Long COVID Is More Than One Illness - The Hidden Biological Patterns Driving Chronic Symptoms with Dr. Christian Jenski | Long COVID | E165

What is happening that makes people feel like crap? Like, why are they persistently feeling tired or have brain fog or in pain? Or now all of a sudden I have autoimmunity or my muscles ache or my joints hurt, or now I have a rash or I'm itchy all the time, or my mood is horrible. I now can't sleep. Why is that happening? What are some of the proposed mechanisms?

Welcome back. Once again, we are excited to keep on going this pathway. Discussing the modern complex mystery illness phenomena in the view of the lens of Long COVID, something that we've been dealing with for, we're in our 5 years going to our 6th year now. And we talked about some of the difficulties with the traditional medical model versus comparing to the integrative model and how we're still integrating, still doing, I'm still, I'm doing new things with this Long COVID stuff. That I wasn't doing a year ago. So I continue to do new things. Like recently introduced intravenous phosphatidylcholine to use for this stuff. So we're still doing new things. At the same time, the traditional model is, is pulling away from this and saying we're closing down our research centers and yeah, you know, it's gone.

Yeah. So when the government walks away, who picks up the work, I guess is the question.

Well, typically it's the primary care doctor, internal medicine, family medicine, but in a 10-minute visit with a patient coming in where you have to screen them for depression and ask 'em about their vaccines and you know, you should have their ID and then talk to the insurance about prior authorizations. When you also talk about something complicated like this.

Yeah.

And the answer is you don't. You don't.

Yeah. And so you come— or you can't, you might try, but you're not going to get very far.

And so you need to work with someone who has the time, the talents, and also the clinical experience to kind of work through it.

Yeah. It's a lot of pattern recognition. It's a lot of understanding complex interwoven systems and systems biology approach is really what functional medicine is, functional integrative medicine. That's how we're taught and that's how we're trained and it's how we practice. It's ultimately something that almost becomes innate. I think you probably feel the same way that in the beginning, I think probably what drew you to functional medicine, one of the things was that you were already recognizing patterns as a primary care doctor, the same way that I would recognize patterns in the ER. Like that's just how our brains worked. And I think that's what the draw is for many. And probably what pushes some away, they like a more linear modality type model. But if you're looking at something as complex as long COVID and the hypothesized different mechanisms of, of pathophysiology, you have to be able to think that way in order to solve the problem. And also to triage these patients, to screen 'em, to figure out how you translate what they're saying, symptoms, subjective data, the clinical correlation into what might be happening. On a cellular level, on a macro-microscopic level. And then how do I go about potentially objectively proving that? So I maybe have a little bit of a leg to stand on and then something measurable that I can track over time besides what they're telling me. I think that's really the gift of functional medicine is that the ability to translate what someone says into something objective that I can track over time. And then the subjective kind of rebound or recourse that comes back. I think that's huge.

And we really do this in traditional medicine. We call it therapeutic trial. Someone comes in with diabetes, we're supposed to start them on metformin. You get a horrible diarrhea. Okay, we won't do that. Okay, now let's try another diabetes medication. Let's try an incretin. You try that. Oh, now you, you have upset nausea. Okay, great. Now in today's world, we're going right to GLP-1s like semaglutide, you know, but we have 5, 6, 7 different classes of diabetes medications. And sometimes people are doing glaburide and that works great for their diabetes. And sometimes it's glipside and sometimes it's metformin and We do this with hypertension. We do this with like a lot of, a lot of many diseases. We do it with ADHD, right? But the difference is in our world, we're doing that, not just, we're doing that with the person who comes in with chronic fatigue, fibro, long COVID, GI issues. So we're doing like multiple serial therapy trials at the same time that if you broke them up and did them one at a time with one specialist, you know, it would take a year or two to work through all those things we do with one patient at one visit. And that's kind of the. The enjoy I have with the complexity of it, but also it takes time.

