Chris Casey
First of all, could you tell us how did you get interested in infectious disease as a specialty to begin with?
Kristine Erlandson
So I would say I was probably interested in infectious disease starting in high school. I read some of those books on the hot zone and Ebola outbreaks and HIV was really an emerging outbreak at the time as well and continued that interest through college. Started to see some of the public health impact of infectious disease on a much wider scale and then was really interested in infectious disease throughout medical school, despite people telling me many times that, oh, you'll change your mind. I kept an unwavering interest in infectious disease and continue in that field today.
Chris Casey
Nice. And then how did you become interested in long COVID as an area of research?
Kristine Erlandson
My research within infectious disease is focused on long-term complications of HIV infection. We look a lot at physical function, comorbidities, things that develop as a consequence of either HIV itself or of the treatments for HIV. And so it really overlapped incredibly with COVID and in the same way I think we see a lot of similarities between people at the beginning of COVID and all the uncertainties. We don't know what to use to treat, we don't know how to diagnose, and a lot of that was the same experience that many of our patients with HIV had early in the HIV epidemic.
Chris Casey
Thank you.
Thomas Flaig
So it's Tom Flaig here. Really glad to join this conversation. So Kristine, thinking back to the pandemic, I remember in the midst of it, in fact we interacted in different ways as you were doing this great work. It became an awareness of long COVID, I guess we're calling it now, and in the emergent of this certain clinical entity. Then the clinic emerged, right? It's one of the only clinics – long COVID clinics – in the region. I know you've been very busy and I've watched your progress. Can you tell us a bit about what went into the emergency clinic and how that came about?
Kristine Erlandson
First, just a disclaimer that I don't see patients in the long COVID clinic, but I've watched my colleagues grow this clinic tremendously over the last few years. The clinic actually started as a post-ICU syndrome clinic, and a lot of these symptoms patients had developed for years before just as complications of being in the ICU for a prolonged period of time. They might have weakness or confusion from being on a ventilator, just even post-traumatic stress from being in the hospital for that long and going through such a tremendous illness. And so I think the long COVID was something that initially when patients were so sick with COVID, this was a clear transition from what we saw from typical post-ICU syndrome.
And the clinic was already set up as a multidisciplinary clinic with neurologists and physical therapists and other subspecialties that could help with some of the complications of a prolonged hospital stay. It just nicely transitioned into a long COVID clinic. Clearly, it's grown tremendously. It started as a very small clinic that Dr. Jolley had followed some patients and has rapidly expanded to see I think now over 2,000 people in the course of the last couple of years. So, it’s a huge, growing clinic.
Thomas Flaig
Yeah, I was just going to ask you some more about the status of that clinic. So it's a lot of patients, a couple thousand patients. And how often are patients seen in that clinic, how does that function for them, and are more patients being referred in or is it something now we see maybe a decline in usage of or the need for such a clinic?
Kristine Erlandson
It's definitely still a need. I think there's a lot of people that are impacted by long COVID that have been overwhelming primary care, or primary care providers in the area feel like they can address some of the symptoms but really want to reach out to specialists to see if there's other things they can be doing to help their patients. The clinic has continued to grow, they continue to see lots of referrals. They try to do some visits with a multidisciplinary approach, so a patient might come in and see pulmonary critical care doctor, they might get pulmonary function testing, an evaluation by a rehab doctor and get all of these in one place. I think a lot of patients with COVID have a lot of fatigue and it's really hard for them to come out to a visit and so the idea of going and having five visits to get something accomplished is really difficult.
So having a one-stop shop where they can come and get a lot of different workup in one time and hopefully get some answers has been helpful. They've recently rolled out a lot more telehealth too, so they might see a patient initially in clinic and then follow up via telehealth and this is clearly a statewide issue. So that's been really important to be able to allow outreach and have patients from all over the state of Colorado come in for evaluation.
Thomas Flaig
I'm glad you mentioned telehealth. It's one of the things that really emerged out of the pandemic, and I think for a lot of us it's been one of the larger changes in medicine that does seem to have some staying power. I guess in this situation, with the symptoms of fatigue that patients are having, it seems like a great option for them.
