Kicking off a new season of In Pursuit, Dr. Patrick Seed talks with Dr. Bria M. Coates about her research in pediatric critical care medicine and respiratory infections in children. Dr. Coates shares insights into the challenges and unpredictability of viral respiratory illnesses in young patients, the impact of these infections on long-term lung health and how her research aims to reshape the field.

Guest: Bria M. Coates, MD, Attending Physician, Critical Care Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago; Crown Family Research Scholar in Developmental Biology, Ann & Robert H. Lurie Children’s Hospital of Chicago; Assistant Professor, Department of Pediatrics, Northwestern University Feinberg School of Medicine

Host: Patrick C. Seed, MD, PhD, FIDSA, Attending Physician, Infectious Disease; President & Chief Research Officer, Stanley Manne Children’s Research Institute; Children’s Research Fund Chair in Basic Science; Professor of Pediatrics (Infectious Disease) and Microbiology-Immunology, Northwestern University Feinberg School of Medicine

Show Notes:

  • Winter is a time when respiratory infections increase and in 2024/2025 cases of RSV, whooping cough, and severe walking pneumonia have landed many Chicago-area children in the pediatric intensive care unit.
  • Recent years have proven to be challenging in predicting the different patterns in respiratory illnesses. Dr. Coates notes the possibility that the COVID-19 pandemic may have a role, as children and communities at large weren't sharing potential pathogens during that time.
  • Dr. Coates’ research explores why some children recover quickly from respiratory infections while others face prolonged ICU stays.
  • There are potential lifelong impacts from severe childhood respiratory infections on lung function and overall health, which include asthma and decreased lung function and increased risks for chronic diseases in adulthood.
  • Part of Dr. Coates’ research investigates nasal cell responses to illness and how these cells might predict disease severity. Her research indicates that the children who recovered quickly from severe illness had more resilient progenitor cells.
  • Dr. Coates hopes her research could lead to tools that provide healthcare professionals more accurate information and data for treatment in the ICU. She is looking into how existing medications might be repurposed to improve outcomes.
  • As a physician-scientist, Dr. Coates shares that caring for critically-ill children while driving research forward is both challenging and rewarding. Her weeks in the ICU drive her desire to explore creative solutions and better understand disease.
  • Dr. Coates notes that there are disparities in severe viral infections among communities with fewer resources. She urges colleagues to consider efforts to help these vulnerable populations community-based prevention strategies and find ways to provide equitable healthcare access to all.  

Transcript

[00:00:00] Dr. Patrick Seed: Welcome to In Pursuit, Research Perspectives from Ann & Robert H. Lurie Children's Hospital of Chicago. I'm your host, Dr. Patrick Seed, President and Chief Research Officer of Stanley Manne Children's Research Institute, one of the nation's largest pediatric research centers. In Pursuit is our opportunity to learn about the groundbreaking work of our researchers and to join them in their journey as they strive to improve the lives of children and families in Chicago and beyond. We are so excited to kick off Season 2 of our podcast. Our guest today is an expert in pediatric critical care and respiratory tract infections in kids, a topic that's really front of mind for many parents, caregivers, and health professionals this time of year. She's an attending physician for critical care medicine and the Crown Family Research Scholar in Developmental Biology at Lurie Children's. She's also an assistant professor in pediatrics critical care at Northwestern University Feinberg School of Medicine. I'm very excited to welcome Dr. Bria Coates to the podcast. Welcome, Bria.

[00:01:01] Dr. Bria Coates: Thanks for having me.

[00:01:02] Dr. Patrick Seed: Absolutely. This is the time of year that it's top of mind , both for those of us who do healthcare for children, but also certainly the parents and caregivers, what's going on in the season with respiratory tract infections. And so talk about what you're seeing this year, thinking about sort of the wild ride that we've been on the past number of years, where we obviously went through a pandemic and then we had a quiet year and then we had the triple demic with Covid, influenza, and RSV, and then we had another quiet year and then here we are this year. What are things looking like on your side of the world clinically?

[00:01:34] Dr. Bria Coates: I think given the unpredictability of the last couple of years, it feels a little bit challenging to know what to expect. So I think those of us particularly who work in the ICU and normally would be starting to see respiratory infections ramp up this time of year are really, a little bit more anxious because we don't necessarily know what to expect anymore. Every time we think we can predict what's coming, we're wrong. However we have started to see our typical infections start to rise in the ICU. I'm starting to see infants in particular sick with RSV Respiratory Syncytial Virus and our typical other cold viruses. It's coming and I think the biggest question at this point is how much of it?