It does. I think it's also the understanding of what intervention might be a little bit broader than others and what's gonna carry more weight, what's gonna be able to maybe cross those system lines and help that patient feel better quicker, even though it's not a race. And then can we hone in on the more specialized stuff? And I think you've alluded to it at least twice now, and we should talk about it maybe in the treatment landscape, but the membrane medicine that we're now currently doing here and how profound that can be as a one treatment. It's not one treatment, but it's the one treatment modality, right? Lipid replacement. You're going more than once, but it's affecting so much of the system as a whole because of what it does. Kind of, I look at LDN the same way, low dose naltrexone, of like the broad scope of what it does for your biology. And so I think that's really where this all kind of shines. So. Why don't we dive in a little bit into some of the proposed pathophysiologic mechanisms of action behind or underlying Long COVID? What is happening that makes people feel like crap? Like, why are they persistently feeling tired or have brain fog or in pain? Or now all of a sudden I have autoimmunity or my muscles ache or my joints hurt, or now I have a rash, or why is— or I'm itchy all the time, or my mood is horrible. I now can't sleep. Why, why is that happening? What are some of the proposed mechanisms?

I mean, let's, I think I'm gonna start with one of the ones people may have heard of, may not have heard of, but mast cell activation syndrome. Sure. And this is the idea that you have these cells called mast cells that line all the orifices in your body, GI tract, vascular bundles, all your arteries and nerve bundles. And so all of a sudden you have them in locations that can cause literally almost any symptom whatsoever. And then based on the individual, you might have chronic fatigue, fibro, brain zaps. You might have gut issues, interstitial cystitis, chronic constipation, diarrhea. I remember one of my earlier COVID patients presented with really bad diarrhea, and that was her presentation of her acute COVID actually, that we were able to avert from becoming long COVID. A quick favor. If Made for Health has given you even one idea worth trying, Hit subscribe right now. So the next one finds you automatically. And thousands of listeners already trust this show to cut through the noise. Add your voice to Apple, Spotify, or wherever you're listening. But mast cell activation syndrome is itself an amorphous thing that knowing if someone has mast cell issues gives us a whole world of therapeutic things to do. Things simple as H1, H2 blockers, Pepcid, Claritin, to more complex things like luteolin, quercetin, catatiphan, catatiphan, cromelin, all those things. And then you can get into things like letrozole, naltrexone, ivermectin, and GLP-1s also have muscle stabilization behavior. So all of a sudden now you're going from a diabetic medication and a weight loss drug into a, you know, an opioid blocker and an antiparasitic to an apple extract, right? And it's like these all have in the mast cell activation syndrome world, they all have therapeutic utilities for different symptoms. That by itself is its own world of complexity.

Yeah. That there are clinicians that just practice mast cell medicine and are just treating these patients for their mast cell disorders, which to me is usually indicative of a bigger picture. Like it's, I don't know of any patients that I have that have mast cell issues and that's it. It's usually under some umbrella. It may be their predominant clinical manifestation, but it's usually secondary to something else. I mean, mast cells need to be triggered in order to release all the badness that they house inside. So, I mean, they're just little bags of inflammatory stuff, right? They're, they're immune cells. They're white cells that ultimately, when triggered, release histamine and leukotrienes and prostaglandins and platelet activating factor and all these things that are meant to be defensive, but make you feel like crap. Especially when they're overactive, right? And like, like Dr. Hartman said, depending on where they're being triggered and where they're, they're clustered in your own biology, where they're being activated, you're gonna manifest some symptoms, whether that's neurologic or gut or skin or, or all of the above really depends on the individual. So you have to kind of pick and choose how you're gonna block the histamine. Are you gonna try to prevent mast cells from destabilizing? Are you gonna try to degrade histamine with diamine oxidase, which is an enzyme? Are you gonna go even fancier and more upstream and block the interleukins that, like interleukin-4 that causes mast cell release? And that's gonna be perilla, and that's basically an extract from a plant. You can block certain genes that create interleukin-4 with something called oxymatrin. There's, there's all these upstream, in-stream maybe, and then downstream mechanisms of, of intervention. And that's just mast cell. That's just mast cell. That's one of the proposed mechanisms behind why someone with long COVID feels like garbage. What else?

Well, let's talk about your favorite.

Yeah.

Chronic inflammatory response syndrome.

Yeah.

This is the one we both, I mean, I've vocally, like I'm never doing, it's a love-hate relationship.

It's, it's, it's, it's, it's, it's, let's not use the word favorite. It's, I'm married to it forever because it was me and I, and I know how to practice it pretty well. Man, it's hard. It's hard. And patients suffer and I can't stand to see 'em suffer and it's hard to get 'em better.

