Good morning, everyone. Welcome to session 1082. This is interstitial lung disease after surviving COVID-19. For those of you who were at CHESS 2022, we presented this topic then, and a year has passed, and so we're going to provide everyone what has changed between last year and this year, so we can remain up to speed with what's happening with these patients after they survive COVID. I'm Corey Kershaw. I'm at UT Southwestern Medical Center in Dallas. These are my disclosures, and so I'm going to be talking to you this morning first about the incidence and risk factors for developing post-COVID-19 related interstitial lung disease. These are some of our learning objectives here. We'll talk about the different types of ILAs you see on CT scan, what the risk is for patients who, after they survive COVID-19, for getting these abnormalities, and then what's the likelihood that they may persist in the months after the patient leaves the hospital. So just so we can have a common language, this is the WHO COVID-19 clinical progression scale, so if you're reading the literature about patients after surviving COVID-19, most of the time the authors will describe their patients using this scale. These are WHO class four through five patients, and so that informs us that these are patients who are hospitalized, required either no oxygen or a little bit of oxygen. They didn't need any more advanced therapies. Anyone who needs an advanced therapy, whether it is high-flow nasal cannula, BiPAP, mechanical ventilation, ECMO, those are all severe patients. So again, just so we understand when we're reading these papers what the patient population is. So I have a case. This is a patient from a few years ago. He came to my clinic at age 74 with absolutely no prior pulmonary history before he was infected with COVID. He was hospitalized one month before I saw him. He was in the hospital for about a week, eight days. He had moderate COVID, so he was hospitalized, had a low-flow oxygen requirement, but did not have to go to the ICU. When he was discharged, he still required oxygen after eight days, three liters, but was able to titrate off in the week or so after he left the hospital with the work of his primary care physician. He had some past medical history that might be relevant. He has a history of prostate cancer, was not or ever immunosuppressed for it, sleep apnea but not wearing CPAP by his choice, acid reflux, and hypertension. No past smoking history, and his BMI was 33. Here are some representative slides from the scan when I first saw him, which again was 30 days after he left the hospital. And I'll point out, let me see. Yes, there we go. So just a few salient abnormalities to keep in mind here. Where's my point? There we go. So he has some reticulations. You can see these extra lines here. He has a few areas of ground glass opacification, a little bit here, some right there. And then he has a few of these, you know, what we can just really best describe as lines, irregular lines, line here, line here, a few little extra lines here. You know, this is not blood vessel. It's just an extra line. These ILAs have been described in multiple papers. So once again, we can know what to look for. We can see ground glass opacities. We can see ground glass opacities with interlobular septal thickening. We can see these irregular lines that I was talking about before. Here's some examples of that. This patient has more than that, but these are the lines we're talking about. Consolidation, reticulations, and then a combination of things. This patient has a little bit of everything. He's got some consolidation, has some lines, some reticulations, and that's a pretty common scenario that we see. Other findings that have been reported, this is one paper from a Swiss cohort looking at patients in their institution that were hospital, that were seen four months after COVID. They saw a lot of mosaicism, a lot of hypoattenuation, much more frequent than you've seen in other cohorts. And most of their patients were severe. So don't be alarmed if you have a patient you see after surviving COVID, especially if they had severe disease where, in addition to some of the usual abnormalities I described, they also had these large areas of mosaicism because that has also been described in COVID survivors. So what about these patients? How common is this? So I'm going to talk about this in short-term and also long-term follow-up. So this is data from China very shortly after the beginning of the pandemic, early 2020. They looked at three hospitals in the Henan province of China, 55 patients all three months after hospital discharge. Most of them had moderate disease. So again, hospitalized either did not require oxygen or a little bit of oxygen. And they saw that 71% of those patients three months after surviving moderate COVID still had abnormalities on discharge. The most common things, and this tends to hold true from most studies you read, ground glass opacities, irregular lines. Those are really the two things that pop up most frequently. Here's a long-term follow-up study from Wuhan. Over 1,700 patients, again, early 2020. And they looked at patients six months after hospital discharge. Mostly moderate patients, scale three and four, but a little bit of, but then all, it was either, excuse me, either