[00:02:19] Dr. Patrick Seed: It's been in the news, obviously, that there have been a few unusual things this year. I think we're having in Illinois and particularly Chicago, an outbreak of pertussis, which for everybody is whooping cough. And then also we're seeing like a lot of walking pneumonia is even making kids who typically we wouldn't think of being affected very much either getting the infections but also getting more severe infections. Is that something that you're seeing also clinically?

[00:02:42] Dr. Bria Coates: Yes, absolutely. We've seen many more cases of infections with mycoplasma, which is one of the bacteria that we typically think of as causing walking pneumonia. Normally that actually doesn't make its way into our ICU hence the name walking pneumonia and not hospitalized pneumonia, but we have even been seeing some kids sick enough with that disease to end up in the ICU. So that is really unusual for us. We've been lucky enough not to have the whooping cough reach us yet, though I have certainly seen very severe cases over the course of my career where children have died or have almost died from whooping cough. So that surge is quite concerning to us, and potential implications for what that means about how parents are vaccinating their children?

[00:03:29] Dr. Patrick Seed: Yeah, I think it's probably the vaccine rates, isn't that what you think as well, for the pertussis at least?

[00:03:34] Dr. Bria Coates: That would be definitely my worry, is that we have fallen below our previous rates of vaccination that was keeping children safe from pertussis. And given how severe that can be, especially in young babies, it's quite frightening to us in the ICU.

[00:03:47] Dr. Patrick Seed: Before we move on sort of thinking about the epidemiology of what's going on. Do you have any theories of why we're seeing the more severe mycoplasma walking pneumonia or I like your hospitalized pneumonia, hospitalized laying flat pneumonia.

[00:04:01] Dr. Bria Coates: We have certainly been surprised multiple times over the last couple of years at the different patterns in respiratory illnesses that we've seen and the different surges that we've seen post pandemic, which certainly makes you wonder if the time during the pandemic where children weren't sharing these potential pathogens or communities at large have led to a different rate of spread to the communities and a different pattern of spread through the communities such that there's more vulnerable populations being hit at the same time but It's not obvious what the explanation is, but it feels a lot like, a year or two ago we saw a big surge in Group A strep, which is the bacteria that causes strep throat, and we saw some very sick children with that. And this surge now with mycoplasma feels similar in that two things that we see periodically, but not usually to the same numbers.

[00:04:53] Dr. Patrick Seed: I know a topic that we've had the opportunity to talk about before, which is the tale of two children, right? You often will see two toddlers or infants who by all likes seem like they should be similar, right? And one, in this case, I'm suggesting both of them are sick. They both end up in the hospital and maybe even with some time in the ICU. But one seems to recover quickly and then one goes downhill. So what I was interested in is first, can you just describe for everybody a little bit about those kids, what ICU when they come in, set the stage for them, and then talk about that child who maybe doesn't recover as well and what might happen with a severe viral respiratory tract infection?

[00:05:33] Dr. Bria Coates: Yeah, so these respiratory viruses cause a very wide range of illness. Some of them will infect a person and just cause a runny nose, and some of them will move down into their lungs and cause a viral pneumonia, which leads to much more severe disease. And in children, for reasons that we don't understand, we see both ends of that spectrum. Though infants are at higher risk of the more severe disease. What we see when babies come in with some of these viruses, classically RSV would be the most common one, but we definitely see it with lots of others, including the most common cold virus, rhinovirus. Is that babies will come in with symptoms of an upper respiratory infection, so lots of secretions in their nose, and then it progresses to trouble breathing, so they're breathing fast, they're breathing hard and using extra muscles to try to breathe. And we have different ways to support them. One is just suctioning those secretions out of their nose to help them breathe. But as they get sicker, we have different ways of delivering oxygen to help the air going into the lungs and coming out of them. And for lots of babies, that's plenty. So we call it, high flow nasal cannula And they sit on that relatively non invasive device for a couple of days, and then they go on their merry way. But there's a subset of children who come in looking like that, but then even with that support from oxygen breathe harder and harder to a point where they can no longer breathe on their own, and we have to take over for them. So for those babies, that's a breathing tube that goes down their throat, down their airways, into their lungs, and we have to hook them up to a mechanical ventilator to breathe for them. Some of them get better quickly, but some of them might be weeks on a ventilator before they're able to breathe on their own again. And that, distinguishing between those two babies, the one that just needs a little oxygen and then goes home, and then the one that requires a ventilator is really challenging in the first day that they're with us.