Kristine Erlandson
There's certainly some things that still require an in-person visit, if somebody needs a CAT scan or an MRI or some sort of imaging or an initial assessment with a rehab physician, they might need to come in person for some of that. But I think a lot of it really has been successfully rolled out with telehealth.
Thomas Flaig
Well, let's segue to some of the research that you've been doing including some recent publications. I think it is really exciting. So the National Institutes of Health has dedicated funding to what we're calling the RECOVER initiative that you've been involved with and you're part of the team that recently published this work. So what questions were fundamentally tried to answer with this endeavor?
Kristine Erlandson
So the RECOVER study is unique from a lot of other studies in that it is enrolling patients prospectively, so not just people who had had COVID and going back and looking in the electronic health record, but catching patients at the time of COVID who have previously had COVID and have had long-term symptoms as well as a group of people who have never had COVID before. And so the study really sought to compare COVID symptoms or symptoms that we have attributed to COVID across these different groups. They teased out symptoms that were much more common in people that had had COVID, not necessarily more common in general. A lot of people may have shortness of breath or fatigue in general, but they tried to pick up those symptoms that were really unique to previously having COVID to come up with more of a research definition that we can use for COVID moving forward, which has really been a limiting step in research – not having a clear definition of these symptoms.
Thomas Flaig
So one of the main goals of this was really to define the syndrome or the constitution of symptoms around this. So what was that major finding? Is that research definition easy to summarize or is it pretty complicated?
Kristine Erlandson
They had a scoring system and there were several symptoms that went into this symptom score that were more common in people who had had COVID. Some of them are things that we all think of like the loss of smell or taste that were clearly different in people that have had COVID. Some are common like gastrointestinal problems or fatigue and then there are a lot of symptoms that were reported overall. It was just trying to tease out these symptoms that were really different in those two groups. I do think it's important to mention that this is currently a research definition. I think there was a lot of concern initially that this would define people who had COVID and those who needed care for COVID might not get it because they maybe didn't meet some of these criteria. It's not a clinical diagnosis at this point. There may be things that get added to make it a better diagnosis or something that we could use in the clinical setting, but it's not ready for clinical use at this time.
Thomas Flaig
So you had these symptoms that were specific or that define the entity. There's also this word ‘long’ that's been used around it. So what do we know about duration and has this study helped us understand that?
Kristine Erlandson
There are certainly a lot of symptoms that can happen after COVID and many of them will resolve within a month or two after COVID and probably don't reach into that long COVID definition. I think when we're thinking of long COVID we’re thinking of symptoms that continue for three or more months and some of them can continue for years, as we've seen from some people that were impacted from COVID in the first wave, but some may resolve within six months. And we're trying to find those that do continue to cause a lot of disability and a lot of impairment for people so we can target those in terms of treatments.
Thomas Flaig
Did the study look at certain populations and could they find certain populations or characteristics that put people at risk for developing long COVID?
Kristine Erlandson
There’ve been several studies that have come out over the last couple of years really looking at the high-risk patients for developing long COVID. There are risk factors such as age. There's a bit of a debate about some populations that seem to be at risk for long COVID. Women in particular had much higher rates of long COVID in the literature, but there's some question about whether women may seek out care more or may be more vocal, may better reflect their symptoms that they're having or see their primary care providers more and ask for a referral. There are also studies that get into the biology of that, and there may be things related to estrogen or other factors that actually do increase long COVID symptoms in women.
We know that people who had more severe COVID probably have more long COVID symptoms. Certain comorbidities like obesity or diabetes are probably risk factors and then having vaccination for COVID probably protects against having long COVID. Several bouts of COVID also seemed to increase the risk of having long COVID. So if someone had COVID five times they are probably at higher risk of developing long COVID than someone that had it once. And then whether or not it's a vaccination effect or other effects, we do see there's probably a lot more long COVID or more severe long COVID with that first bout. And you still hear from people that had COVID back in March of 2020 and how it still had a major impact on their ability to function.
Thomas Flaig
Are some variants more associated with long COVID than other variants?
Kristine Erlandson
It gets a little hard to tease out because of the issue of vaccination and that we've had more and more vaccination over time and people have had some immunity to COVID because they may have had it before. There probably are some of the earlier variants that seem to be associated with a greater risk of long COVID.
