Addressing Long-COVID: Data-Driven Learning Model for Practitioners and Patients

As we find ourselves entering this fourth year since the world was first gripped by COVID-19, on an individual and practice level many of us are still grappling with its post-viral after-effects (long COVID). Drs Patrick Hanaway and Kara Parker, as well as my long-time mentor and former IFM CEO Laurie Hofmann, join me on this podcast to share the important work they have been doing in building practitioner tools and training to address this ongoing challenge (check out the links in the show notes). I just really appreciate their doable, data-driven, and continuous-learning approach, as I’m sure you will too. And if you’re working with COVID-19/long COVID patients (as all of us do, or will, at some point), you’ll want to familiarize yourself with their patient registry so that you too can be part of that essential data collection. – DrKF

Addressing Long-COVID: Data-Driven Learning Model for Practitioners and Patients

Official reports place the number of people who have had COVID at over 100 million globally, yet it’s likely that number is actually closer to 200 million. We also know that 15-30% of COVID-19 patients continue to have persistent symptoms weeks, months, even a year, later. These manifestations of COVID-19 effects continue to show up in our practices, and of course in the lives of the individuals that bear their burden. Yet there have been no widely disseminated clinical practice guidelines that practitioners can turn to.

Fortunately, functional medicine has tools. By taking a root-cause, systems approach to shoring up an individual’s resilience, as well as using targeted antiviral, tissue healing, and anti-inflammatory therapeutics (among others), functional medicine practitioners have measurably improved patient outcomes. That established functional medicine patients fare better when they encounter the SARS-CoV-2 virus, is an added benefit.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald:  Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And of course, today is no exception. You can see that I am here with three amazing people, if you’re actually watching this on our YouTube. If not, I am going to tell you who I’m with. After I get through that, I’ll tell you what we’re going to talk about. Okay, so Dr. Kara Parker is here. This is my first time getting to be with another Kara. She’s a board-certified family doc who’s been practicing functional and integrative and lifestyle medicine at Hennepin Healthcare with a low resource population for 20 years. She’s an educator at IFM and has worked with programs teaching functional medicine to Department of Defense and VA practitioners.

She’s the medical director of Whittier Clinic Group Medical Visits program, which she founded in 2015. She’s created and run group medical visits for long COVID since 2020, and is a consultant for And Health on the Lifestyle component of the post-COVID recovery program. Kara, I’m really happy to have you here and just really excited to do a dive into this. You’ve been somebody that I’ve admired over in the functional medicine world for a while.

Dr. Kara Parker: Likewise. Thank you. Pleasure being here.

Dr. Kara Fitzgerald: Here. And let me pivot over to Dr. Patrick Hanaway, who has taken hosting duties at our podcast and has also been interviewed. Dr. Hanaway is a board-certified family physician trained at Washington University. For more than 20 years, he’s worked with his wife, Dr. Lisa Lichtig in clinical practice at Family to Family in Asheville, North Carolina. Patrick’s work history includes being the Chief Medical Officer at Genova Diagnostics, the Chief Medical Education Officer at IFM and the founding medical director of the Cleveland Clinic Center for Functional Medicine. He’s published extensively on functional medicine as well as teaching clinicians around the world. His current work integrates research, education and patient care, focusing on nutrition, the microbiome, and evaluating the value of functional medicine. Dr. Hanaway, it’s always amazing to be with you.

Dr. Patrick Hanaway: Thank you, Kara.

Dr. Kara Fitzgerald: And we also have a Laurie Hofmann. She’s a seasoned chief executive board chair, visionary strategic advisor who has successfully led large scale strategic, collaborative and global developmental initiatives for leading functional medicine, professional education and training organizations, also healthcare systems entrepreneurs and industry leaders. She is the immediate past chief executive officer and board chair for the Institute for Functional Medicine, where she served for 20 years. Her 30-year track record of accomplishments is rooted in health and wellness, functional medicine, public health, personalized nutrition, and science-based natural medicine. Laurie, always, always great to see you, and again, just having the three of you here is quite an honor and a delight for me. We’re diving into all things long COVID, an important topic to say the least. The epidemiology, as we’ll get into a minute, is pretty profound, and we need some solutions. And of course, functional medicine has, I think, some light to shine here. Let’s just talk about it. Laurie, what was your inspiration behind focusing on long COVID? What have you been doing? Who’s involved in this?

Laurie Hofmann: Yeah. Thanks. And Kara, thank you so much for having us. We are really happy and excited to be sharing what we’ve learned and hopefully invite people into this process with us. As you said, post COVID and post-viral syndromes are of a lot of concern. There are no standards of care as we know, no proven treatments. Thanks again for having us and the inspiration, trying to just condense the story. I think as we all saw shortly after the COVID pandemic really started, we were seeing independent root cause medicine practitioners just closing their doors. And of course, everybody closed their doors for about seven weeks. But what we noticed is that root cause medicine practitioners seemed to be struggling to know what their value proposition was during COVID. Through Ovation Lab and my partners Tom Blue and Andy Crosby, we really galvanized this whole series of workshops and training programs and built care paths, and really help people independent root cause medicine practitioners understand how they really had a central role to play in keeping patients healthy and even working with mild symptoms of COVID.

Well, that led right into starting to see patients who were not recovering, and then we all came to understand the term long COVID. I had the privilege starting I think about in November of 2021, and then formally a year ago in January of having And Health, a company that Tom Blue has been doing some work with, and they’re a disease reversal company working with employers and health plans to really bring a virtual disease reversal, root cause medicine program to a variety of complex chronic illnesses. They became enthusiastic about supporting our effort to develop an approach and framework and then a program and protocol for assessing and treating post-viral syndromes and specifically long COVID. That was both the inspiration and then the encouragement that we’ve had, and frankly, the funding support and the privilege I had was to really choose and select and invite from a wide swath of practitioners and physicians and researchers to come together in a working group to really think about, scour the literature and begin to develop this approach and framework that I mentioned.

