Diagnosing Post-Acute Infection Syndromes: Special Series from The Cohen Center for Recovery from Complex Chronic Illnesses at Mount Sinai

The information offered in this program by the host and guests is intended for educational purposes only and does not constitute medical advice from Osmosis from Elsevier or the Mt. Sinai Health System. The determination of the need for medical services and the types of healthcare to be provided to a patient are decisions that should be made only by a physician or other licensed healthcare provider.

Dr. Raven Baxter 

Hi everyone. I'm Dr. Raven Baxter and I'm your host of this episode of the Raise the Line podcast. I'm a molecular biologist and director of science communication at CoRE, which is the Cohen Center for Recovery from Complex Chronic Illness at the Icahn School of Medicine at Mount Sinai Hospital. At the center, we work to advance treatment and knowledge of long COVID, tick -borne and vector -borne illnesses, myologic encephalomyelitis, chronic fatigue syndrome, and connective tissue disorders such as hypermobile Ehlers -Danlos syndrome. 

This series of episodes is about post -acute infection syndromes, and they're characterized by persistent symptoms that last for months or even years after the initial infection has been treated. Many of these conditions are often misdiagnosed, leading to delayed treatment and prolonged suffering for these patients. Diagnosing post -acute infection syndromes is a complex process that requires a thorough understanding of the patient's medical history, symptoms, and potential underlying causes of their condition and it involves a combination of clinical evaluations, laboratory tests, even imaging studies, and sometimes even biopsies. But due to the lack of awareness and research on some of these conditions, there's not necessarily a standardized diagnostic protocol for post -acute infection syndrome. 

So, in today's episode, we are hosting three specialists, Dr. David Putrino, Dr. Amy Kontorovich and Dr. Shannon Delaney, who will join me in discussing their experiences and insights on the challenges and advancements in diagnosing post -acute infection syndromes. We're going to do a deep dive into the various methods that you can employ for diagnosing post-acute infection syndromes. 

I would like to introduce our guests. Dr. David Putrino is a physical therapist with a PhD in neuroscience. He's director of Rehabilitation Innovation at Mount Sinai Health System and he's been actively involved in developing new technologies for rehabilitating patients with neurological disorders, including post -acute infection syndromes.  He's worked as a clinician in Australia before moving to the US to study computational neuroscience at Harvard, MIT, and NYU and he served as a faculty member at Weill Cornell Medicine and Burke Medical Research Institute. 

Dr. Amy Kontorovich specializes in internal medicine and cardiovascular medicine and she holds several roles in her field, including as an associate professor of Medicine and Cardiology and Genomic Medicine at Icahn School of Medicine at Mount Sinai. Dr. Kontorovich focuses on diagnosing and managing hereditary cardiovascular conditions, and her laboratory is dedicated to understanding genetic relationships in cardiovascular diseases. She's supported by the NIH and others. 

Dr. Shannon Delaney has worked for many years doing a mix of research and clinical work at Columbia University Irving Medical Center. Her clinical research has focused on immune and infectious contributions to psychiatric disease, especially psychosis, in children and young adults. She's currently in private practice in New York City and specializes in seeing children and adults with complex neuropsychiatric presentations, especially those with suspected Lyme disease or other tick -borne diseases, as well as those with pediatric acute onset neuropsychiatric syndrome or PANs. 

So thank you, everyone. There is a wealth of knowledge in the room, and I'm looking forward to our discussion today. OK, so being that post -acute infection syndromes are quite complex, I think that it's important for us to lay a foundational understanding of what medical students can expect prior to the diagnosis. How do you approach that first encounter with a patient? 

And I will send this to David. 

Dr. David Putrino 

Me first? Sure. I think that usually what we do when a patient comes to see us with a complex chronic illness is one of the things that we try to do most frequently is to avoid labels from an early outset and just try and focus in on what are the symptoms, how do we measure those symptoms and what might be the underlying physiological causes of those symptoms. 

For instance, if a patient comes to see us and they're experiencing significant joint pain, one of the first things that we want to understand is, okay, are you hypermobile? You know, are you showing us signs and symptoms of joint hypermobility? We assess that using the Baden score and some other assessments that we use to evaluate not just whether or not hypermobility exists, but the extent of it. 

And then based on whether or not we're seeing joint hypermobility, we go down a treatment path. However, people can be experiencing prolonged pain without joint hypermobility, they can be experiencing prolonged pain whilst expressing joint hypermobility, but that's not actually the cause of the pain. It's just an incidental joint hypermobility or it could be related, but it's not. So really what we try to do initially is just understand what has brought the person to us. 

What are the most in -depth and comprehensive and informative assessments that we can do to understand underlying physiology? Whether it be a detailed autonomic nervous system assessment, a detailed metabolic assessment, what can we do to just better understand what could be driving these symptoms? And then referral to specialty care as needed whether that be working with someone like Amy or working with someone like Shannon so that we can really make sure that the person is getting the care that they need or even in some cases getting the clearance they need to begin intervention so that we can be sure that we're proceeding safely. 