And so that, this is also called biotoxin toxin illness.

Yeah.

Most people know that, know it as a mold-related illness, you know, more appropriately, probably you should think as a water damage building syndrome or sick building syndrome back in the '80s. But now we also know that breast implants, vaccine, um, recluse spider bites, scorpion envenomations, I know post-concussive syndrome, overtraining syndromes. All of a sudden there's a lot of things that, you know, can be in this thing. And now I've got it. Now we've got long COVID. So Why is chronic inflammatory? How is that complicated?

Yeah.

So tell us about that, the, the mechanism, cuz yeah, we'll be doing binders and some lipid stuff.

Yeah.

But then you have to figure, is there a biotoxin ongoing biotoxin? Yeah.

It's a, it's a multi-system, multi-symptom disease entity, and it's predicated usually on a genetic predisposition and exposures or, and, or, and exposure that's really significant. And the reality is it's usually cumulative exposures over time and then some incendiary event that pushes them over the edge. So this, this proverbial biotoxin or toxin bucket is filling up over time. That patient's physiology is changing. Usually we're seeing some, some hormonal shifts. We're seeing inflammatory shifts. We're seeing immune shifts and imbalances. And then eventually the bucket overflows and you flip into chronic inflammatory response syndrome. You've hit critical mass, so to speak, and now the mitochondria just kind of shut down. They go into what's called the cell danger response, and you're in what's called cell cycle arrest, where instead of the normal cell cycle, things just go from power plant mode to battleship mode. The mitochondrial genes that are present start to get dysregulated and you start to have a myriad of pathology occur, whether that be clotting events or bleeding events, whether that be inflammatory or poor immune responses. Parkinsonian genes can be activated. We're starting to be able to measure those. You can have neuronal, neuronal damage, which is typically called dieback neuron degeneration, where you start to manifest as dementia presentation. You can have floppy platelets, which is essentially an issue of the cytoskeleton of the platelet itself. So, so now you just have all these issues happening. It's clearly complicated. And the question is, well, how did the person get there? Is this just from sick buildings? Well, that's 80+ percent of the cases. Is it from an infection like chronic Lyme or acute Lyme or Bartonella or Babesia? Or is this a long COVID issue? Or is this person someone who played contact sports, had a bunch of TBIs, and then got COVID and/or a vaccine or both? And now all of a sudden they've gained 30 pounds. They have horrible brain fog, memory loss, fatigue, joint pain, and they're presenting like a SIRS patient. And it was that tipping point, that COVID infection that sent them over the edge. Because again, we know that these patients don't antigen present well, which is another way of saying their immune system doesn't communicate the handoff between the surveillance and the specialty weapons. That bridge is broken. And so you see this kind of snowball rolling down the hill and it just gets worse and worse and worse. And again, interwoven muscle activation. We see dysautonomia, but at its core, it's a mitochondrial issue. That's one of the postulated mechanisms behind the core theory around why long COVID is long COVID, mitochondrial dysfunction. I think if you look at any of the lists that you spit out earlier, fibromyalgia, chronic fatigue syndrome, like chronic Lyme, like all of these things have mitochondrial issues related to them. They all have mitochondrial pathology associated with the illness, not necessarily the reason behind it, but definitely going hand in hand. And as you get that mitochondria better, whether that's through nutritional support, some fancier stuff, like beyond the, the typical, you know, magnesium and B vitamins. Now we're getting to maybe CoQ10 and PQQ, and maybe you're doing a little D-ribose, maybe you're giving some nicotinamide riboside or NAD+. As you're getting into that mitochondrial support, you mentioned the previous episode, Methylene Blue, like maybe that's why we're jumpstarting it. You can then start to get mitochondrial biogenesis happening. You can start to get mitochondrial repair happening, turn that cycle back on, and all of a sudden that person feels better. That's a big deal, you know?

Yeah. But, you know, to that underlying this whole idea of this chronic inflammatory response syndrome is biotoxin. Yeah. And so like how many of our people who get COVID, get long COVID, are living in a moldy building or go to a moldy school or a moldy college or the workplace has mold or in our situation, healthcare, we're getting exposed to horrible amounts of chemicals. Like my office, I mean, I had come into work every morning, used to, and I'd smell all the cleaners.

Yeah.