patients who had scale three or four or all their patients in their cohort with class five. They were invited to have an HRCT after surviving COVID. So every patient that left their hospital with stage, with class five, or some of the patients class three and four had CT scans. Over 50% of those patients still had abnormal CT scans six months after discharge. So if you take into account that they looked at CT scans in every patient that left their hospital that were in class five or above, over 50% of them still had abnormalities six months later. You'll see a trend here. The more severe the disease you see in the hospital, the more likely it is that they're going to have residual abnormalities after they leave the hospital. And that was their most common finding, that the likelihood of persistent, at least fibrotic-type ILAs, this would be either reticulations or some of those irregular lines we talked about, increased with the severity of disease. Another study from Belgium. This is, again, early 2020. At baseline, they had 234 patients that had a chest CT, and then they did follow-ups at either three months and then at a year. A lot of the patients fell out for the one-year CT scan, because if they were normal at three months, they did not get a one-year CT scan. They reported a prevalence of post-COVID fibrosis, so again, reticulations, irregular lines, of 10.4%. So, once again, they found that the more severe the disease, you can see, the more likely it was that they had at least fibrotic changes later on. Who's at greatest risk? Well, we've already sort of established, I think, that the patients who have more severe disease, those are the ones that are going to be at greatest risk of having persistent CT scan changes, even up to a year after surviving COVID. But some other things have been borne out. Hypertension, in this three-study meta-analysis from China, all their patients that had hypertension were more likely to have fibrosis on their CT scan later on. They also found that if they were in the hospital longer, that was a risk factor. And having increased inflammatory markers at the time of admission, this is certainly something that most of us were doing as soon as patients hit the door. They were getting CRPs and SED rates and a bunch of other things in order to help us guide how sick these patients were. Here's another meta-analysis pulled from 18 studies. And they included studies that were at least 50% of the patients in the study had severe COVID. So again, severe, more respiratory support in the ICU, BIPAP, mechanical ventilation, ECMO. And the patients in the studies that had more than 50% severe patients, the likelihood that pulmonary fibrosis was more was in those studies. So the more severe the patients, the more likely are they're going to have fibrosis. They did a meta-aggression, meta-regression analysis and also showed that being older and having a smoking history were risk factors as well. This is the Belgium study I showed earlier. They saw that disease severity, older age, longer hospital stay also. So again, the common theme. The longer the patients in the hospital, the sicker they are, the more likely are they are going to have fibrotic changes on their TC scan up to a year after discharge. This is some newer data that was just published this year from the UK ILD post-COVID-19 study. This is in the Blue Journal just earlier in 2023. And what they did is they estimated the prevalence of residual lung abnormalities in people that were hospitalized with COVID-19. And then they stratified them based on risk criteria. These were all patients that were getting scans within eight months of hospital discharge. Their cohort was pretty big, 3,700 patients. But only 209 of those patients had linked CT scans that were able to be reviewed with appropriate inter-rater agreement. And of those 209 patients, 166 still had persistent ILAs. And this is, again, they defined interstitial lung abnormalities in this cohort as more than 10% of the CT scan having ground glass opacities or particulations or a combination of those things that reached 10% of the scan. By doing some statistical analysis of their CT scan cohort and applying it to the larger cohort, they identified risk factors of having an abnormal chest X-ray after leaving the hospital, having a diffusion capacity less than 80%, or, again, severe disease requiring mechanical ventilation. And the more risk factors you had, two or even three risk factors, the likelihood it was even greater. Using that analysis in the small CT group and applying it to the larger cohort, they had an estimated prevalence of ILAs after COVID-19 hospitalization of 11.67%. So we saw that earlier study was about 10%. This study is about 11%. And then what's nice about this, as you can see, they did an estimation of the percent lung involvement the further along weeks after discharge. You can see it goes down, both for ground glass opacities and reticulations or that combination group of more than 10% of having a little bit of everything. So how does this apply to my patient? Well, he was a bit older. He was 74. He was hospitalized not for very long, only eight days. One of those studies in the Chinese meta-analysis, their length of stay was up to 19 days. He had moderate COVID. So he was hospitalized, had oxygen with a typical flow, but