Dr. Raven Baxter 

Thank you. And Amy, you specialize in understanding the genetic basis behind cardiovascular diseases, but I'm really curious to know your approach in piecing apart what is a symptom of a post -acute infection syndrome versus what could perhaps be a genetic trait, or is there a blurred line there? 

Dr. Amy Kontorovich 

Yeah, well, the fundamental process for either investigation is rooted in the patient's narrative. What are they telling you? What is the history? And what can you sit back and listen to and let them sort of tell from their perspective? Then what can you do to enhance the history gathering with focused questions?  

I think those are skills that medical students really need to hone in during their training, but listening being the most important one. It's challenging because by nature of these set of conditions being chronic, most of the time patients will come to me after they've had many, many, many years of a diagnostic odyssey and they've seen lots of other doctors who may have put a label on it. I mean, I really like what David says about not putting a label because there is something very psychologically rigid about having a label that may be the incorrect label. And if it is incorrect, it's hard to wind it back. 

There is a blurred line, to your question about differentiating a genetic cause versus an infectious cause for certain cardiovascular diseases. You could argue that all diseases have a genetic basis to some extent, but the type of genetic conditions that we focus on in our program are what we call monogenic diseases where you have a germline variant, usually a high -impact variant in one gene, that is a strong enough genetic impact to be able to cause the disease in and of itself. But there are a couple of really notable examples in cardiology where one could have a high impact genetic variant that puts them at risk for heart disease, but it takes a second hit of something environmental that then flips on or activates the disease. And that is known to be the case for certain heart conditions like cardiomyopathy and myocarditis, usually the cause in that case is a virus. So yeah, there's various strata in the investigation to try to disentangle these components. I hope that answers your question. 

Dr. Raven Baxter 

That was a beautiful answer to the question, very enlightening and helpful, I'm sure, to the medical students listening. And that brings me to Shannon. I sort of have the same question for you and I think that this is definitely a multi -tiered question because a lot of patients who are seeking treatment for psychiatric manifestations of post -acute infection syndromes -- at least in my experience as a long COVID patient -- it's been hard to find physicians that understand that there even is a psychiatric manifestation of these diseases and they don't necessarily treat it as a post -acute infection syndrome, but rather just label it as generalized anxiety or depression. I don't think that really is a comprehensive way to treat post -acute infection syndromes. So what is your approach? Have you had people come to you and say, hey, I've been feeling off and do you then say, well, did you have COVID or did you get tested for any diseases? I'm really curious to see what your approach is there.

Shannon Delaney 

Yeah, I think so. So I'm a psychiatrist that sees both kids and adults who've had many infections that can trigger their psychiatric symptoms and in particular, I see a lot of patients who've had infections such as Lyme disease or other tick-borne illnesses. Most of the time when I see an adult who presents, they often are presenting with a combination of symptoms, what we would classically call more medical type symptoms like fatigue and joint pain, and often psychiatric symptoms too, like anxiety, depression. But what most people don't know, including most doctors, is that when kids get infections, oftentimes they present only with psychiatric symptoms. 

So, the typical kid that I would see who presents to me in my clinic would be a new onset behavioral change or a personality change. This would be like a ten-year-old little girl who had like a calm and sweet personality and all of a sudden one day wakes up and she has new onset OCD symptoms and she's acting very aggressively and hitting her parents and running out of the house...so pretty radical personality changes in these kids. It's obviously a very scary thing and parents are in crisis mode because they don't understand what's happening to their kid. But this is where the knowledge base is really important, because most people don't often make the link between new onset psychiatric symptoms and infections. I think more so really in the last few years or last couple of years, I think the word is getting out and parents are talking to friends and family and they're reading more, and they understand that these conditions can present with only psychiatric symptoms.  

The good news is that more recently, I've been seeing patients earlier on in their diagnosis. So instead of seeing patients who have these new onset psychiatric symptoms and they go right to a psychiatrist and go down the psychiatric road only and sometimes get hospitalized for many months and put on psychiatric medications, I'm seeing them within the first couple of months of their illness. I'm able to do a very comprehensive evaluation in terms of medical and psychiatric histories, do comprehensive laboratory workup to really try to get to the root cause of what infection might be contributing to their psychiatric symptoms.  

So, I think that's the most important point to emphasize from my perspective to the medical students and other people in the medical community that most of the time when I see kids presenting to me after these infectious syndromes, they're presenting mostly only with psychiatric symptoms. Sometimes they'll present with a mix of psychiatric and other symptoms like fatigue and some neurological symptoms like dizziness or headaches, but I would say more than 50% of the time it's solely psychiatric symptoms. 

Dr. Raven Baxter 
So, would you say that in those cases, their treatment journey would start with you and then you would refer out to other specialists from there? 

Shannon Delaney 

Yeah, well, my goal is that we would have many doctors who kind of recognize that these particular new onset psychiatric symptoms are probably linked to an infectious or immune triggers and are able to recognize it, do the proper workup. It doesn't have to be me, but other doctors can do that too. And once the appropriate diagnosis and treatment is made, again, I'm seeing these kids a lot earlier on in their journey now and oftentimes when they're put on the right combination of antibiotics and or other medications, they can get better pretty quickly. 