People, including Kara Parker and Patrick Hanaway, Christine Burke and Michael Stone and Tom Williams, and Bob Sheeler and Heather Tick. There’ve been quite a number of people that have been involved as well, as you’ll hear from Patrick, in us really looking at the researchers and research that was out there that was really taking a look at not just symptoms, but potential subtypes and mechanisms. Again, it’s been a thrill for us to have the opportunity to dive deeply into this. Maybe the other thing I’ll mention, and we can dive more into this a little bit later, the other thing we thought that was really important is that we knew that there’s so much that’s emerging still around post-viral syndromes that we felt it was essential for us to be able to track outcomes. In collaboration with National University of Natural Medicine in Portland, we developed a red cap patient database and our instruments, as we’ll get into, allow us to track a variety of different outcomes measures using validated tools.

Dr. Kara Fitzgerald: Awesome. And we’ll link to as much of that as we can, maybe the patient registry and how clinicians can get involved, all of that, we would really love to forward the work that you’re doing. The only thing that I wanted to comment on with what you said is that initially when COVID landed here, it was in the functional medicine world that we were rallying to have to figure out how to think about it and going into the literature and looking at SARS and MERS and how the heck do we even arm ourselves with some rationale, some structure of intervention before vaccines, before Paxlovid , et cetera, et cetera? And Patrick was a part of those conversations early on where we were very actively trying to figure out how to put our arms around this extraordinary pandemic.

And then the vaccines happened, and then there were some medications. And I know that was when we got a little bit quiet for a while. Not that we were any less thinking about it, but then long COVID began to emerge. And this, I think, is we’re just very much needed. And Patrick, having your brain wrap around the mechanisms and the various interventions that we can start to tease out, and some of the labs, and just how we can use this functional medicine framework to address this extraordinary burden is just really essential. I’m grateful for your work and I’m grateful for all the people. I’m grateful for the four of you here and for everybody who’s just stepping up to embrace this and walk it through and help us see it. Talk to me, Patrick, about what long COVID is, the epidemiology behind it, and then we can move into talking about what you guys are doing your program.

Dr. Patrick Hanaway: Right. There’s the definitional aspect, that’s looking at a post-viral illness and recovery from it. And we can go back to the Spanish flu of 1918. I learned that my grandfather actually suffered from that in World War I and his long-term sequelae in his life were related to that. We’ve learned about it more in the eighties talking about ME/CFS and unfolding there of post-viral processes. I remember, Kara in April, we’re like four weeks into it, and we are talking about post… It wasn’t even called COVID at the point in time, SARS-CoV-2. What about the post-viral impact of this and how do we think about it? And we began to think about it from a functional medicine perspective in organizing that. And obviously things have unfolded since that time, but we were aware that this would be an issue from a month into it. We could see that.

And now we have the data epidemiologically, where as of two weeks ago today from the CDC 103,268,408 people have had reported COVID, but the numbers actually are probably closer to 200 million. And what we see is that people continue to have symptoms 15 to 30% at a month. But what we’re really concerned about, which is where the definition is, what we’re really concerned about is at three months where that number’s still six to 10%. Those numbers even at 5% are 10 million people having issues at three months. But more importantly, at 12 months, we still have one to 2% of the people. A very conservative estimate is two million people. The other considerations are as much as 4.8 million people at a year (after having COVID) still having functional loss and deficit that’s going on. We can see the issue is big, and as we know, most people don’t think about it from a systems biology standpoint, from a root cause standpoint.

They think about it from a, “Oh, you have a breathing problem loss, I’ll send you to a pulmonologist. Or you have a balanced problem, I’ll send you to a neurologist. Or you have a neuropsychiatric issue going on, depression, anxiety, or dementia, I’m going to send you to a psychiatrist because this is probably all in your head. Or you’re tired, oh, maybe it’s all in your head.” These things, instead of looking at the mitochondria and the underlying physiology of what’s going on, it’s siloed. And we recognize that doesn’t really work.

And we’ll talk more about the great article in Nature Medicine from the patient-led research group, and the final author was Eric Topol, who put his imprimatur  on the whole thing. But the data there, even as they go through it and they look at it and these epidemiologic aspects, and they talk about mechanisms from a big view, but then they silo all the treatments instead of how do we work with people, the whole person and their lifestyle and what’s going on and inflammation and damage? And we’ll talk more about the mechanistic aspects of what we see as we go forward here.

Dr. Kara Fitzgerald: Certainly the matrix, the functional medicine framework lens obviously lends itself to working with this.

Dr. Patrick Hanaway: Exactly.

Dr. Kara Fitzgerald: And what’s the program framework now?

Dr. Patrick Hanaway: The program framework is that we’ve worked with the studies on looking at the mechanisms and pathophysiology that are there. And what we see in the big picture view is we can break it down to there is acute that emerges to chronic inflammation and there is tissue damage. Both of those components need to be dealt with. And when we get down the next level deeper, we say, “Okay, well, we’re going to work with chronic inflammation, but we’ve also got to deal with, there appears to be some viral persistence that goes on.” And we don’t know if it’s 10% or 40%. We know it’s there and we need to deal with it, so we’ve got to work with antivirals and things of that nature. We know that there’s a reactivation of things like Epstein Barr virus, which is the most common finding from Iwasaki at Yale doing immunophenotyping. But Epstein Barr’s not the problem, it’s just the uncovering of the immune dysregulation.

We’ve got to help the immune dysregulation. We know that there’s issues with the microbiome that are predisposing factors from the work of Su et al at the Institute for Systems Biology, led by our friends, Jim Heath and Nathan Price, and of course overseen by Lee Hood. And so, we’re seeing these aspects and how do we put them all together? We look at mitochondrial dysfunction, we look at what’s happening with the microbiome, we look at what’s happening with immune dysregulation and immune treatment that’s going on. And we also look at the tissue damage, particularly looking at the endothelium in the role of the glycocalyx and how that has an impact on ACE-2 mediated damage. You got to take care of the damage.

And what we see, even from HIV, using that as an example, is that even as we get rid of all the viral load, there’s still a long-term consequence that goes on. We need to deal with the immune dysregulation and the damage that’s occurring. And so, that’s where we focus and we focus in a way that highlights the lifestyle approach, like the nutrition as we know, tap root, how people deal with stress, emerging understanding of vagal tone and vagal stimulation, sleep, graded exercise, don’t push them too hard, and then targeted supplements, targeted therapeutics that we’re using. That gives you the basic framework of the program.