didn't require ICU level of care. Discharge on oxygen, as we said, but then off of it within a week. His past medical history includes hypertension. We saw, at least again in that three-study Chinese cohort, that hypertension was a risk factor. He had no smoking history, which was good. And as we can see, this is a scan on the right, six months after I first saw the patient, and his scan has improved significantly. And this is with no intervention at all. This is just with me watching him, bringing him back in six months, and seeing how he looked. And his CT scan is almost normal at six months. So it has a few residual reticulations, some lines, but a lot of improvement. So the message here is that the patients that are at risk, more severe disease, longer in the hospital, older age. Those are really probably your three big risk factors here. So keep that in mind when you're seeing your patients after they survive COVID. Thank you. tackle the second part of this session, which is the prognosis and treatment options for post-COVID-19 ILD. My name's Claire McGruder. I'm an assistant professor of medicine at Columbia in the ILD program. I have nothing to disclose someday. My objectives today are mainly to help all of us understand what happens when we get one of these patients that has ILD on CT scan after having had COVID. What should we expect? What is going to come of their lung function? I'm going to help identify interventions that might prevent COVID-19-associated ILD, treat COVID-19-associated ILD. And then, in my opinion, most importantly, I really want to highlight some future directions and questions that might remain unanswered in this field. So ILD from COVID, just like ILD from, as we know it, outside of COVID, is a very heterogeneous entity. That being said, post-COVID ILD can encompass anything from ground glass opacities, post-COVID or post-infectious organizing pneumonia. And it can go anywhere to what Dr. Kershaw was saying, fibrosis, architectural distortion. So I just want to make note that what we are going to expect of the prognosis and the treatment options are going to differ as well. I'm sure many of you have read literature that likens post-COVID ILD to fibrotic ILD and pulmonary fibrosis. Of course, we know that there are shared demographic factors like advanced age, male sex, smoking, chronic lung disease. There was a great paper in the ERJ that talked about the shared genomic risk factors between IPF and COVID-19 ILD. Transcriptomic studies have uncovered mechanistic processes that are shared between extracellular matrix deposition, excess collagen production, aberrant epithelialization. Short telomeres, which are a strong risk factor for IPF and progressive ILD, have also been shown to be associated with COVID-19 fibrosis. So it really begs the question, should we be expecting shared trends in progression? Should we be using the same medications that we use in ILD? And we'll tackle those questions now. So I'm happy to report, as Dr. Kershaw alluded to, the majority of post-COVID radiographic abnormalities resolve or stabilize. And this is across the board in every cohort study that has been published. This is a nice illustration of that in a publication in Radiology in 2022. This is three individuals that had CT scans from the acute phase on top. The bottom is six months, or sorry, the middle is six months and the bottom is one year. And you can see in each of these three patients, especially the left and central most patients, there is significant improvement over time. In the rightward most patient, their left lung improved significantly. The architectural distortion that we see in the right lung persists. And most of this change happens in the first couple of months after acute infection. These charts demonstrate CT scan involvement scores over time. And you see that anywhere from mild to moderate, severe, critical COVID, all of the improvement within all of these groups happens in the first couple of months. Of course, in severe and critical COVID, where the scores start out higher, you do see improvement over a longer period of time. But the trend holds true that most of the improvement happens very shortly after infection. These panes help us, again, break down what's happening to the imaging. The top left pane, again, shows this idea of somewhat of a plateau after about six to 12 months. The top pane talks about how many individuals have full improvement of CT scans, so normal CT scans. And at seven months, about 74%, sorry, 72% have normal CT scans. At 12 months, it's about 75. So again, we see that plateau at around the 6 to 12 month mark. And when we look into the patterns, that helps us understand why this might be. In both of the other panes, ground glass opacities are in blue. And you can see that there is a significant improvement in ground glass opacities over time. In the rightward most pane, the gray, which represents reticulations, that becomes more and more a part or the predominant pattern of the CT scans. And this makes sense, I think. What we think of as being inflammation improves, reticulations, which, at least in COVID literature, is often lumped with fibrosis or fibrotic abnormalities, persists. I think one of the still unanswered questions is, what do prolonged residual ground glass opacities represent? In many of