What we see where the real problem point lies is when they have these new symptoms, they often will be put on high doses of psychiatric medications because there is a rational basis for that, but then oftentimes those medications make the situation way worse. In fact, oftentimes the SSRI medications, which would be the standard go-to medications for things like anxiety, depression, or OCD...they can cause a lot of agitation and even suicidal ideation in kids who have infections.  

And so what can happen is that if you're not knowledgeable about the fact that these infections can cause psychiatric symptoms, they get put on these high dose psychiatric meds, then they often are hospitalized and they go through the whole psychiatric realm of repeat hospitalizations until finally someone asks them: “Oh, have you considered that this might be PANS or PANDAS?” PANS stands for Pediatric Acute Onset Neuropsychiatric Syndrome, which basically describes these psychiatric symptoms, such as OCD, restricted eating, emotional lability, suicidal ideation...all of these new psychiatric symptoms that can happen in the context of infections. 

Dr. Raven Baxter 

What would you say is a likelihood? I mean, I'm just thinking of how traumatic the hospital psychiatric experience can be, especially for children. What do you think are the odds that anyone would know to identify that? Like, how long would they go being, I guess, not treated properly? 

Shannon Delaney 

All I can say that I am seeing a little bit of a trend in terms of change in behavior and that I am getting patients a lot earlier. That is to say, I still see a fair amount of patients who when you take a thorough history, it seems as if their initial infection was probably triggered like years ago and then they had a steadily increase of kind of strange symptoms that continued to develop over the course of months and years. And those are obviously like very difficult cases. You can imagine the emotional toll and burden of the family when they find out that maybe all these years of suffering could have been potentially prevented if just there was better education and knowledge. 

Dr. David Putrino 

I can't speak for PANS or PANDAS, but I can say that there is literature out there in the dysautonomia world that the diagnosis gap for adults is around seven years. So, it's usually seven years of other diagnoses being thrown on the table. 80% of folks with a dysautonomia or a POTS diagnosis will first receive an anxiety diagnosis, which is no longer relevant once you know POTS has been determined. So seven years is the diagnostic gap for POTS, which is kind of wild to think about. 

Dr. Raven Baxter 
That's a long time to be potentially suffering without an answer. 

Dr. David Putrino 

Amy, I don't know if there's any literature around EDS, but it's horrifying. 

Dr. Amy Kontorovich 

There might be, I mean, I can just say anecdotally that it's at least several years between symptom onset and by the time a patient sort of navigates their way to EDS when it is the correct diagnosis, they're usually first told they have fibromyalgia or chronic fatigue syndrome that comes into play again with the dysautonomia. It's usually several years before they sort of land on the correct diagnosis if in fact it is EDS.  

But I also just wanted to make a comment that in my experience, the shorter the interval between symptom onset and landing on that correct diagnosis so that the correct interventions could be prescribed, the better by a lot. The difference in outcomes that I've seen has been very, very dramatic. So when I can meet a seventeen-year-old who is just starting to become symptomatic with EDS and POTS and sort of get in there and this is the right diagnosis and this is what you have and so you need to do, I almost never even see them again because they do so well, as opposed to the 35-year-old who has been struggling for fifteen years. It's much harder for them to achieve meaningful symptom improvement after so many years of locking into that disorder. 

Dr. Raven Baxter 

Wow, I'm really speechless. I truly don't know what to say. I feel like that just speaks volumes to the importance of initiatives like this to raise awareness around these syndromes so that doctors do understand what options are available to consider in addressing patients' concerns and issues.  

So, if you could have a pie in the sky projection of what the future of diagnosing post-acute infection syndromes would look like. What would that be? Like, in an ideal healthcare practice. 

Dr. Amy Kontorovich 
You know, I can't claim to be an expert on this overall category of conditions – post -acute infectious syndrome. My area of expertise lies within that post-infectious disorders umbrella, it lies in EDS, Ehlers-Danlos syndrome, and dysautonomia. 

But I think the pie in the sky vision for how to improve patient care is tied into better fundamental research into establishing these links definitively and having good biomarkers to capture acute chronic disease and late chronic disease, right? Because it's probably a different profile of whatever systemic process is at play. And I don't know that we're there yet for a lot of these conditions. 

That's why you're doing this, right? Because there's so much awareness that needs to be raised and much more fundamental research that needs to happen. So, pie in the sky would be to understand more mechanistically what's happening with these diseases, and hopefully that leads to better treatments. But what those would be specifically, I don't even think I could hypothesize because the mechanisms are still not fully understood. 

Dr. David Putrino 
I mean, I'm a rehab person, so I feel like a lot of our success in rehab tends to come from understanding problems you can fix versus problems you can't fix, right? And not just putting your head down and saying, well, if the rehab isn't working, it's because you're not doing it right as the patient or whatever the case may be. It's really trying to understand, is this a rehab problem?  