The, the, the blue, the blue twirls in the air. Like we have like blue twirls everywhere and you have to like air that office out every day.

Yeah. But also glade plug-ins and perfumes and all that stuff. Yeah. Formaldehyde and all the fragrances and all these other things. Yeah. That's all contributing to the biotoxic burden, which is creating that baseline inflammation in that patient that now when you have baseline inflammation, that's all the way here and you get an acute COVID infection, you're, you're crossing that threshold of cytokine storm a lot quicker than if your baseline inflammation was low or your immune system wasn't already overactivate it.

And if you're not doing binders to help your gut extract things, if you're not doing lipids to help flush them through, anti-inflammatories, burning it off with things like tocambuterate, all of a sudden, like the long COVID can hang around because you're not dealing with the preexisting biotoxin burden. And that, so it, that's just chronic inflammatory response syndrome aspect of long COVID.

Yeah.

There's also, you know, one of the earlier things was all the senescent cell stuff, you know, Dr. Bruce Patterson's work showing like the, you know, you have these pieces of the COVID hanging around 6 months later, the monocytes still have COVID in there. You know, ultimately this was cells that should have been dead and turned over in 2 to 4 weeks were hanging around for 6 months and keeping this senescent inflammatory expression that was keeping people inflamed. And so all of a sudden you had other practitioners developing and using antivirals, using actually statins as anti-inflammatories for that. Not something we did a whole lot here, but I've done, done some antivirals with patients. But that's a whole other thing. Like the idea of senescent cells.

Yeah.

Which then led into quercetin, curcumin, senolytics. Senolytics.

Yeah.

And then all of a sudden, rapamycin.

Rapamycin.

All of a sudden you have, okay, so once you realize, you know, you have these dysfunctional cells, we need to burn them off. How do we get them to start replicating again? Well, let me rephrase that. How do we get them just to die out? And that became—

How do we improve autophagy, right? How do we improve our immune system's ability to clear out dead, dying, dysfunctional cells. Cuz senescent cells, another term that a lot of people know is called zombie cells, right? Yes. So these zombie cells, these dysfunctional cells, when you're young, your immune system identifies them and kills them.

Mm-hmm.

Just gets them out, right? Thinning of the herd so that you are stronger. When you get older or you're chronically ill, that happens less and less. And now you're aging and these senescent cells will literally persist and they will infect adjacent healthy cells. And now you're pushing senescence. More quickly than it should, should be pushed. And so that's where senolytics come in, is because they are trying to kill the bad cells, so to speak, or improve your body's ability to do so through a process called autophagy, which is cellular housekeeping. Then there's apoptosis, which is programmed cell death. Both mechanisms fail in SIRS patients. It's part of the mitochondrial dysfunction that happens is we see this dysregulated transcription that leads to defective apoptosis and defective autophagy. Another way of saying that is senescent cells persist and you can't do anything about it until you fix that problem. Big deal. And that's one of the things where like these other things kind of come into play. The other issue is when you have all this going on, this myriad of chaos and persistent dysfunctional cells, cells that are being lysed and their intracellular components being released into the extracellular matrix, it's identified as a danger signal. Anytime you see ATP in and around cells, not in the cell itself, but outside of the cell, that's a danger signal sent to the cell that we are under attack and something's wrong. So there's this debris field called DAMPs, or damage-associated molecular patterns, and then there's PAMPs, or pathogen-associated molecular patterns, and that's the actual infectious material. So you have persistence of virus, which is a PAMP, and you have your own cells that are dysfunctional, dying, and sending these chaos signals, which are DAMPs. Eventually the immune system that is working is gonna come in and say, I don't know what this is, but we should probably do something about it. And it presents it to the adaptive immune system and you have co-stimulation and now all of a sudden you have antibodies being made to that tissue. And if that was you, that's self-tissue presentation. Now antibodies, that's called autoimmunity. Okay. And now all of a sudden you have an autoimmune phenomenon that didn't previously exist because you had a virus. That was bad, that persisted because of baseline inflammation and maybe mitochondrial dysfunction. Now self-tissue is presented. Now all of a sudden you got Hashimoto's thyroiditis or some other autoimmune issue.

Yeah. And that gets you to a rheumatologist or an endocrinologist.

Yeah.

But the reality is you need an integrative specialist.

Yeah.