these cohorts, we have individuals that have persistent ground glass opacities. A year out, their inflammation markers are down. Their symptoms have improved. They feel oftentimes great, but they have ground glass opacities. We don't, unfortunately, have a lot of biopsy data to help us answer this question, especially biopsy data that is outside of lung transplant explants or autopsy data. But this was a small paper out of Brazil where they biopsied individuals with persistent abnormalities and found that even in individuals where the predominant or only pattern is ground glass opacities, there's areas of fibrosis. So that's just to say, maybe this is still inflammation. It could also be potentially fine fibrosis that we're seeing. And I think this is something I would love to look into. And then Dr. Kershaw talked about this paper in the Blue Journal that was published earlier this year. And I wanted to focus on another part of it. So of course, this was a very large cohort, the COVID-ILD cohort out of the UK. And they identified 33 individuals that had longitudinal CT scans over time and, again, showed the changes in patterns. And you'll see here that, for the most part, the trend is stability or improvement. And I really want to highlight that you see two lines that are going upwards in trajectory in all abnormalities. So really, progressive disease is rare. Lung function mirrors what we're seeing in CT abnormalities in terms of this improvement and especially the vast majority of improvement happening in the first 6 to 12 months. That being said, it's important to note that a large proportion of individuals still have DLCO decrements after one in two years. In this cohort in radiology, at two years out, almost 30% had decrements in low DLCO. And the estimate ranges from 10% to about 40% based on the severity that are included in the cohort. And then the table 3 on the right is nice because they actually broke this up between individuals that had fibrotic versus non-fibrotic ILAs. And those with fibrosis were much more likely to have decrements in DLCO. And they were also significantly more symptomatic with a higher composite symptom score. So let's talk about therapeutic options now. This is the COVID update for 2023. And I really wish I had some bright, shiny COVID update for you guys in terms of treatment. But unfortunately, we're still on pins and needles waiting to hear about some of these studies. But I'll go over what we do know. Prevention of severe disease is going to be what prevents the majority of post-COVID ILD. Dr. Kershaw highlighted in his session that the single greatest risk factor for residual CT abnormalities across studies is severe infection. So how do we tackle this? The answer is vaccines. Of course, there's aspects of the COVID-19 virus itself in terms of mutations that might change the infectivity or transmissibility or severity of the variant. But really, across the board, we know that vaccines are upwards of 90% effective at preventing hospitalization. So that's a really good place to start. In terms of clinical trials for post-COVID ILD, there are many that are ongoing. And generally, you can lump them into one of two buckets. First is antifibrotics, nintenidib, perfenadone. There is one actually putting them head to head. And then people are also looking at anti-inflammatory. So this is your IL-6 blockers, your mTOR inhibitors, and the like. I'm now going to go sort of temporarily in terms of treatment. So in the acute phase, despite this being published in 2021, this is the only paper that I've seen that has looked at nintenidib in the acute phase during hospitalization. And this group looked at 30 individuals that were treated with nintenidib while mechanically ventilated and compared the 28-day survival and the days on mechanical ventilation to those that were not treated with nintenidib. And while they found that there was no change in 28-day mortality, they did have a significantly lower number of ventilator days. They actually had significantly higher P-to-F ratios and a lower proportion of high attenuation areas on CT scan. Now, this was a pilot study. It was very low numbers, 60 altogether. But it's interesting, and I would be interested to see if anything comes of this in the future. In the somewhat peri-acute phase of post-COVID, we have this entity of post-COVID organizing pneumonia. And of course, this was a really big article that came out in 2021. Everyone was really excited about it, that it was a prospective observational study that looked at organizing pneumonia. Basically, it was mostly ground glass on CT scan in individuals that had persistent symptoms after six weeks, at least, of having had COVID. And they treated these individuals with 0.5 mg per kg of prednisolone with a rapid three-week taper and found that despite this more quick treatment course than we would normally give for standard organizing pneumonia, they saw significant improvements in both dyspnea and lung function. And then when we get into the sort of post-post-COVID ILD, these are two Nintenib trials that I wanted to highlight that we're excited to see the results of. The first is NintenCore out of Paris, and the other one is ENCOVE1 in New York. These are both randomized blinded trials studying the effect of Nintenib versus placebo. The main difference