So, I totally agree with where Amy's coming from and so, you know, so pie in the sky for me would be someone comes into our clinic, we take blood to understand what their immunological status is: “do they have T cell exhaustion? Are they expressing functional auto antibodies? Are they producing antibodies for all sorts of viruses and bacteria and so on and so forth. “ 

While you're taking blood, you take a bunch of tissue and you test that tissue for pathogens. Not for antibodies that your body is producing for the pathogens, the pathogens themselves: “Do you have Bartonella sitting in your tissue? Do you have EBV actually detectable and sitting in your tissue? Do you have SARS-CoV-2,” et cetera, et cetera.  

I think that this is a piece that has been missed and I think medical students need to hear it over and over again. Like, the things that we test for right now, if we're trying to understand if a pathogen is present, it's really superficial and it's in our blood and it's not really looking for evidence of the pathogen itself, it's looking for evidence that our body is responding to a pathogen, which doesn't really answer the question of if the pathogens there, it answers the question of, does your body think the pathogen is there?  

And the ground truth could be,: “yes, it does, your body thinks it's there, but it's not really there and that's a problem that needs to be solved with a whole class of other drugs”. Or “yes, it is, and that's a problem and now we need to solve that with a class of drugs that seeks out and destroys those pathogens”.  

  All of those issues can't be fixed by physical therapy or physiatry, right?  

So, you know, that's my like first screen is I want to know, are those pathogens present or is there an immune system that really, really thinks those pathogens are present and therefore no matter how much rehab I do, you've still got this immune dysregulation that's never going to go away or you've still got the system pathogens that are never going to go away.  

Once we've done away with that, you know, the next tier of things that I'd want to know, we need better outcome measures for everything. We haven't even nearly scratched the surface of measuring all the different levels and types of fatigue that people are experiencing, measuring all the different types of exertional intolerance that people have.  

So one of the things that I would want and this is something that we're actively working toward in our lab is continuous monitoring as people are going through rehab so we can capture heart rate variability, we can capture hormone levels, we can capture a bunch of metrics of health, you know, transcranial, Doppler, etc. There are all wearables that are emerging right now that can do that. Stat Health has created an earpiece that can measure blood flow to the brain. There are wearables that measure hormone levels from your sweat. Bit of a problem if you don't sweat so much with dysautonomia, but even still, they're somewhat sensitive, even in folks with dysautonomia. And then HRV is emerging as a very important metric for predicting symptom burden in people with dysautonomia and POTS.  

So my ability to sort of sit at a control panel and understand, “okay, this person's heading for a crash because of the way their hormones have dipped or because of the way their heart rate variability just moved, I should call them up. I should make sure that they're doing all of their mitigation strategies, that they're doubling down on pacing.” That level of precision medicine from the rehab side, once we've dealt with all of the things that rehab can't help with, would be game changing.  

And then I'm gonna hand it over to Shannon by saying, just like all of our rehab metrics are inadequate, all of our psych screens -- things like the GAD, which is a generalized anxiety disorder screen -- it's so inadequate for what we do. So many people can check that off and the feelings that they're experiencing could be coming from anything. And you can say, “Huh, we're seeing generalized anxiety here. You probably have a generalized anxiety disorder.” I'll hand over to Shannon because that's not my domain. 

Shannon Delaney 

Yeah, I would just echo everything that you're saying. And certainly looking and establishing a psychiatric diagnosis says nothing about the underlying root cause of those symptoms. I'll just speak a little bit to the tick-borne illness realm because that's kind of where I live, oftentimes. I would just say treating tick-borne illness is... like, these illnesses are incredibly stealthy and incredibly complicated and if I wasn't like living and breathing it every day and seeing the intensity of these symptoms in patients, I would never believe it. 

A big issue with the field and why it's so controversial is because, part of the reason is because, the diagnostic testing is just not there. So as David was explaining, most of the tests are indirect antibody tests which doesn't give you a lot of information other than to say, “Okay, it looks like your immune system was exposed to this particular pathogen in the past. We don't know, was it two months ago? Was it two years ago? Was it 20 years ago potentially?” So it doesn't tell us whether or not someone is experiencing an active infection. We really just have to piece together these antibody tests and then what their clinical symptoms look like at the moment.  

But if I really had a pie in the sky, I would have better diagnostic testing for active infection. And I'm glad he mentioned the tissue-based testing because I think there could be potential amazing progress in that domain because a lot of the tick-borne illnesses, they usually don't hang out in the bloodstream. They actually like to go into the tissues and that's kind of where they live and that's where they reside.  

A big problem with chronic symptoms related to tick-borne illnesses, anyway, is that there's a big debate in the field about what causes the symptoms. So, to what degree is it persistent infection? To what degree is it immune dysregulation or immune mediated symptoms that may or may not be related to an underlying infection? So if we had better methods to detect these infections -- and I personally think there's a lot of persistent infection that we just like can't detect, and it's probably a mix of both -- it's probably the persistent infection that's causing the immune dysregulation.  

I also think that in this realm, there's like very, very little to no treatment guidelines, partly because it's so controversial and a lot of the medical establishment hasn't recognized that this is actually, like, a thing. And so it makes it very difficult, not only for patients when they try to understand what's going on with them and what their treatment path is gonna look like, but it also makes it very difficult for physicians who are trying to treat these diseases. So, ideally, if we had research-informed treatment guidelines, that would be amazing progress in this field. 