To help walk you through this, to walk back to where it started. Yeah. But it's interesting cuz the DAMPs and PAMPs, I first heard about that maybe 2012, Dr. Mark Houston.

Yeah.

Talking about vascular disease.

Yeah. Yeah.

This is how heart attacks or strokes, this is how vascular disease happens.

That's the immune dis— that's vascular, the, the one of the three finite mechanisms, right? It's inflammation, oxidative stress, and vascular immune dysfunction. And when he is talking about vascular immune dysfunction, that was what he would get into.

And so all of a sudden with this long COVID stuff, you actually got a mast cell way to look at it. You've got a SIRS way to look at. You got other very smart people looking at one subset, looking at the senescent cell aspect. And you kind of started going to that, mentioning the cell danger response basically, which is Dr. Robert Naviaux's work. You know, I kind of view, I don't know if you agree with this or not, I kind of view the senescent cell and the cell danger response as just kind of two sides of the same coin.

Yeah.

Same, basically the same thing, but different perspective. But then the cell danger response has a whole other therapeutic armamentarium because what happens is your cells get stuck and your body's waiting for like the environment to get better. So you actually back up, you don't turn cells around. And so all of a sudden you force cells with methylating agents, with nutrients. People feel horrible. Some of our patients who like, you can't tolerate a little bit of B12, they can't tolerate a little bit of folic acid, they can't tolerate small amounts 'cause it makes them herx.

Yeah.

You're actually taking these stuck cells. Now I know this. I didn't know this, you know, 5, 6 years ago. You're taking these stuck cells, forcing them to replicate and making, having a more of a cytokine response. And they have a quote-unquote Herx response because they're stuck.

Yeah.

By trying to keep them there.

Yeah.

And all of a sudden you have a whole other group of therapeutics that address that aspect of it. And I've got a lot to deal with, a lot of people at this stage now where ultimately when you fix everything, the nervous system plays into this. And because of people's nervous system trauma, limbic kindling, or the, you know, polyvagal theory or different ways of looking at it because the nervous system doesn't realize the body's safe. It's keeping you stuck in this. Now you have to do memory training.

Yeah.

Memory training. So that's, and you kind of work people through this and get to the point where they're still stuck. It's like, well, now we've dealt with this. Now we need to retrain the nervous system.

Yeah.

And the point I think to this is there's people. Before you go, real helpful advice without the hype. If that's what you came for, you want the next episode too. So subscribe now wherever you listen. And here's how you can help someone else find the exact same thing. Leave a quick review on Apple, Spotify, or wherever you get your podcasts. One line from you could change someone else's health. Thanks for listening.

And sometimes do that in the opposite order. Sometimes start to work on the nervous system first or even concurrently.

Well, it depends on them. I've had patients who can't tolerate anything. They eat like 3 meals.

Yeah, same.

They can't, like they react to cellulose in the capsules.

Yeah, same.

And it's like, okay, I, we need—

You gotta work on the nervous system. Yeah.

That's where I, there's, I usually don't start there cuz I got a lot of other things to do. But the people who literally, I can't drink water without reacting with it sometimes. I had one young lady who got, worked with someone else. I'll probably be a nature to be honest with you, but someone else gave her NAC, had a near-death anaphylactic response, messed her entire system up. And it took us like a year and a half to get her to the point where she was actually able to tolerate more than 3 foods and take, start taking supplements again, and that was like resetting the nervous system.

Yeah.

And it took a while to get to the point, but the point is like, this all falls in this world of, yeah, long COVID.

Yeah.

And all of a sudden, like, you have people doing these individual specialty things and we're here, like, I'm just trying to take care of people.