Dr. Kara Fitzgerald: There’s plenty of people though, who don’t have any identifiable viral load, but the approach isn’t necessarily going to differ that much once you get into the broader lens. It’s that initial antiviral intervention that may be side-stepped, or are you-?

Dr. Patrick Hanaway: Well, we’re, we’re using a 3CL protease inhibitor, a natural one called Gromwell root that helps to treat that. Now, we’ve looked, we did a deep dive working with NIH researchers and others to say, “Can we actually identify who has viral persistence?” And we can’t. No one can. Patterson’s Group and Iwasaki’s Group out of Harvard have all tried. We can’t figure that out. We would like to subtype it and say, “We’re just going to give this to that group,” but no one can figure that out. We’re using that particular component called Tollovid, which is a three CL protease inhibitor, not unlike Paxlovid, as a part of the program. That’s one that is used early and then it’s completed. And then there are other aspects that focus on mitochondria and microbiome and immune dysregulation that we continue on as well as the lifestyle factors.

Dr. Kara Fitzgerald: Got it. Alright, Kara, Dr. Parker, what are the main components of your program? We’ve gotten some of the mechanistic underpinnings from Dr. Hanaway, but what does it look like in action?

Dr. Kara Parker: Yeah. As a practitioner, just to put it in context, if you go to cdc.gov, type in long COVID and say, “Excellent, show me the guidelines for clinical practice.” There aren’t any. There’s nothing to guide us yet that emerges on how to work with this. But fortunately, as you say, Kara, the functional medicine approach lends so well to be able to have a pathway in which we look at these things. The pillars of our approach follow that pathway, and you start with the person. You start with the story of how they got COVID and the details around that, the context of their lives in which they got COVID. And so, we have an extensive intake form that is very carefully cultivated to give us the information we want to look at around what was their life before, what are their risk factors for how they’re going to present with COVID and long COVID, and then what has happened since then?

And along with getting the story, getting the context, and getting their health factors and comorbidities, assessment forms. We’ve got a number of assessment forms that we have patients fill out at the beginning and then at one, two, and three months as they move along through the program. And that allows us to track how are they doing, but also get a sense of really specifically where they are at. And it’s been helpful because along like other conditions such as Lyme or mold toxicity, when people are so fogged, they have a hard time telling, “Yeah, it might be a little better here but not there.” And when you actually look at what they say in these forms, you can parse it out better than the person can almost tell you themselves in some ways. And so, assessments are an important part of that.

And then just what is this root cause and how are we going to address that? You follow the physiology and get curious about it, and we built this program around that. Addressing the oxidative stress and inflammation, the ACE-2 tissue damage, the neurologic damage. We start with lifestyle, which really, as you look at the matrix of, for example, diet, we chose a primarily plant-based, but anti-inflammatory diet and decided to go with Whole 30 because it’s so well organized and wherever you are in the world, you can get this information. It’s pretty easy to apply, there’s a lot of support around it. They have a plant-based component to it. And they’re starting to be studies looking at plant-based diet for healing long COVID, that’s starting to bubble up now. The reason we also chose it was when you look at who gets sick with COVID and most likely has long COVID, diet definitely plays into that very strongly. And especially how many plants do people eat versus animal products and things like that. The other lifestyle factors-

Dr. Kara Fitzgerald: Can I just ask you, diet plays a big role. How many plants versus… Are you seeing a favorable response, tweaking diet with individuals with long COVID? Are people coming in on a certain diet that is a predisposing factor to getting long? I mean, is the standard American diet as it’s implicated in everything, is that something that you’re seeing or-

Dr. Kara Parker: Yeah. That the inflammation and oxidation of the standard-based diet is absolutely is part of the setup. Not just having diagnosed diabetes and metabolic syndrome, but literally forkful by forkful, what are you putting in your mouth? How inflamed are you coming in even if you don’t have a pre-diabetes, diabetes, obesity, hypertension diagnosis. And when we look in our intake form, we actually ask people, “How healthy was your diet?” With a lot of questions about that before COVID, during and after COVID. And because long COVID symptoms are so debilitating to people, many times people, whatever their diet was beforehand, it actually worsens, even though they wish it wouldn’t because they know they feel better on a better diet. A lot of our work in treating people is to help them figure out how to do that when they’re fatigued, when they have a lot of GI symptoms.

Really clearly having that pillar, real easy to work with people on and figuring out how to do that is an important part. I call it the central part of this. And you do see when people really make an attempt and get that inflammation down with their diet, they know it and they speak to the improvement they get. I have had a number of patients over two years that I’ve worked with on lifestyle for long COVID. Diet’s the number one thing they call out, when they’re actually able to do it, helps them. And that was before we pulled together these targeted supplements and added those in addition. We’ll talk about those… But diet is absolutely cornerstone, step one.

There was a study just published in February 2023 looking at lifestyle and predisposition to long COVID. It actually was part of the nurses’ health study data. And they took the lifestyle from 2015 and 2017 and associated it with if you had two unhealthy lifestyle behaviors, you were overweight, had a pro-inflammatory diet, aren’t sleeping well, aren’t moving, sedentary, smoke or misuse alcohol. If you have two of those, you have a 50% chance greater incidence of having being diagnosed with long COVID.

Dr. Kara Fitzgerald: That’s really interesting to me.

Dr. Kara Parker: You can imagine the unwind of that. There’s reasons the physiology is driving that, and then it’s our job to help really specifically unwind that. Another component is addressing stress. And one of the labs that associates with long COVID is low cortisol. I work with a really low resource population, very low social determinants of health. And so, the chronic stress and that people bring into COVID, let alone during COVID and whatever their story was with how sick they got. And then in the recovery, if you have lower cortisol and really can’t dampen that inflammation, then that correlates with long COVID. Helping people really address their stressors and on a variety of levels is part of the program as well.

Dr. Kara Fitzgerald: Are you using Cortef or something like that for these low cortisol folks? Just out of curiosity?