Dr. Raven Baxter 

Thank you. Yes, I co-sign all of those recommendations. It's really good. So I wanna jump back to something that David mentioned. You heavily were leaning toward technology. I'd like to pick your brain and talk about how can technology assist the physician in their diagnostic practice? 

Dr. David Putrino 
One of the things that I would say in favor of technology is, you know, we've all seen the same sort of characterization of joint hypermobility disorders and post-acute infection syndromes and some of these other complex chronic illnesses. They're always called mysterious, they're always called all manner of things to kind of say like, “we don't really know if this patient is telling us the truth or not” is really what mysterious is code for, but what they actually are, if we're putting the blame in the right place is they're poorly characterized. You know, they have not been well characterized by medical science over the decades that people have been showing up saying, “I'm sick and I don't know why.”

Just like I said, I find it hard to find a physician who can explain to me with any level of detail, a difference between fatigue, exercise intolerance, and post-exertional malaise... three different states that present entirely differently, but usually a physician will just write down “patient complains of fatigue.” So technology gives us the ability to characterize what patients are feeling in their day-to-day life. That's what I get excited about. I get excited about the idea that we can use technology to understand what a patient's physiology is doing when they're at their worst and what a patient's physiology is doing when they're at their best. 
 

We very rarely see patients when they're at their worst. When they're at their worst, they're canceling appointments saying, I can't come in today. Most of our long COVID patients, if they're showing up in person -- and we have at our center a prodigious cancellation rate, you know, it's a problem we need to do something about -- but when they're coming in for an in-person assessment, that's a good day for them, you know? Very few patients when they're having a bad day can actually get on the subway, make it uptown, go through a tilt table test...are you kidding me? You know, that's very physiologically taxing. So the ability to have some sort of technology that is monitoring them day in and day out is, I think, crucial to understanding the illness.  

And then the other piece, as we go into characterizing these illnesses, I do have to go back to developing the technology for understanding whether or not persistent pathogens are present. I know it's a hot button topic. I know it is a controversial topic, but the reality of the literature is that we are finding pathogens present in people. We're finding it in the tissue, we're finding it in the gut, we're finding it in different body parts and we need to understand the significance of that. If we're going to have any hope of developing effective treatments that either address persistent pathogens or don't, we need to characterize what pathogens are present in each patient and understand the significance of them being present. Is it affecting their symptoms? Is it not?  

And the central dogma around, “oh, these tick-borne infections, we're not really sure if they're real or not.” It has been controversial. When you actually dig into the literature, it's not controversial at all. These are just opinions that certain folks in power are holding that are not based on what's published. What's published tells us that there's lots of species of tick and vector borne illnesses that persist in the body and we are slowly developing tests that can find these pathogens as well as others, as well as viruses and so on and so forth. 

The truest answer that actually is a good conclusion from the literature that we have is we would be crazy not to characterize all of these things, develop the tests that allow us to measure these things and understand the significance of them in the overall presentation of our patients. Until we can do that, you know, we're failing our patients. It seems very, very discouraging to me that we would try and force autonomic rehab down someone's throat for twelve months, when their real problem is something that requires antibiotics or antivirals to treat. 

So, technology that allows us to better characterize globally what's going on -- what organs are affected, what pathogens are in play, what immune dysregulation is in play, as well as micro day-to-day, “what does your day look like and how can we help there” -- that's where I see the role of technology and it's a crucial one. The reason these complex chronic illnesses haven't been figured out is because they're complicated and with the tools that we have we can't, so if we keep just trying to use the same tools, we're not going to get anywhere. 

Dr. Raven Baxter 

Thank you, David. I wanted to do something a little different on this episode. I wonder, would you all be down to do a role play of a hypothetical scenario with a complex patient? Would you be down for that?  

 

Dr. David Putrino
Sure.

Dr. Raven Baxter

Great. Okay, so I guess I would just take myself for an example. Let's pretend I am not healthy at this time. Take it back two years ago: I am bed bound and I had trouble getting in, but I got into the doctor's office and this is my complaint. I would like to know, because I feel as though I would land in any of your offices, I wanna hear what your response would be and how you'd approach this.  

So, I got COVID two months ago. I've lost all appetite and sense of thirst. My body forgot how to sleep. So I... I feel like my clock is off, my body clock is off. When I stand up, my heart is pounding like I just ran a marathon and it wears me out to walk to the bathroom, which is about 30 steps away. Um, let's see. I have panic attacks whenever I eat any food at all and whenever I drink anything. 

I also have panic attacks regularly throughout the day, but especially when I wake up, like immediately when I wake up, and usually one big one in the afternoon. But I don't have suicidal thoughts, and I was not formerly anxious or depressed, and I've never had panic attacks before. I'm losing muscle mass. I have not been able to eat anything for a little bit over a month now, so, uh, it's looking really slim. I also have tinnitus. So, what do I do? What's wrong with me? What do you do? 
 