Yeah. The other thing about the cell danger response is that when that cell gets into cycle arrest and stuck, there's a component of the immune system, white blood cells called macrophages that get into an M1 state, which are inflammatory, and you can't get them into that M2 anti-inflammatory state. So you have to nudge them along. That's a problem. Because that's what happens to a lot of these people's brains is that the M1 inflammatory state just winds up wreaking havoc on their neurons. Two, they go into an inefficient fuel burning state called aerobic glycolysis, also known as the Warburg effect. So in essence, they develop insulin resistance and dysglycemia, and, and it may have nothing to do with their lifestyle due to toxicity. And that leads to even more inflammation and even more immune dysregulation, and it just becomes self-potentiating. All the autoimmune phenomenon that we talked about as well. And then there's the latent reactivation of, uh, or the reactivation of latent viruses and other infections, including Lyme, including Lyme that we see. I mean, these are all the proposed mechanisms behind why long COVID patients feel like garbage, right? Like there's, it's literally like dominoes and they're just one knocking down the next, knocking down the next. You have to figure out what is predominantly going on in that individual. And that requires testing. And it's not basic. It's expanded testing. It's functional lab testing. You have to understand what it means and what you can do about it. And then you intervene and then you clinically correlate and you see how they do and you follow the objective measures over time. Is this EBV reactivation? Is this HSV reactivation or HHV-6? Is it chronic Lyme or BART? Are they biotoxin? Is it time to support their mitochondria? Do we need to do limbic retraining now? Is this autoimmunity and I need to throw some LDN at this and work on their gut and make them gluten-free? Like, you just keep going and doing all these different things.

Yeah. And sometimes you get stuck and you're like, hey, you have these positive autoantibodies and your gut's a wreck and you have to use like a peptide, like a BPC, thymosin beta-4, you know, to help heal the gut and get them to the next stage. I just finished working through that with my daughter who had positive celiac antibodies.

Yeah.

And I'm caught it super early. I mean, you've talked, you know, yeah, you know about how this works, right? I do. Yeah.

My daughter has celiac.

Yeah. And basically it took us 3 months and retested her and it was negative. 2 weeks ago.

Yeah.

And just removed gluten because we do homemade sourdough stuff at home. And there are a few extra things, obviously doing a lot of other things, but one of the things I know she needed was a little TB4 and BPC-157. And it was really cool to see how her positive celiac antibodies went away. But the point is that, you know, so these are the people we work with, but again, how many people have access to this? And you have to work with someone. So that's where it gets difficult. So what's happening now is, and these are, these are resources that need to be out there.

Yeah.

That we'll probably put in the show notes whenever, wherever those go. There are places now just giving people lists of try this, like naltrexone, like fisetin, like rapamycin, like GLP-1s, like orovaroxaban. So I want to, next episode 3, I want to start walking through some of these.

Yes, sure.

Because these are all things we've used for years.

Yeah.

And for different reasons, but now we're going out there and the unfortunate reality is some people are just going to need to take a list like this to their provider to work through it.

Yeah. And hopefully it needs to be overseen though. Like that's the key.

Like you can't just really, yeah.

Don't just dive into this stuff. I mean, like, let me refrain from saying that. You can take vitamin D, you can, you can quercetin, you can take basic stuff, but like even quercetin, for instance, like it's nuanced. Quercetin is a bioflavonoid. Quercetin comes from like capers and red grapes. Quercetin is, or that's resveratrol. Quercetin comes from like apples and onions. And like quercetin is one of these things that's cardioprotective and anti-inflammatory, and it's a zinc chaperone and it does a lot of cool things and it's a mast cell stabilizer and I take it every day. But my wife cannot take it because it makes her horribly anxious and it's just a basic flavonoid from food. Why does it do that? She has a COMT SNP and it's a methylation SNP that affects how she processes catecholamines and quercetin will slow it down. Of course it'll slow it down even more. Hers is already slow at baseline, so her dopamine, her adrenaline, her noradrenaline stays even higher if she takes quercetin. So again, there's nuances to it. So the goal is to educate so y'all understand. The goal is to take what you can from this and take a few starting points to your practitioner and say, can we work on these things? Can you manage these things? Can we see how I do? But have some oversight so you don't hurt yourself, you know?

Agreed.

Yeah.

So the second episode was just the bigger picture of how different groups are looking at this and how the people on the ground are actually implementing it. I'm in working with someone and then Episode 3, we're just gonna kind of start going through a list of things people see online.

30 interventions.

Yeah. Talk about what we've done. Yeah. We're not gonna go through all of them cuz you know, the ones that are out there are like 30+ things.

Yeah.

But a lot of them.

No, it's a good list.

Yeah. I think it just to walk through them and to give people information cuz ultimately people are gonna have to start trying things. And I think we'll start with the things we've seen the biggest, like literally, wow, that was a game changer.

Yeah.

Cuz there's a lot of those things that can be really cool game changers. So take care. We'll talk to you soon.

See you later.

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