Chris Casey
Kristine, are there any attributes that our campus has that enabled your study to be as productive as it was in terms of getting data such as a uniform method of questionnaires to patients or maybe electronic health record databases? Was there just certain attributes that were available that made the study more conducive here?
Kristine Erlandson
Probably the biggest factor for us was the clinical translational research center and just having that facility where we could study participants and get all of their visit done in one place. So our participants can come in, do their consent at that visit, get a blood draw at that visit, oftentimes get some of the other study procedures that may go along with that, like a liver ultrasound, echocardiogram, different imaging. So just having that one place they could go really helped quite a bit with visits. We have a great electronic health record team here and we've been working with them to be able to access positive test results so that we can prospectively reach out to people who have had a COVID diagnosis and offer them participation in this study.
And then our pharmacy team was actually great about helping us to put information in some of the prescriptions for acute COVID or some of the monoclonal antibodies and trying to reach out to people who had COVID at the time. So there's a team in the emergency room that was doing a lot of screening for COVID trials at the time. And they were also great about if someone didn't qualify for one of their studies, which were pretty time intensive, then they would refer them to us to potentially participate if they were interested. So definitely.
Chris Casey
Those living with COVID, what are some of the long-term expectations for them going forward at this point? Is there, I know it affects everybody differently, but is there any uniformity on what the expectations of duration and just severity of long COVID could be for them?
Kristine Erlandson
I think it depends a lot on what their initial symptoms are. Some symptoms seem to resolve faster. Some symptoms seem to be particularly disabling in some patients and they may have symptoms for two or three, almost going on three years now, that they're still impacted by the symptoms. There are some therapies which have seemed like they've helped for certain symptoms like patients that have had a lot of exercise intolerance and fatigue. Our rehab team here has developed some guidelines on kind of slow return to exercise where it's just very small bouts of exercise with stepped rehab and they have developed some of the national guidelines to help with that slow recovery and helping patients get back gradually. Our cardiology team has been trialing some different treatments to try to help with one of the symptoms we have called POTS where people will have a lot of dizziness and lightheadedness after COVID, and they've been helping with simple things like using compression stockings and making sure people are getting enough fluids and salts and seeing how that can help.
I think encouragement has been helpful. A lot of it is just recognition, and I think patients sometimes feel like they're being ignored or not acknowledged that they have real symptoms and helping to go through that list of symptoms, understand what patients are really having or experiencing, and then developing specific treatments to treat those specific symptoms – even if it's not like a cure for long COVID. It's what can we help you with and how can we get you feeling better and back to functioning where you were before COVID. And then there's certainly trials that are rolling out. We've seen smaller clinical trials around the country, and we're excited that we'll be able to participate in some of the RECOVER clinical trials that we'll be starting within the next month or so.
Thomas Flaig
And maybe just a word about that. What's the patient population for the RECOVER treatment trials, I guess we'd say?
Kristine Erlandson
So they're rolling them out similarly to how we've seen some of the other COVID studies where it's a platform design and so kind of have a protocol that applies to all of the studies and then as participants come in and meet certain symptom clusters so they can be eligible for different study interventions. We're looking for patients that have fatigue and kind of exercise intolerance and patients that have more neurocognitive dysfunction and then some that have this autonomic dysfunction with the low blood pressure, poor heart rate response to exercise. And so if people meet different criteria in those clusters and different severity, so we want people that have pretty severe symptoms, then they can be eligible for several of those clinical trials.
The first one that we'll roll out is an antiviral treatment and then some of the subsequent ones look at low doses of exercise, cognitive training. There's some that are drug related or medication related, some that are more focused on rehabilitation. So we've seen them slowly roll out. We know a couple of them that we'll get to be a part of and we're hoping that we'll be able to be a site for these other treatments to really get them tested and know if they're effective or not. Similar to what we saw early in COVID, we don't want to see a small study and assume it's effective and use it for everyone. So it's great to be able to test this in a large randomized clinical trial setting with over 2,000 patients.
Thomas Flaig
And is there some place that people can go to learn more information about those studies?