Dr. David Putrino 
Are we allowed to be sort of ideal? Like this is the ideal care that I would provide you with or is it like what's pragmatic, what's real? 

Dr. Raven Baxter 
I think that we should do a role play of a realistic...like what a doctor today would have to decide with what's available right now and the knowledge we have right now and the tools. 

Dr. Amy Kontorovich 

I think it's a hard scenario to role play because we're coming -- I think I could speak for myself, but I have a feeling that Shannon and David would feel similarly -- like we're coming to this topic with a certain amount of experience where I think we would hone in on something specific here. But if you're asking what a typical encounter would be with a provider who maybe isn't as zoned in or honed in...um, yeah, I could role play that, but it might be insulting.  

Dr. Raven Baxter 
I think maybe you should. 

Dr. Amy Kontorovich 

Well, I don't know that it's, you know, necessarily useful, right? Like, what should we be doing? So you've said so many very key phrases that an AI model for dysautonomia would absolutely pull out and flag for dysautonomia. Maybe it's not the answer, but it's definitely high on the differential. So, I can't say that a general provider who doesn't think about this obsessively all the time would hone in on that the way it would. But an NLP and a MMI model would. 

Dr. David Putrino 
Yeah. I agree with Amy. I think that you've got a real biased group here, but to quickly answer your question, we'd want to put you through autonomic testing, table test and cardio vagal testing and pseudo motor testing and the works. You're experiencing heart palpitations. Prior to your COVID infection, you were healthy and didn't have any other diagnoses. So of course, we'd want to do an EKG and maybe an echo as well, depending on what Amy thinks. And if your sleep is significantly disrupted and we're not making any progress on these things like autonomic rehab and breath work and so on and so forth, we would want to do a sleep study and understand what's happening with your sleep. The other thing that we'd want to home in on, is you said panic attacks. Were they your words? Were they the first physician that you saw saying this is a panic attack? Can I ask that? 

Dr. Raven Baxter 
I mean, I wouldn't know how else to describe them other than like, just an irrational sense of impending doom. But not anxiety driven, just my body felt like it was in danger. 

Dr. David Putrino 

Hmm. And they were happening after you ate and after you woke up, which is a very autonomic nervous system thing to do to someone when it's not behaving itself. So, yeah, to Amy's point, I think that we're all probably pretty biased, but I think the points that are really important here from my perspective, that I think a lot of people miss that are really cut and dry, right, is we know that infections can cause chronic and long-term symptoms. So like the first thing that should go down on a piece of paper is you were perfectly healthy, you had an acute SARS-CoV-2 infection and now you're not healthy. 

You know, like, that’s the key point that is so often missed simply because probably at the same time your typical, GP or PCP is taking blood and saying, “well, your blood work is fine, your vitals are fine. So what else is going on in your life that could be causing these physical symptoms”, as opposed to honing in on the really big clue that you gave them, which is: “I had COVID two months ago.” So, I would say that probably in a typical medical encounter, the biggest dropped ball is completely disregarding an acute infection in the medical history. 

Dr. Amy Kontorovich 

Yeah, and two years ago when you were ill, it may have been something that you volunteered because it was on the front of mind for everyone, the top of mind for everyone...patients, providers. But in the current era when there's not as much sort of attention in the media on COVID and just in everyday life, we’re not living through like the height of the pandemic at this time, thankfully, it may not be something that you think to endorse so it's incumbent upon the physician to ask the right question. 

Dr. David Putrino 

And also just a tip of the cap and massive respect to Shannon and what Shannon needs to do, which is in kids, multiply that by a thousand because it's like, you know, I have this much experience with post-acute infection syndromes in kids at this point in my career and life. And our number one presenting symptom with kids with long COVID is an upset stomach. 
 

It's unusual for a kid to say, I am more fatigued than usual, right? Or when I go for a run, I crash hard afterwards. Or, gee, my cognition doesn't seem the same in school. Like these aren't things that are really picked up. The cognition part is sometimes picked up by teachers, but they often assign something else to it.  And so the number one presentation that came to us in our clinic with kids is that they’ve just had this persistent upset stomach for a really long time and then you start asking questions. And as you start asking questions, it's like, “oh, well, yeah, actually they do seem more tired than usual. And yeah, you know, they used run around with their friends outside. Now they're more into video games.”  

And you start checking off boxes and you're like, well, when did all this behavior change start? And it's like, “well, actually it was just after they got COVID” which was twelve months ago by the time they get to us.” So, Amy's so right. It's about asking. It's incumbent upon the clinician to ask the right questions as part of a full evaluation and that goes double, triple, quadruple when it's peds because it gets even harder. 

Dr. Raven Baxter 
Thank you David. Shannon? 

Shannon Delaney 
Yeah, I think they both did an excellent job of kind of hitting all the high points. I would just say that when I see a patient for the first time, I have the luxury of spending like two hours with them and like really getting into a thorough medical and psychiatric history and doing a ton of blood work and then meeting up with them in a couple of weeks when all the blood work is back.  I know that most doctors don't have that luxury, but it's a really important key piece of really understanding what's going on with the patient. 