Dr. Kara Parker: We haven’t added that as part of the program, but that’s part of the personalization, depending on the person’s at. And so, lifestyle, movement, another important pillar. And with post COVID conditions, people a lot of times have post exertional malaise. They’re just not exercising the same way as they were before. We have resources to help tailor so that people move and do get the benefits of blood flow and exercise, how it hits that web in functional medicine. It addresses everything from helping mitochondria, to detox, to basically all components we want to address. But you have to do it, really, in a tailored specific way for people dealing with severe post exertional malaise, otherwise you’re going to set them back just like a person with myalgic encephalitis.

Dr. Kara Fitzgerald: It’s going to be some really basic movement?

Dr. Kara Parker: For many. And what I find on the program though, is once you get the inflammation down with diet, and especially the targeted supplements, I’m getting feedback from patients all the time that they’re now able to move more and how good that feels to them, but also it’s a marker of their stepwise improvement. I would say lifestyle is that central pillar of the program. And then we also go in a targeted way to look and deal with mitochondrial dysfunction, which is something that in standard of care medicine, oh my gosh, I have a easier time teaching my patients what mitochondria are and how they are to deal with than I do with my colleagues. But for COVID and long COVID post-viral syndrome it’s a major player. And many of these things that we’re using in our program target the mitochondria. We certainly have people on coenzyme Q10  there. A lot of the lifestyle is going to target that as well.

Dr. Kara Fitzgerald: How are you dosing it? Are you using very high doses or relatively modest amounts?

Dr. Patrick Hanaway: Moderately high, and quercetin as well. And what I was just going to say earlier was the nature medicine paper, that Topol authored, indicates that a third of the people who have post COVID don’t have any preexisting conditions. But, Kara just pointed to it, they do have the risk factors that are going on. And this imagining that it happens out of nowhere, and it doesn’t happen out of nowhere. It happens because there’s an imbalance and then it’s playing off of that imbalance.

Dr. Kara Fitzgerald: By the way, folks, I will absolutely link to the nature paper and it’s just really amazing. It’s worth your read. It’s worth your read if you’re a clinician and you’re addressing this in practice, I think it’s an amazing framework and it’s also worth it if you’re somebody struggling with this and want to understand a little bit better this systems lens.

 I just wanted to say, I have a couple of thoughts. And before I get into my thoughts again for show notes, you guys we’re going to link to where this program is, how you can find them. Certainly as people were listening to you speak, Kara, they were wanting to access this. I know it. And so, all of that will be available to you over on the show page. In our patient load, the people who come to seek us out, we know we see elevated Epstein Barr titers. I mean, routinely we’re looking for those and we see them in our patient population. We see low cortisol. I mean, all of this stuff is de rigueur in functional medicine. We look at it time and again. And so, as I’m reflecting, listening to what you guys are teasing out, I’m thinking about long COVID in my patient population who have these pieces, and I haven’t seen it a lot.

And I’m wondering if you are… And this is because they’ve been doing their functional medicine work for a long time. I mean, that’s the difference. We’re building in some resilience to this vulnerable population. I’m thinking one woman in particular who I just met with recently, and she’s got a little bit, but if she hadn’t found functional medicine 6, 7, 8 years ago, she, among other people that I can think of… Actually, myself included, I reactivate Epstein Barr – or, I have… We would be seeing it in our patient population. I guess one of my thoughts are… And it’s probably not logical at this point, but is it something interesting to see whether functional medicine was working the incidence of long COVID and in functional…? Yeah. Yeah. Go ahead again.

Laurie Hofmann: I can comment on that. I was just going to make an overarching comment and then Kara, you and Patrick can chime in. But as I was talking with functional medicine clinicians early on to really understand who is seeing patients with long COVID, many of them were like, “Oh no, we’re not really seeing too many of them.” And we started to have this conversation and recognize exactly what you said, Kara, which is that if they were established functional medicine patients, they were doing pretty well and we weren’t hearing so many reports of them developing long COVID. Now, as time has gone by and there are more reinfections, which I’m sure we’ll address here, the picture is changing. But you’re exactly right, there is a very important there there, in terms of the way in which functional medicine patients have just done better.

Dr. Kara Fitzgerald: Yeah, go ahead, Kara. You want to say something?

Dr. Kara Parker: Yeah. In my primary practice, I have about 1000 people on my panel, and I have had two people hospitalized with COVID, nobody die and very little long. And when I look at what we’re using to treat, I’m like, well, the lifestyle plus basic supplements my people have been doing for a long time to the best of their ability. I think that matters. We really have to note that it matters. The patients I get for my long COVID group visits are people of the whole system of our county hospital here in Minneapolis. And when I look into their medical history and the lack of care and the lack of just the things they come in with, the comorbidities, mental health, comorbidities, lack of nutrition, high stress, no supplementation. And it’s no wonder that people are falling so deeply into this. The setup is there.

Also from a mental health standpoint, there’s just published in January, article by Wang that looks at people most likely to get post COVID. If you have two of anxiety, depression, history of trauma, distress during COVID or loneliness, so high distress scale or loneliness, two of those gets you a 45% increased chance of having a post COVID condition. And it’s like, well, that is a big risk factor. And especially if those things are untreated and really active at the time you get COVID. Point being, I see it in my own practice every day that patients who have done these things that reduce risk factors have reduced risk factors. It’s actually not rocket science. Yeah, it’s physiology.

Dr. Kara Fitzgerald: I just have two housekeeping questions, almost. I’m curious what labs you’re looking at. And I know I want to say that I appreciate the simplicity of what you’re creating and delivering. I absolutely appreciate it. And Kara, I just admire the work that you’re doing, bringing this to everybody. But I am curious if there’s some cornerstones, there’s some really workhorse laboratory evaluations that you’re going to be getting, and maybe you and Patrick can both speak to that. And then the other piece I’m wondering is how much are you leaning on coaches? I mean, that’s got to be a big component of-

Dr. Patrick Hanaway: I’ll grab the first one and I’ll let Kara grab the second one. Because as you know, I have a little bit of experience with labs. And we looked at this and it’s like, can we really parse it out? Can we use it to be able to determine which treatment approaches are going to be helpful for which individuals? And what we found is the immunophenotyping data from Iwasaki says, we can figure out 96% predictive value, who’s got long COVID by looking at all their cytokine markers and looking at those flow cytometry markers. And we can figure it out by 95% predictive value if we just listen to their clinical story. It’s like, okay, well, so that’s not very helpful. Then we go and we look at, well, where’s it parse out? And we’ve already talked about elevated Epstein Barr titers and we see 50% depression of 8:00 AM cortisol levels.