Kristine Erlandson
Yeah, our RECOVER websites or RECOVER email. It's just recover@cuanschutz.edu. Participants or people who are interested in participating in the clinical trials can send an email to that and we can reach out with further information once we're ready to start enrolling.
Chris Casey
As I mentioned earlier that Admiral Levine will be visiting our campus this summer. Could you explain why she'll be coming and what will happen?
Kristine Erlandson
Yeah, we're very excited to welcome the admiral to the campus. I think there's probably a few reasons. One is we are a site for the RECOVER study. Colorado has really been at the forefront of rolling out clinical care in this multidisciplinary COVID response and there's been a large statewide effort to try to coordinate long COVID care across the state. I think the governor's office has been particularly interested in how long COVID is impacting our state.
There's been a push to roll out kind of what we think of as telemedicine, but education with the ECHO program or Project ECHO and trying to roll out education for providers across the state and making COVID care and COVID education more reachable to people who may not or to some of the providers that may not treat a lot of long COVID patients. We've also been one of the sites, particularly through our colleagues at Denver Health, to enroll more Hispanic participants than many of the other sites for the RECOVER study. So I think there's probably an interest in part because of our ability to enroll Hispanic and rural populations and other underserved populations that may not have been enrolled as much at some of the other sites.
Chris Casey
The admiral has been quoted in previous interviews saying that with regard to long COVID, we need treatments yesterday. So there's a real urgency, obviously. And when she references treatments, what sort of treatments are we talking about? You mentioned rehabilitation therapies. Does this go into antivirals and even mental health?
Kristine Erlandson
Yeah, I think so much of it depends on the more we learn about what's causing long COVID, and there's probably a lot of different presentations of long COVID. People who have long COVID that's primarily impacting their brain may have different things that are causing that. There may be an ongoing virus in their spinal fluid that's impacting their brain and we might treat that differently with maybe an antiviral or an anti-inflammation medicine. People who have exercise fatigue or difficulty with exercise, we might need to treat them with other medications, or other treatments like exercise. People who have a lot of fatigue sometimes might need cognitive training or different types of mental health interventions.
So I think that encompasses a huge amount of different interventions and it really is very patient dependent on what their symptoms are, what they've tried, what they respond to. And it may require a much more nuanced approach to treatment than here's the magic pill that treats long COVID. I think unfortunately we probably won't have that magic pill, but it's trying to figure out what symptoms each person has and what we can give them to help best manage their symptoms and help them get back to their prior level of function.
Thomas Flaig
There's so many questions that sort of swirl around this issue right now. I mean one that I've been asked a couple of times, even by a patient recently, was this idea of long COVID, right? And they described their experience with a neighbor or family member. Their question was basically, does this happen with all viruses and we're just focused on COVID so we know that. Is there something different about this particular one? I had the flu, something along those lines. So is this something pretty specific to COVID that we can tell?
Kristine Erlandson
There's probably some aspects that are more specific to COVID, but I think just the sheer number of people that were impacted by COVID led this much more to our recognition. In fact, delving back in the literature to give a talk a few months ago, I didn't realize there was a post-Ebola syndrome, that people had very similar symptoms after Ebola. We feel so distant from Ebola in our country that we don't appreciate some of these post-Ebola symptoms that people had. We see post-Lyme, I mean it’s a bacteria instead of a virus, but we do see some symptoms after Lyme disease that aren't really explainable and it doesn't seem to improve with ongoing antibiotics. So what's causing post-Lyme? There are certainly thoughts about EBV or Epstein-Barr virus –what we think of as mono – and whether that could cause ongoing symptoms.
So I think we definitely have seen it with other viruses. It's just the sheer number of people that were impacted with COVID and how common this seemed to be, especially initially, that we see this impact. I think as I mentioned earlier, there's also this post-ICU syndrome and I think that really complicated the initial long COVID and that we see not only people have this potential long COVID effect from the virus, but they also have all these ICU syndromes and ICU effects from just having this devastating infection where they may have been on the ventilator for several weeks, they may have gotten certain anti-inflammatory agents that cause muscle damage. They may have had this post-traumatic stress, all the social isolation that went with that. So I think that also complicated it and probably led to much higher numbers, particularly in the first wave of COVID.