that I've highlighted is that NintenCore is looking at individuals with lung function decline and fibrotic features only on CT scan. Whereas ENCOVE1 is for inclusion. They are looking at severe COVID survivors, but with CT scans that could have fibrotic or non-fibrotic changes. And the outcomes, the primary outcome for each is FPC decline, which again, mirrors much of our ILD literature. So currently there's no FDA approved treatment specifically for post-COVID ILD, but you can ask where does treatment of post-COVID ILD fit into the already established ILD or pulmonary fibrosis guidelines? And the answer is in progressive pulmonary fibrosis. These areas, or these arrows in the middle, show the various ways that one can meet criteria for progressive pulmonary fibrosis between spirometry, DLCO decline, and CT progression. Of course, the in-build trial that was in the New England Journal in 2019 looked at individuals that had non-IPF ILD, whether it be a fibrotic HP, unclassifiable ILD, CTD ILD, of course they weren't on immunosuppression, and they found that in these individuals that were treated with Nintenidib, they had a significantly slower FEC decline compared to placebo. So if we have individuals with COVID ILD that are showing progression, they would definitely qualify for Nintenidib. And you might be saying, Claire, you just spent the last 10 minutes talking about how these patients don't progress, and I actually stand by that. In my clinic, I actually find that when I see patients with post-COVID ILD that is progressing akin to IPF, I'm actually looking for other risk factors. I'm looking for short telomeres, maybe an underlying autoimmune disease. It's possible that they had ILD that was predated COVID and is now unmasked because of COVID. And then another unanswered question and that we get asked a lot, should we be biopsying post-COVID fibrosis? Would UIP on a pathology change management? Would this lower our threshold to be treating with antifibrotics? And I ask this because this is actually a really interesting, small, but super interesting study that came out of the University of Michigan, where they retrospectively looked at individuals that had surgical lung biopsies for post-COVID ILD. And they actually found that nine out of the 18 individuals that had surgical lung biopsies had UIP on pathology as the primary pathologic phenotype. Now, I really want to highlight that of the nine in the UIP cohort, four of them had a history of pulmonary disease or persistent respiratory symptoms beforehand. So you could argue that this could have been ILD that predated COVID-19, or at least put them at risk for severe COVID-19. But still, I think this is interesting. I'm not necessarily advocating for biopsying post-COVID fibrosis. I do not do it frequently, but it's a good mental exercise. And I think certainly if you happen to have a patient that already had a biopsy and there showed UIP, just given the worrying prognosis that comes along with that, many clinicians would have a low threshold to add on an antifibrotic. So just like with our normal ILD patients, the treatment of post-COVID-19 ILD patients is really multifaceted. These individuals often have multi-system symptoms. They qualify for this, what we call post-acute COVID syndrome. So the threshold should be low to refer to our colleagues in cardiology, neurology, psychiatry, and then using supportive measures, supplemental oxygen, pulmonary rehab, education, vaccines, all of those, along with disease-modifying treatments. That's how we're gonna take the best care of these patients. And of course, with Dr. Grewal coming after me, referral to transplant if that becomes, if they meet criteria for that. The conclusions of my discussion were, first and foremost, post-COVID ILD typically improves or stabilizes, and progressive fibrosis is rare. I think we really need to focus on what the risk factors are for progressive disease. Lung function also improves, but there's a large number of people that remain with deficits and DLCO. We are going to reduce post-COVID-19 ILD by reducing severe disease. And then I think fibrotic and non-fibrotic COVID ILD should really be approached differently and tentative, of course, can be used in progressive fibrosis. Whether there is a role for it in the acute phase, I think is yet to be sort of validated. And I think future studies really need to be precision-based. If we're lumping this heterogeneous group into clinical trials and expecting interpretable results, I think it's gonna be difficult to find positive trials. And so I really do think that fibrotic phenotypes and non-fibrotic phenotypes should be approached separately in order to get the most bang for our buck in terms of clinical trials and outcomes. Thanks so much. Thank you. Thank you for watching! Okay, good morning. Thank you so much for coming to this talk. I was just saying to Dr. McGruder, how am I going to follow that up? But I think I do have some ammo in my talk to try to follow it up. So I want to start by saying I have some news for you, then I have some good news for you, and then I have some great news. So with that sort of theme, let's dive into the current status of COVID lung transplant. My name is Harpreet Singh Grewal. I'm an assistant professor of medicine at Columbia University. I think my only disclosure