Dr. Raven Baxter 

Yeah, absolutely. And I think asking the right questions, but then also being aware of the questions to ask or the things to pay attention to is really important. Like, for example, I cycled through many doctors who really didn't believe exactly what I was going through was linked to COVID. So like, for example, when I mentioned I was having the panic attacks, they wanted to send me to an eating disorder clinic instead of treating me for the actual root, which was the infection. So I had to do that and that was really not what was wrong with me. As David mentioned, it was more of a dysautonomia issue. I don't have an eating disorder. 
 

So yeah, I mean, the process of getting diagnosed with a post-acute infection syndrome can be traumatic for the patient and it is important to listen and ask the right questions and be aware of things that they are saying so that you don't send them into a situation that is potentially harmful or not even the right place for them to be in. So yeah, I can't emphasize that enough, how important this step in the process is.

Shannon Delaney 

I just want to point out one other thing. When David was mentioning that, upon hearing your story, I think the most logical path that someone should take is that you were completely normal until you got COVID infection and anybody, even a non-medical provider, could kind of home in on that.  

But I think for whatever reason, and I haven't completely figured it out, but I think a lot of physicians have a difficult time with uncertainty and the more complicated medicine gets, the more uncertainty there is and more unsettled science. I think doctors have a difficult time just saying, like, I don't know. Like, this is the most rational explanation for what's going on with you, but we just don't know why you're experiencing these symptoms.  

So, instead of sitting with their own discomfort of saying, I don't have an answer for you right now, they will then send you to go see a psychiatrist or an eating disorder specialist because that makes them feel a little bit better in the moment. It eases their uncertainty about what's going on. It doesn't help you of course, because it's like not putting you on the right path.  

But I do think that if we're really thinking about underlying psychological motivations or inclinations about why we see this behavior so prevalent, I think that's kind of at the heart of it. 

Dr. Amy Kontorovich 
Not only does it not help you, it actually harms you, right? Because the more you're being driven down the rabbit hole and exhausting your limited energy resources to undergo additional testing and go to doctor's appointments and, you know, pursue these questions, probably many patients will start researching online these various entities that they're being told they needed to be you know, evaluated for and ruled out for, that actually drives the anxiety further. So if there's an inherent set of symptoms that are coming from organic disease, if you layer on the iatrogenic impact, it actually drives more anxiety. 


 

Shannon Delaney 
Totally agree, 100%. 

Dr. David Putrino 
I also want to throw in one little pitch for, you know, you presented this case to three people who have seen a lot of complex chronic illness at this point, but I don't think any one of us would advocate for not following up on some of the symptoms that you're reporting if we felt the need, right?  So the other side, the dark side of it is we stop listening to you after we hear, well, it's two months out from my COVID infection. And then we're just like, oh, long COVID. It doesn't really matter what you say, we're putting you on the long COVID track.  

I think it's also important -- it's one in a thousand, it's one in 10,000 -- but we've seen it enough that it happens that these fit, healthy, thirty-something people come to us and they do have a heart issue that does need to be addressed. But it's presenting with “when I stand up or if I walk stairs, I get palpitations and I feel like I'm going to pass out”. Maybe the COVID triggered worsening of the cardiac condition to the point where it needed attention. Maybe it didn't. But the point is that it's a cardiac issue that needs to be addressed. You know, a good clinician also needs to know when to zoom in on some of the psychiatric symptoms that you're reporting and not just immediately say,” Well, your panic attacks are from dysautonomia and they're gonna be fine once we address the dysautonomia”.  

It's like actually taking the time to sit with you and clear that it makes sense that it's from the dysautonomia, but let's really just have a bit of a chat about it and make sure that it's not coming from somewhere else because we still do need to do the diligence. I don't wanna say that we weren't saying that because Shannon was like, hey, two hours, right? Which yes, diligence is important. 

And ultimately, a lot of this can be traced back to a PCP has only fifteen minutes with you. And they're just gonna jump on the most obvious thing that they can refer out to like a life raft. They're gonna be like, “oh, panic attacks while you're eating? You know, that seems like something I can work with in 15 minutes. Let's send you to an eating disorder clinic” because that's what they have time for. So, you know, let me put in the plug for giving physicians more time with their patients and getting insurance to pay for it. 

Dr. Raven Baxter 
Yes, and this kind of leads me to a hard question that, I mean, a question that I think would be hard for you all to answer, but I think that you can do it. So what do you do when you don't know what to do? Like, if the diagnosis is not clear, if within the fifteen minutes, you can't make much of anything make sense, and the appointment is over, what do you do? Because these illnesses are very complex and more likely than not, this may be the situation that the medical students will be in. I'll give you some time to think about it. 

Dr. David Putrino 
I refer to Shannon. No, but for real, but for real...refer out, right? So there's always something you can do, you know, and sometimes that something is finding someone who's more expert than you. You know, no matter how challenging the patient, no matter how complex the patient, you always have a hunch of what you think are causing the symptoms, right?  