Thomas Flaig
I think one of those other questions out there, you're thinking of providers, right, as an idea, as an infectious disease specialist, you deal with this and so forth, but there are other specialists that are going to touch on this and have patients they're caring for, maybe a different problem and this is part of it. Any ideas on how we educate, give the key messages out to the broader medical healthcare community?
Kristine Erlandson
I think the ECHO will hopefully help to roll out some of this education. I think podcasts like this can hopefully help and make this a more recognized condition. Patients should bring it up. I mean, if a patient had COVID and they think these symptoms for me started right after COVID, I mean it's definitely worth bringing up to their provider. And I also think from the same standpoint, we don't want to brush off symptoms as long COVID. We've seen people through our study who had ongoing fatigue and shortness of breath and they end up getting an echocardiogram or study of their heart as part of the study and we find something abnormal there that probably isn't completely unrelated to COVID, but we just happened to find it because of these symptoms. So I think it's still very important for providers to continue to look for other causes of symptoms and make sure that we're not missing treatable causes of other things that could be causing symptoms that we're attributing to long (COVID).
Thomas Flaig
Yeah. One question too is when you think of people that had mild or moderate COVID that developed long COVID versus those that are severe maybe in the ICU or something, any sense of that proportion of maybe those with milder symptoms that develop long COVID?
Kristine Erlandson
It's been strange. I mean we definitely see that people who had more severe COVID tend to develop long COVID, but there's many cases of long COVID in people who didn't even know they had COVID or who had extremely mild cases of long COVID. Overall, it seems to be that probably between 10 to 30% of the population experiences some long COVID. Those rates are probably much higher in those that were much sicker initially. But we do probably still see it in about 10% of people that didn't have very severe COVID at all. So I think it does still remain a risk and certainly keeping up to date with vaccinations and other COVID prevention remains important as much as we would like to just forget the whole pandemic.
Thomas Flaig
It's interesting to hear your motivation to go into infectious disease. From a young age, you were fascinated by the impact that infectious disease can have on people. So one question I would have for you, as an infectious disease specialist who's just gone through this pandemic, how has it changed your professional life or maybe your view of your career?
Kristine Erlandson
Yeah, that's really interesting. I think one of the reasons I went into or that I really enjoyed infectious disease once I got further along in my career trajectory was that we can treat people. So many different subspecialties, you can't really cure people. And a lot of the patients that we see minus my patients with HIV, that we've yet to find a cure, we can treat their condition and get them better. And I think that's what's been most frustrating about long COVID is we really haven't been able to make everybody better yet. But I think in general, it just reinforces the need for infectious disease and how valuable the specialty is, how necessary it is when things like pandemics come up and how we were, our field as a whole, was really able to reach out and lead some of the first vaccine trials, help with infection prevention in the hospital, all the important things that come with managing a pandemic.
Thomas Flaig
It sounds like you've even more inspired now than before having gone through this.
Kristine Erlandson
Yes.
Thomas Flaig
One more question too, and maybe this just a simple one, but so if there's someone listening to this who's dealing with long COVID, do you have kind of a simple message to patients that are dealing with long COVID with what you understand now and the research that's being done?
Kristine Erlandson
Yeah, I think the first thing is just that to let patients know that they're heard, that this is real. We understand it's real. We absolutely acknowledge that the things that they're going through are legitimate and long COVID is a real issue
And then I think with a lot of these chronic conditions, it's a multidisciplinary approach or a multi-pronged approach. For example, therapy, physical therapy or even psychotherapy or counseling may not seem like it's going to cure everything, but it's one part of an approach. And it may help in addition to medications or in addition to other treatments. So just being willing to try different treatments that hopefully can help as the providers work with patients to get their symptoms to hopefully abate and be able to return back to normal.
Chris Casey
Well, it's been a fascinating discussion, Kristine, and it's ever evolving, obviously. So thank you for the work you're doing.
Thomas Flaig
Thanks for all your work.
Chris Casey
And thank you for breaking it down for us.
Kristine Erlandson
Thank you for the opportunity to share and to put more word out there about long COVID.
December 5, 2023