that's not on here is I'm very mission-driven, like any transplant attending is to taking care of our patients, and I love what I do. So here are my objectives. We're going to take a look a little bit about COVID-19 and outcomes, and then discuss the referral process and selection process. I think it's very important to know where we sort of were, and where we are, and where we're going. And this is as of September of this year, the x-axis showing us timeline going from 2020 to September 2023. As you can see, the blue bars are weekly admissions into the hospital for COVID-19. They're continuing to decline. We're seeing these hills and valleys, but not as high as we were early on in the pandemic. When you look at the orange line, that represents deaths weekly per 100,000. So still we are seeing some deaths from this. It's much better, but it's not completely gone. So let's set the stage of how we think about candidate selection. That's a talk in itself, but I want to highlight a few key aspects of how we think about patients when we're thinking about transplant. In the most recent update of candidate selection guidelines, patients were bucketed into three different groups, those with absolute contraindication. These are patients with progressive multi-organ failure, patients who have active substance use, extremes of BMI, or untreatable or multi-drug resistant organisms which are infecting their lungs or their body that we cannot transplant. Certainly compliance, I think, is important and I'll highlight why that is later on. The second bucket is sort of substantially increased risk patients. These are patients that may need to go to centers that do transplants that are specializing in a particular process. This could be a dual organ candidate. This could be a patient that needs concomitant cardiac surgery at the same time as getting a lung transplant, among other things. So these are patients that are considerably at a higher risk for having unfavorable outcomes, should be recommended to go to centers that have experience that are specializing in these kinds of transplants. And then there's this bucket of patients who have risk factors. So thinking about patients that are advanced age patients who can have risk factors, but otherwise fairly robust patients. The other thing I think that was important that came out of the 2021 update was this ethical framework that we were given. When we think about transplant, we want to have successful transplant. That's the goal of any transplant physician that's, you know, working towards somebody getting to a transplant. And when we do an unsuccessful transplant, there is a potential alternate recipient that could have had a successful transplant, given the prevailing shortage in organs. So it's something that we often keep in mind, and it was a big question during COVID as well. So what does an evaluation look like? This is something that's a typical evaluation. Certainly when I see patients, they go through something like this. I sign, I think it's like 76 orders or something that goes from all the consultants and the blood tests and CAT scans. So highlighting this because it's important to note that when somebody's critically ill with COVID, we can't do all these evaluations, and there are challenges. I think the biggest one that comes up is consent. How can we get informed consent in patients who are mechanically ventilated, sedated, and put them through transplant, and then expect them to take care of themselves and take all the meds and do all the follow-up? Certainly, you know, psychosocial evaluations are limited. Their healthcare maintenance is limited. Imagining a patient, you know, who hasn't had a colonoscopy could have a premalignant polyp that gets missed, and subsequently on immune suppression can be a very poor outcome. There are other limitations, but certainly things that we had to be mindful about when we were thinking about these patients. So last year when I showed this slide, I had separated these patients out into the sort of the two phenotypic patient populations that we saw, and there's going to be this sort of shift. So when we see transplant patients, either they're intubated, or they're on ECMO intubated, or they're debilitated in the hospital on high flow, or there's those patients who are ambulatory working towards rehab, and then there's this sort of outpatient group, as my colleagues Dr. Kershaw and Dr. McGruder alluded to, that either had ILD that got unmasked, or they progressed, and we didn't know about it, or they developed COVID in some form post-infection, sorry, pulmonary fibrosis post-infection, and they could travel back and forth depending on if they got better, or if they had a secondary insult, they could get sicker. So now in the transplant literature, we've sort of kind of put these two patient populations into these two separate buckets. So they are the COVID-19 ARDS, and the COVID-19 pulmonary fibrosis. It's important because I'm going to show a little bit of data on this later on. Again, there's no such thing as a perfect category, there's obviously overlap, but just for purposes of understanding where we are with these patients. So the other, I think, big question during COVID was ECMO utilization. This is an updated slide from the last year's slide. As you can see, the ELSO dashboard