But as you said, those are not uncommon at all, and they don’t actually drive specific treatment recommendations. While those would be considered optional things to look at as confirmatory, our labs are really quite simple. They’re working to ensure that there’s not something else going on. Do you have severe hypothyroidism? Let’s look at your thyroid labs. Are you anemic? Let’s look at your CBC. Let’s look at your CMP and make sure you don’t have some significant electrolyte imbalances or renal function problems. Let’s look at clotting factors of D-dimer and fibrinogen. Let’s make sure you don’t have diabetes. We’ll look at a hemoglobin A1C and look at your CRP to see is your inflammation out of control? Those things would all determine other kinds of therapy that would be necessary that are in the realm of risk factors for people who get it.

But it’s going to say, “Hey, you got some other stuff going on. We got to treat that first and then we’ll come back to this.” But for everybody else where those basic laboratories are normal, we’re using this similar approach. Now, we do have some interest in looking at some esoteric, what’s happening with the microbiome, pre/post, and looking at metagenomics and virtual metabolomics, but that’s more of a curiosity/exploration/hypothesis-gathering rather than a specific treatment recommendation. Because on the microbiome side, we are including a spore-based based microbiotic and prebiotics as well.

Dr. Kara Fitzgerald: And that may inform… I mean, you may actually find some biomarkers that can help you type and all of that with the -omics investigation at some point, but it’s probably not informing your treatment so much right now about. What about autoimmunity? Can one of you speak to that? ANA is up in-

Dr. Patrick Hanaway: The data from Iwasaki at Yale who’s done a lot of investigation, and with our group looking with immune and looking at a COVID phenotyping analysis, we don’t actually see autoimmunity as a driver of it. We do see it unmasking autoimmunity in people, and we do see people who have autoimmune disease as a risk factor having more problems, but it’s not as though COVID itself, SARS-CoV-2 is driving autoimmune problems, and there are no specific autoimmune markers like an ANA—and we’ve looked at that—that are predictive for this population,

Dr. Kara Fitzgerald: Which actually must come as a relief for people. I mean, there was so much anxiety around that, for some and not for others, perhaps.

Dr. Patrick Hanaway: I agree.

Dr. Kara Fitzgerald: Yeah. Did you want to comment anything, Dr. Parker?

Dr. Kara Parker: No, just always good to not have autoimmunity specifically involved. That is a relief. It’s a relief as a practitioner too, honestly.

Dr. Kara Fitzgerald: Yeah, yeah, yeah. There was tremendous anxiety around that. Did you want to… Sorry.

Laurie Hofmann: Have Kara talk about the group visit component, which is enormously important, and coaching. But I do want to say, or we don’t want to leave an incorrect impression that as Dr. Parker said, that lifestyle and nutrition and diet is very much at the center of this, along with all of the other important lifestyle components and those things that specifically relate to post-viral conditions. But also, when this team really came together, we were able to invite them to go out and really take a look at: are there targeted specialty nutritional supplements that we might select specifically to address our understanding of the primary drivers and perpetuators of long COVID? And as Patrick said, those are primarily ACE-2 tissue damage and immune dysregulation and inflammation and disruptions to the gut microbiome. And so, the team did choose completely independently, with not being seeded with anything, very specific products.

I would say that the other supplements, even mentioning co-enzyme Q 10, for example, there are some other foundational supplements that are recommended, and for many of the functional medicine patients, they’re already taking them. What we have found, and here’s where Kara and Patrick can really talk about this, is these specialty supplements have made a huge difference. Now, this is where we’re collecting data in the registry. We’ll be evaluating it, we will be learning more, but I’m sure Kara and Patrick can both just give you a couple of examples of it’s helpful that, as Kara has said, front end loading and really working with people with their diet first. But then we have found that we have needed to have something else to change the trajectory. I think more than 50% of the patients that are in our registry have had long COVID for a year or more now.

Dr. Kara Parker: Patrick, you want to go do the supplements, what they are?

Dr. Patrick Hanaway: Why don’t you talk about the coaching piece first and then I’ll talk about the supplements?

Dr. Kara Parker: Yeah. Well, coaching, I think that’s really what you’re talking about is we can have great information on how lifestyle and changing these things plus taking these supplements will give some improvement to your post-viral symptoms, but how do you get people to do that? And it’s humbling that as a practitioner, seeing patients one-on-on once a month at the most, probably, to a couple times a year. Group visits, we get to see them weekly. But the healthcare change happens day to day at home, and that’s where it’s ideal to use coaches. There’s functional medicine coaching academy. A lot of people listening are practitioners and have access to health coaches. We don’t have health coach access here at our institution. We don’t have one on staff, but we use students and their final project is doing a four to five week health coaching, and I grab them.

They’re going to be working with our long post COVID patients with anti-inflammatory diet, whole 30 diet, starting actually on Monday. I think it’s really needed because taking the knowledge and applying it in your life with post COVID in particular, when people are needing a lot of support and aren’t really as able to be in their lives. How do you get to the grocery store when you’re so tired there? There’s a lot needed to figure the details out of applying the program, so it’s a fabulous way to use a health coach.

Dr. Kara Fitzgerald: It just strikes me as it has to be just essential, and I’m glad you’re grabbing the students. That’s what we do here. We have an internship program with CNS nutritionists, and absolutely they’re helping us in the trenches. Yeah. Okay, Patrick?

Dr. Patrick Hanaway: Well, Laurie talked about the foundational supplements that were used in the foundational tools, and that is first working with this 3CL protease inhibitor, Tollovid, developed out of Israel and something that we looked at and we said, “Well, can we use some other antiviral? Would that work?” But we continue to find in our beta testing that this is a critical tool for people, and it seems to be acting in twofold. One, around those where there is a viral persistence, but it also seems to be helping with the viral reactivation of the herpetic viruses like Epstein Barr. People are feeling better with it. And if you had COVID for less than a year, we give it for 10 days. If you had it for more than a year, we’re giving it for 20 days. And then we’ll be evaluating people after that period of time.