And so then at that point, when I'm at a dead end, I'm like, well, who's the most knowledgeable person I know in this direction of what I really think my best gut feel is causing the symptoms. Let's get them to that person. And even if I don't have that sense, if I'm just like, “I have no idea what's going on here”, I've got like four or five people on my list who are just like, these are the people that if I really don't know what's going on, maybe they've seen something, maybe they've done something, you know, that I don't know about and I refer out.  

But I think again, it all stems from tackling -- and this is the thing that medical students need to hear, -- tackling that uncertainty and tolerance head on and being able to say, “I don't know what is happening with you, and I'm gonna refer you to a friend, and I'm gonna do the necessary follow-up to make sure that person takes your call and takes your email, schedules an appointment with you”. That is the best thing you can do at that point when you're at a dead end, is have the vulnerability to say, “I don't know what's happening, but let me work with someone who will figure it out”. And honestly, those are the most heartfelt thank yous I've ever gotten from patients. It has never been the people who come in and you're like, I know what's happening here and you fix something bing, bang, boom. Like, yeah, you get a nice thank you and sometimes even a hug, but it's like, that's it. The best thank yous are when you fail utterly, but you're like, “I know someone who's not me, who I think can help”. And then that person can help. So when I'm stuck, I just refer and I tell them straight up, “I don't know what's happening here. I'm out of ideas, but let's find some more ideas and fresh eyes.” 

Dr. Amy Kontorovich 
I think more providers need to be able to say, “I don't know.” I really like what you said Shannon. It's much more helpful. As I've said earlier, as I've seen in patients who ultimately end up with a diagnosis of EDS or dysautonomia or both, but who have been on a several-year diagnostic journey, it's being told that you have something definitively based on no objective evidence to that case, that creates more challenges to engaging with the care that's needed for the correct diagnosis. So if more doctors could just say, “I don't know”, I think it would do a great service to patients.  

But to answer your question about what I do, I was trained in a field that is very dependent on diagnostic testing. Cardiologists are enamored with diagnostic testing because we have really great diagnostic tools, but they are great at diagnosing people with conventional straightforward disease and not complex disease that is test elusive based on the tools that currently exist. So I had to learn how to be comfortable with uncertainty. 

One of the techniques that I've developed in these cases is to think about: “what is the most neutral thing that I could do for the patient or recommend that could be both a potential therapeutic avenue and also potentially could inform on the diagnosis”. So for example, if we think that someone hasdysautonomia, maybe it's worth doing some formal diagnostic testing, but maybe the first thing we would do is do a trial of autonomic interventions that may demonstrate, you know, the patient may demonstrate improvement and that in and of itself is both therapeutic and diagnostic. So that's just one example. 

Shannon Delaney 

Yeah, I would just add that I totally echo what they're both saying. I think referring out, consulting with colleagues, I think a team-based approach is definitely the best way to go. Oftentimes when I see patients as the specialist involved, I try to reach out to their primary care doctor or their pediatrician. Sometimes it goes really well, but sometimes honestly it doesn't go that well because this is like such a new science.  

Just a couple of days ago, I reached out to the pediatrician of a seventeen-year-old girl who has a diagnosis of both Lyme disease and Bartonella. The pediatrician had been treating her for a few years and did like all the standard tests where everything was negative. And so he basically said, okay, this is all like psychiatric and referred her to the psychiatrist. She was put on a bunch of psych meds. None of them helped.  
 

Meanwhile, this girl can't even walk without holding onto a wall because she's so dizzy and she has gait instability and the pediatrician is still saying that this is all psychiatric and all psychological. So I was on the phone with him having a conversation about the positive blood tests and how I really thought and felt that it warranted additional medical, more aggressive medical treatment.  And he just was like not a believer at all and said she had a brain MRI that was normal. It got to be quite heated, because he said, “I've been practicing in this field for 50 years. This is not what this is”. 

And so it got to the point where I was almost ready to just get off the call, because it was such a difficult encounter overall, and it's like, you can't change someone's mind. But then there was a little bit of a common ground. He said, so how about we do additional testing. And together, we kind of decided what would be best. We agreed on a SPECT scan, which can really like judge how her brain is metabolizing things. And usually SPECT scans in this setting are always abnormal. So that was kind of the common ground that we that we found in discussing this very complicated patient. So even though it wasn't comfortable from my perspective, and it would have been a lot easier not to reach out to them and have the discussion, I do hope and think that this patient will be better served as we get together. That people who don't necessarily agree on it will come to a better diagnosis and treatment plan for this particular patient. 

Dr. Raven Baxter 
Wow. Thank you everyone for your insights. As we conclude today's enlightening discussion on the multifaceted approach to diagnosing and treating post-acute infection syndromes, it's clear that the path to recovery requires a collaborative and patient-centered mindset. Our guests, doctors David Putrino, Amy Kontorovich and Shannon Delaney have shared valuable insights that not only highlight the complexity of these conditions, but also the hope and potential for innovative treatments through interdisciplinary collaboration. So we hope that this episode illuminated the importance of diverse health strategies to support those navigating the long-term effects of post-acute infection syndromes. Thank you for joining us, and we look forward to exploring more topics with you in future episodes!