collects data from all around the world. The top left side, you're seeing 15,000 runs done, and the mortality around, the mortality around, in-hospital mortality around 48%. And then we wanted to take a look at the U.S., or I should say North America, and again, similarly, 48% when we look at 10,000 plus runs. There was a study that was published in 2022 that looked at 18,000 patients in 52 studies. Again, pool mortality around 48%. So coin flip, if you're going to go on ECMO about survival, and then you really need to have an exit plan. You need to have a collaboration if you think these are patients that are going to need to go to transplant, certainly patients that are going to get stuck. I would say that a good collaborative exit strategy is extremely important when you're thinking about ECMO in these kinds of patients. So what experience did we have? This is a slide, again, I showed last year. We had some experience of doing lung transplant in ARDS, so non-COVID ARDS. And then between the 13-year period, 2005 to 2018, 39 patients were transplanted with the indication of ARDS in hospital mortality about 10%. And then on the left side, you can see survival even up to three years when we compare them to restrictive lung disease, similar. So overall acceptable results, some experience before we got into the COVID pandemic. Early on, there were recommendations by the experts in the field, as well as subsequent IHLT task force that made recommendations on how we think about these patients, how we should consider them. Again, these were early on, so very focused on the inpatient setting, the acutely ill population. Candidates should be generally younger. They should have enough time to show us that this is irreversible injury. Early on, this is the question. It was unclear. Nobody really knew the answer. It was somewhere between four to six weeks was what was recommended at the minimum to wait. Showing radiographic evidence of irreversible lung injury, as we now know, those get better. So it's very difficult also in the acute setting, I think, to say what is fibrotic and what is not. And they have to be somewhat awake, preserve neurological status, you know, to be able to participate in rehab or conversations about a lung transplant than certainly being able to participate in rehab and not having some of those absolute contraindications that I showed you. So a lot of sort of overlap with certain added caveats subsequently about COVID-19 testing being negative on deeper samples. So how do we navigate these patients? This slide's changed. Again, can't take a patient, put a lung in who has multi-organ failure. We can't fix the other organs. Certainly not a good idea. Patients who are, you know, having uncorrectable DICs, actively bleeding, not doing well, active infections that are not controlled. Compliance, again, difficult question to answer. And recent malignancies or active malignancies in the acute setting. There was always this question of sweet spot where that is. And I think that I should highlight that there were these reports of the so-called ECMO long haulers. These were patients who were on ECMO for months and then subsequently got better and got off ECMO. That pushed us a little bit, gave us a moment to pause before we started considering transplant. We were around six weeks. I think that number is getting pushed further and further out. Certainly there's a risk benefit because a candidate can become a non-candidate because they can develop complications. They've been in the hospital. So there's always this back and forth juggle, hence a close collaboration with your transplant colleagues and continued evaluation I think is extremely important. So I think that number is now closer to eight weeks before we should really start to talk about transplant if you have somebody on ECMO. So again, what's the UNOS data showing? This came out in 2022. We wanted to make sure as a community that is transplanting, are we able to sort of replicate the same outcomes? As you can see at that time, 7% of all transplants done in the United States between August 2020 to September 2021, representing 7%. Again, survival around 92% at six months, which was acceptable. So what's happened? This is work that was done by our group at Columbia. We want to look at the pattern of the pandemic and in context of transplant. In total between March 2020 and December 2022, 578 patients were listed. So these are patients that have gone through the evaluations and are on the list actively waiting for an organ. And this is where it's I think important to highlight the words COVID ARDS and COVID pulmonary fibrosis. When we enter patients into the United Network for organ sharing, they have to have an indication for which they require lung transplant. And that indication was updated later on in October of 2020. So before that, there were 32 patients that we found that were transplanted for ARDS during that time. So we wanted to include them to try to capture as much of that population as possible. Again, 83% that got transplant, younger patients, 51, half of them were on ECMO, majority were double lung transplants, waitlist death around 9%. When we look at the waitlist death, if you had COVID ARDS, your risk of dying while waiting was two-folds higher compared to COVID pulmonary fibrosis. So something