I’ve had patients where I’ve given it for 20 days and they feel great, and then by day 25 (after stopping) they’re like, “Okay, I was 90% better, now I’m 80% better, and by a month and a half out now I’m 50% better.” And it’s like we reapply this 3CL protease inhibitor. That’s one agent. We use an anti-inflammatory and the anti-inflammatory that we’re using. We looked at all the different kinds of things that are available around curcuminoids and different aspects. But we find if you recall that one of the pathways on the NLRP3 inflammasome that was affected was beneficially helped by Chinese skullcap, scutellaria baicalensis. And so, we’re using an anti-inflammatory that has that as the primary focus of it. It’s got Boswellia and curcumin and other aspects in it as well. But that’s where the focal point of the anti-inflammatory is.

We are working with a rhamnan sulfate from algae that is helping to be able to help with the vasculature and the endocarditis that’s gone on that the tissue damage, that’s primarily ACE-2 mediated. You know this one well, Kara. You were talking about this very early on, what we need to do, and we’d like to think that we don’t have to continue to do that because there’s not persistent infection, but the damage has already occurred, and so we have to take care of the damage that’s occurred. And then finally, we’re working foundationally with a spore-based probiotic initially and then with a prebiotic to help bring shift back to the overall microbiome. Those are the really focused aspects in addition to those things that are going to be able to help the mitochondria, help the overall balance using an omega-3 fat, using quercetin, using magnesium, things that are baseline for us as functional medicine practitioners.

Dr. Kara Fitzgerald: Yeah.

Dr. Patrick Hanaway: I want to say one other thing. And that is that we looked at, well, what about mast cell activation? And do we go with luteolin and other aspects there? What about other considerations in terms of mushrooms and activation of the immune system and immunomodulation? What about monolaurin, and do we consider those things? And so, those are all in the potential for personalizing it as we go forward, but we didn’t want to overdo it. And what we’re finding is that a lot of people are getting better with this foundational approach that we’re doing. We’ll have other tools that we can use in the future as we personalize, but we don’t need to do that right upfront.

Dr. Kara Fitzgerald: I get it. And I appreciate that. I appreciate it just in this population in particular, we just need to keep it simple. And so, the fact that you’re getting good outcome with this simple approach by functional medicine standards, there’s still a lot going on. Vitamin D, vitamin D has gotten more attention that probably any other nutrient, is this part of the core vertical?

Dr. Patrick Hanaway: Didn’t mention that. It’s in there.

Dr. Kara Parker: That’s in the protocol.

Dr. Kara Fitzgerald: I would be pinged on that.

Dr. Patrick Hanaway: We do measure vitamin D to figure out at what levels do you need. If your vitamin D levels are in a great range, you don’t need vitamin D or any more than you’re currently taking. And so, it’s really a stratified approach.

Dr. Kara Fitzgerald: Good. Okay. And they’re vitamin D levels around 50 or so, 50 to 70?

Dr. Patrick Hanaway: At least 50, yeah.

Dr. Kara Fitzgerald: Yeah. Okay. Anything to add to that? Kara, did you want to say anything?

Dr. Kara Parker: Yeah, I think thinking about what patients experience when they put these products in their bodies. I’ve worked with people on lifestyle for two and a half years now-

Dr. Kara Fitzgerald: Let me just jump in me, I’m sorry. I want you to talk about outcomes. I want to hear the individual pieces from the patients, but you can also just fold that into the data you’ve been collecting and what you’ve actually been seeing in the registry.

Dr. Kara Parker: Yeah. Well, qualitatively, I would say that right now I have a group of 13 and every single one of 13 people, as they’re on week three or so of this targeted supplement protocol Patrick just described, plus a requirement for them to do that is that they’ll do their best to follow a whole 30 diet. About a month on whole 30 and three weeks on a targeted supplement. And people are thinking more clearly, their pain is down, they’re sleeping better, their mood is describably better, their post exertional malaise down. It was just really fun to hear feedback.

I had a physical therapist who works in our COVID clinic message me and say, “I’m seeing a number of your patients that are on your protocol, and how do we get this for more people? Because I’ve been working with them for a year and they are different now. They’re different.”

And including oxygen saturation. One person said, “When I go do PT, my oxygen with minimal exertion went down below 82 and they’d make me stop. Now I’m 92 or above, and I’m doing a lot more just on three weeks of adding the supplements, plus the diet.” We’re getting some real specifics like that. POTS people describe their tissues being doughy, inflammation and swelling, as well as just the tachycardia, dizziness and all that, and they’re starting to shift with the supplements and the approach. When they worked for a couple of years with experts with having salt and compressive stockings and physical therapy and doing everything they could, so it’s very encouraging,

Dr. Kara Fitzgerald: Incredibly encouraging. So great. And you, Laurie or Patrick, do you want to add to that?

Laurie Hofmann: Well, I might just say something about, and then Patrick can give some specific outcomes, statistics, but we talked about the Redcap patient registry. And so, the intake form that Kara mentioned earlier, we adapted from the WHO Global symptoms survey, and then we built this tool that’s called a timeline and progression of symptoms that, again, as Dr. Parker said, we’re looking at health status before they had COVID, then when they had COVID, what has persisted, what’s gotten better, what remains? And we look at that every month, baseline 30, 60, 90 days. But in addition, we chose two validated instruments to include in the registry, the Promis 29 and the post COVID function scale.

And we had, really, our first opportunities a few weeks ago to pull some data from the registry from the Promis 29 outcomes. And I know I was surprised, surprised that it was that good. I think something Patrick can talk about it more specifically, but one of the things that we didn’t really understand or appreciate how important it was going to be on the front end was choosing Promie 29 and the way that those domains line up with many of the mental health and other symptoms that we’re seeing in long COVID. It turns out to be a very important tool for us to use to evaluate outcomes. But Patrick, you can say more specifically what we’re starting to see from the registry.

