what the drivers of this are aside from the fact that we also see a lot of this neuro inflammation and our vagus nerve, which goes from our brain like and touches like every single organ in our entire body literally is definitely like involved in that, if that makes sense, okay, But the specific underlying mechanisms we

don't know. So that is what we know and a lot of what we don't know about COVID long COVID, and I will just say that that is not all of it. Like, there are other systems that are very commonly affected by long COVID, things like our reproductive system and a whole bunch of different symptoms that can happen the GI system. We kind of talked a little bit

about we don't fully understand what those drivers are. And then even quite honestly, the respiratory symptoms that are associated with long COVID shortness of breath and cough are some of the most common symptoms, and we think that it's from damage to the linings of our airways, but we still don't really understand even that.

don't really have a way to diagnose it period. So at this point it's still what we call a clinical diagnosis, right, somebody who had a known or suspected COVID infection and has persistent symptoms thereafter, and what's important is that sometimes the symptoms actually aren't persistent, in that they don't start until after someone quote unquote recovers from a COVID infection, Right, they might have a very mild respiratory illness and then

a month or weeks later develop profound fatigue for example.

lot more. We'll post them on our website, This podcast will Kill You dot com, where you can find the sources for this episode in all of our past six seasons too.