important to note as I highlight the patterns going forward. Again, some patients were removed from the waitlist. Either they were sick or they got better. And then there are patients who remained on the waitlist at the time of this eval. So as you can see, this is going back from 2020. And then if we go forward to 2022 December, there has been an overall decline in number of patients that are needing a lung transplant for COVID-19. So let's look at this a little bit deeply. Let's look at what's happening at the time of listing. So again, the x-axis represents time from March 2020 and all the way up to December 2022. So first, number of patients on mechanical ventilation continues to decline while waiting for an organ. What about COVID ARDS diagnosis? So these are patients that are getting listed in the UNOS system. Again, declining going to essentially zero. What about ECMO? Sorry, COVID ARDS and ECMO going down again. Decline. So what are we seeing? What's new? So this is what's new that sort of started to separate out. These are COVID pulmonary fibrosis patients. So these are patients that are either on oxygen or waiting, but not necessarily in the ICUs, but not good enough to be discharged. Or are they? So we wanted to further look at what's happening at the time of transplant during this period. Again, similarly validating that patients on mechanical ventilations are decreasing. ECMO patients are decreasing. Patients with mechanical ventilation are decreasing ARDS overall. What's happening to COVID? Again, pulmonary fibrosis diagnosis are increasing instead of the COVID ARDS. And patients are getting discharged. So these are patients that are not in the hospital. The number is increasing with the diagnosis of COVID-19 pulmonary fibrosis that are waiting for transplant. So a very clear shift from the acute COVID ARDS population to the COVID pulmonary fibrosis patients. So how do we think about dealing with these new group of patients that have been dubbed with the COVID-19 pulmonary fibrosis or in some form of that ILA type physiology and findings? They're being followed by my colleagues in the ILD clinics. And I think they need to follow the usual pathway. They need to have their baseline valves done. If there's a consideration for trial of steroids or antifibrotics or even a trial that they are potentially eligible for. And at the same time, I think optimizing their comorbidities is extremely important because we don't want to go to the marathon on the day of the marathon. We want to practice and be ready for it. And despite all of our best efforts, they're getting progressively worse. Worsening oxygenation, developing new oxygenation, or developing pulmonary hypertension, for example. I think it's okay to refer to them. We're happy to have this conversation. So now to just close out and give us some closure back to what all of this has done and where we are. Again, this is a slide that I showed earlier. Again, survival initially was promising. So teams across the world, across the country, continue to transplant. I want to now just kind of highlight some of the nuances of these transplants and newer data. So this paper is an interesting paper that was from January of 2009 to March 22 that looked at patients in the database and compared patients who had COVID ARDS, sorry, COVID, non-COVID ARDS and COVID lung transplants. And they looked at outcome. Again, no difference in sort of the longer term outcomes at one year. What about looking at patients during the pandemic who had a transplant who had COVID-19 and those that were transplanted for other reasons? Again, similar one year survivals. Well, what about looking at the difference between COVID-19 pulmonary fibrosis versus COVID-19 ARDS within that same population? Again, no big difference and overall survival essentially similar to the non-COVID ARDS, non-COVID lung transplant population. So this paper out of Penn that was recently published looked at it even in more detail. We wanted to see, okay, when we look at patients between this pandemic period 2020 to 2022, what's happening when we compare COVID ARDS group with COVID pulmonary fibrosis and the non-COVID. Again, similar to what others have found, no difference. Then they wanted to look at patients just on ECMO with a COVID diagnosis, even if they didn't have a COVID ARDS diagnosis, they were on ECMO and non-COVID ECMO, or sorry, COVID patients not on ECMO. Again, similar outcomes. So I hope in this talk I've conveyed to you that I think continued collaboration is extremely important. Being partners, having good ECMO protocols, planning is extremely important. I think the indications are not changing as we've seen the shift towards the interstitial lung disease population. Patients are more so on the outpatient setting. We're doing transplants less emergently for this indication. We have more time to evaluate these patients. So I think overall we're doing better as a community, as a whole, taking care of these patients. And certainly we're seeing similar outcomes between COVID-19 and those without COVID-19 for transplant. And I wanted to say thanks to my mentors, my colleagues, my patients for whom I do all this. Thank you.

interstitial lung disease

COVID-19 infection

lung transplant

CT scans

abnormalities

prognosis

treatment options

collaborative care