Dr. Patrick Hanaway: Sure. Just in terms of Promis, those patient report outcome measures and as you know, have been a big proponent of Promis 10 and included in clinical practice and the work we’ve done at the Center for Functional Medicine. But what we recognized is that we needed something that was a bit more expansive than the simple 75 second, 10 questions looking at global mental health and global physical health. And so in using the Promis 29, that’s looking at measures of fatigue, of pain, of anxiety, of depression, of social disturbance, of physical health and wellbeing as well as social wellbeing. And so, all of those, we have measures of each of those independently within our redcap registry to be able to do that. And so, what that does is it helps to define…

I mean, some people are having problems with anxiety and depression, and we see a significant shift there. Some people are having problems with fatigue and we see shifts there. It’s not an outcome that is easy. But I have one patient who was incredibly healthy, doing HIIT workouts three times a week and doing these things up until he got COVID and now he can’t move, he can’t walk up two flights of stairs, but his measures look okay because his activities of daily living, he’s a high functioning corporate executive who flies around the world. But he can’t actually…. He was in a charitable baseball/softball game, and he couldn’t run from first base to second base. And this is a guy who is a triathlete. And so, he started the program and he is all of a sudden 10 days in, he is like, “I can start doing this.” I’m like, “Slow down, don’t go too fast.” But he’s got his life back.

On the outcome measure, it doesn’t look great for him because he was already pegged at the far end. But for many others who are having fatigue and depression and anxiety, we’re seeing shifts that are moving them from the fourth percentile to the 70th percentile and using the Promis measures to be able to help us with that is where we’re going. And at this point in time, it’s case studies, but we’ve got more than 50 people in the registry at this point in time, and we’re looking forward to when we have 3000 people in the registry and we can begin to parse out – people with this symptom complex, they’re the ones who actually are going to benefit the most from the 3CL protease inhibitor. And people of this symptom complex, and these risk factors, they benefit the most from this and will be able to learn how to be able to parse that.

But right now we’re in the hypothesis generation phase of being able to figure out which of the things actually work, so our approach is a little bit more protocol and shotgun-driven than would be a typical personalized functional medicine approach.

Dr. Kara Fitzgerald: Well, this is where we start. It’s just great that you’re doing all of that and then you’ll be able to stratify, you’ll be establishing subtypes starting with the case report. I mean, obviously I’m a big fan of this approach. And then you’ll be able to look, you’ll have the lab data, you’ll have some of your omics data that might help inform all of that. It’s a really good direction.

Laurie Hofmann: May I add something, Kara? Because I feel like it’s important. We have had tremendous support from industry and educators and companies who recognize the importance of this. And the statement that I hear most frequently is, “We got to do this. This is so important.” For example, the virtual group visit program that Kara Parker started, Kara you can say three or four weeks ago that’s using our program, we’ve had the benefit of having some of the BiomeFx tests donated, so we’re getting some baseline microbiome data as well as looking at the persistence of some SARS-CoV-2 fragments. It’s not just our protocol. We are really using this as an incubator. We’ve been working with a couple of labs on assays around viral persistence, as Pat Patrick mentioned earlier. And the support and the enthusiasm and the encouragement for this has been tremendous.

Dr. Kara Fitzgerald: Alright, well, as we come to the close-

Dr. Patrick Hanaway: Can I say one thing? Under Laurie’s leadership.

Laurie Hofmann: Thank you. That’s great.

Dr. Kara Fitzgerald: Amen to that. As a beneficiary of Laurie’s mentorship, I certainly appreciate that statement. Okay, so clearly you’re going to publish, it’s just a matter of when. Are you are looking at maybe publishing a case series or do you want to have something larger? That’s a question. There are multiple papers in this I can imagine. And we worked with, for our research, I have an IRB through NUNM, and I know they do a really good job over there. Ryan Bradley is awesome. That’s one question. But really more importantly, we’ve got clinicians listening to this podcast and then we’ve got patients, we’ve got people who’ve got who have long COVID. There’s folks who love on individuals who have long COVID, so how do we access you?

Laurie Hofmann: Yep. Perfect. I’ll start, and Patrick and Kara can chime in. So, what’s next and what are the important priorities for us? As Patrick said, more patients in the registry. We are in a protocol development and refinement phase, and so having more patients that are in the registry is important. Well, how does that happen? The other thing in parallel that is equally as important is I feel very passionate about the need for us to train a workforce of root cause-oriented providers who are able to assess and treat their patients with post-viral conditions. The way in which people can honestly reach out to me, I can say my email, I’m sure you’ll put it in the show notes. But there are clinicians that we’re finding that are like, “You know what? I have patients that need help and I really want to refer them to this. I don’t quite have time right now to learn myself.” We have clinicians who have been trained who are able to provide a virtual consultation. That’s one option.

Another pathway is for clinicians who actually want to be trained in this approach and protocol. They can also do that. In fact, in the month of April (2023), we’re doing a series of training workshops that will be on Zoom. There’s broad-base support for it from both education organizations and industry and other who all will be sending the registration information. I hope you will as well, Kara. And so, those are a couple of really important things that are coming up. Getting the workforce trained, getting more patients in the registry, having options for clinicians who want to find pathways for referring patients, but are not ready and able to, don’t have the bandwidth to take on. Another thing of diving into this approach. Patrick and Kara, what did I miss?

Dr. Patrick Hanaway: I feel like you got it. And Kara asked about research. We’re not focused on publishing the research. We’re focused on getting the data first, and we’re really building up this registry to be able to see. And then one of the things that I’ve found is that… And then let’s see what the data shows us. Let’s see what we’re really learning. Mentioned earlier, there were questions about should we use this? Should we use that? And we started hearing from how the patients were doing. It’s like, “Oh, that’s making a bigger difference than we thought it, we have to continue to include that in what we’re doing.” And sometimes patient starts one supplement, but they don’t have the other two and they’re getting better. It gives us information. Someone else gets two and they’re not getting better, and they get the third, and then they start feeling better. We’re listening to that and listening to the data and seeing where does it take us and what is it teaching us about what’s happening with these individuals?

Dr. Kara Fitzgerald: So, so cool. When I was preparing for this interview today, I was looking at Epstein Barr and the association with all these, the cancers, the post-viral sequelae. And the intention that you’re developing this with may serve to answer some of these other questions. I mean, post-viral syndromes have been around forever and we’ve been tussling with them in functional medicine forever. But you’re starting to really codify something that could serve not only for those acute post-viral, but the decades later potential for increased risk of cancers and so forth, that it’ll be interesting to see where this goes in the long haul.

Dr. Kara Parker: Yeah, I think I would add that if you’re a practitioner listening to this and feel like, you are wondering if you have bandwidth to learn about it, you’re already seeing it in your practice. You’re seeing ramifications of COVID and post COVID conditions all the time. And so, it’s worthwhile to learn some extra tools in your toolkit that can help patients.

Dr. Kara Fitzgerald: And it’s straightforward. I mean, what you’ve outlined here today is something that most of us, even if we’re new in the functional medicine journey, would be able to administer, I think. Thank you. Thanks so much for joining me today. It was just fabulous to have all of you with me and it’s inspiring, the work that you’re doing. Onward.

Laurie Hofmann: Kara, thanks so much for having us. We really, really appreciate it.

Dr. Patrick Hanaway: Thank you, Kara.

Dr. Kara Parker: Yeah, thank you.

Dr. Kara Fitzgerald:  My pleasure.

As always, thank you for listening to New Frontiers in Functional Medicine, where our sponsors help bring the very best minds in functional medicine, and today is no exception. Not everyone can be a sponsor on my platform, and I so appreciate the good work, relentless research, and generous support from my friends at Rupa Health, Biotics and Integrative Therapeutics. These are brands I know and trust in my own clinic and can confidently recommend to you. Visit them at RupaHealth.com, BioticsResearch.com and IntregrativePro.com, and please, tell them you learned about them on New Frontiers.

If it’s not too much to ask, I would appreciate a thumbs up and a kind review wherever you listen to New Frontiers. Thanks.

Partner, OvationLab Laurie Hofmann is a seasoned Chief Executive, Board Chair, Visionary, and Strategic Advisor who has successfully led large-scale strategic, collaborative, and global development initiatives for leading Functional Medicine professional education and training organizations, health care systems, entrepreneurs, and industry leaders. She is the immediate past Chief Executive Officer and Board Chair for The Institute for Functional Medicine where she served for 20 years. Laurie’s 30-year track record of accomplishments in Health and Wellness, Functional Medicine, Public Health, Personalized Nutrition, Science-Based Natural Medicine, Process and Strategic Planning, and Complex Dialogue Facilitation have served to advance and significantly expand the awareness, reach, and traction of functional medicine and personalized nutrition. Laurie’s Strategic Advisory Roles include: Functional Medicine, Personalized Lifestyle Medicine, Personalized Nutrition, Health Coaching, Community and Public Health, Natural Products, Health and Wellness Programs, Digital and Remote Tracking Technologies.

Patrick Hanaway, MD is a board-certified family physician trained at Washington University. Dr. Hanaway served on the Executive Committee for the American Board of Integrative Medicine and is Past President of the American Board of Integrative Holistic Medicine. For more than 20 years he was worked with his wife, Dr. Lisa Lichtig, in clinical practice @ Family to Family: Your Home for Whole Health Care in Asheville, NC and Weaverville, NC.

After 10 years as Chief Medical Officer at Genova Diagnostics, Dr. Hanaway became the Chief Medical Education Officer for the Institute for Functional Medicine (IFM) where he oversaw the development and implementation of IFM’s programs worldwide. He has taught with IFM since 2005 and has filled numerous roles: leader the GI Advanced Practice Module, Co-Chair of IFM’s Expert Advisory Board, guiding the COVID-19 Task Force and serving as a Senior Advisor to the CEO. In 2014, Dr. Hanaway worked with Dr. Mark Hyman to develop the collaboration between IFM and the Cleveland Clinic, where he was the founding Medical Director, then Research Director. He now serves as a Research Collaborator with the Cleveland Clinic Center for Functional Medicine. His research interests focus on nutrition, the microbiome, and evaluating value in functional medicine models of care. In 2018, Dr. Hanaway was diagnosed with Stage IV Laryngeal Cancer. His life has been transformed through a functional and integrative approach including nutrition, shamanic healing, acupuncture, herbs, prayer, chemotherapy, radiation therapy, community support, spending time in nature and love. Recent medical assessments demonstrate ‘No Evidence of Disease’. . . and life continues to be filled with uncertainty.

The primary focus of Dr. Hanaway’s work is to leverage his skills and knowledge to transform medical practice, through education, research and clinical care. Importantly, Dr. Hanaway was initiated in 2009 as a Mara’akame [indigenous healer] by the Wixarika [Huichol] people of the Sierra Madres in Mexico. He is chairperson of the Blue Deer Center in upstate NY. Patrick holds community fires, leads ceremonies and pilgrimage to sacred sites, and offers traditional healing sessions ‘around the fire’ at the Sacred Fire Council House in Weaverville.

Dr. Kara Parker is a board-certified family doctor who has been practicing Functional, integrative, and lifestyle medicine at Hennepin Healthcare (HCMC) with a low resource population for 20 years. She Is an educator for IFM and has worked with programs teaching Functional Medicine to DOD and VA practitioners.  She is the medical director of the Whittier Clinic Group Medical Visits program, which she founded in 2015. She has created and run group medical visits for Long COVID since 6/2020 and Is a consultant for And Health on the Lifestyle component of the Post COVID Recovery Program.

For more info on the program, protocol, registry: info@ovationlab.com

Register for practitioner training: http://www.ovationlab.com/postviralrecovery

Contact Laurie Hofmann: laurie@ovationlab.com

Nature Reviews Microbiology: Long COVID: major findings, mechanisms, and recommendations

Iwasaki (Yale)/Immunophenotyping (Science, 2022): The immunology and immunopathology of COVID-19

Institute for Systems Biology (Cell, 2022): Multiple early factors anticipate post-acute COVID-19 sequelae

Wang et al. / Nurses’ Health Study data (JAMA Network, 2023): Adherence to Healthy Lifestyle Prior to Infection and Risk of Post-COVID-19 Condition

Wang et al. / Mental Health (JAMA Psychiatry, 2022): Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post-COVID-19 Conditions

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