[00:07:25] Dr. Patrick Seed: Yeah, it's got to be difficult to talk to the families and knowing in the back of your mind that you want to hope with them for the best outcome, but know that there's some level of risk. Talk a little bit about that. When you think about those clinical scenarios, what are the types of research questions that sort of have come to your mind and have led to research passions?

[00:07:45] Dr. Bria Coates: For most of my training, the fact that babies would end up in the ICU with a viral respiratory infection was accepted as just fact that they were young, they didn't have an adequate immune response and they would end up in the ICU, and every year they would fill up our ICU. And I was struck by how there was not much questioning that inevitability . That we just accepted it as part of being a pediatrician. And so my research questions really drove from that. Why do these babies get so sick with these viruses that can be incredibly mild in other populations? And can we do something about it and not just accept that this is part of their growing up. So my research questions have started from just that most simple of that is why. So why are babies getting so sick with these viruses? Is it just because of how small they are? Or is it something more about the way that their bodies respond to the virus? And of course, could we do something about that? And then also, what's different, because as you mentioned, not every baby who gets a virus ends up in an ICO. It's certainly a minority of babies that get these viruses. What in particular, What is it about those children that have set them up for more severe disease? What can we do about it? And then what are the long term consequences? And I think our lab has been thinking more about that as more and more research shows that severe viral pneumonias in childhood have potentially long term consequences on lung health throughout life. And are there ways that one can we treat the acute infection in a different way that shortens illness and shortens severity? But two, can we come up with strategies or interventions that would promote healthy lung repair such that after these events that children don't have those long term consequences of decreased lung function that could impact them for the rest of their lives?

[00:09:35] Dr. Patrick Seed: I do think most people have this idea like you said not only is getting severe infections just a matter of life as some children, you know, it just happens and there's not much more of an explanation than that. But I think people also have this idea, right, that children have this incredible ability to heal and resolve. These problems that they have in a wide variety of organs, the lungs, the heart, the liver, kidneys, the brain, et cetera. But that's really not the whole story. What are those long term consequences that some babies might come out of a severe infection with?

[00:10:04] Dr. Bria Coates: So for a long time, we've known there's an association with asthma. Up to a third or a half of children who have a severe viral infection, respiratory infection in childhood will develop asthma. Some of those children will get over their asthma in childhood and some of those children will have asthma for the rest of their lives. But what is becoming more apparent in recent studies is some children who don't get asthma will have decreased lung function. So when followed over time their lung function will not reach its full potential. SoTheir lungs are still growing as with the rest of their body and really optimal lung function isn't achieved until late adolescence or, you know, early adulthood. And some of these children who have these severe infections in childhood never reach that optimal lung function. And that has consequences. that we know from adult disease that if you start out with suboptimal lung function in your early 20s, you're at higher risk for chronic obstructive pulmonary disease or COPD even if you don't smoke. You're at higher risk for heart disease and at higher risk for a shortened lifespan. Making this increased recognition of those potential life long consequences of lung function is really drawing more attention to how children heal from these infections can we help the children who are not going to adequately heal and promote more healthy repair so that they are able to achieve that optimal lung function in their late adolescence, early adulthood?

[00:11:32] Dr. Patrick Seed: It sounds like in describing these long term effects and then, of course, certainly that this early issue of which child is going to go from snotty, and just looking sick at home to needing what you described, which is really profound care right, to support them through and then potentially being at risk of now lifelong lung problems. The cheeky thing, of course, would be for me to say what's the answer, Bria? But knowing how long it takes to do the research, can you just talk a little bit about what do we know at this point when you take those two children that have these totally different trajectories of, how they're going to handle this infection. Tell us a little bit about how your works inform that and, where are we in terms of understanding some of the answers to that?

[00:12:17] Dr. Bria Coates: So our work in trying to tease this apart has started with a sample collection method that we can do in all children. And so that is scraping the insides of their nose. What we would really love to know is what's happening in their lungs, in their lower airways. But we don't have access to those in most children but we do have access to the nose. We've been investigating samples there. And there is data to suggest that the response in the cells lining the nose to viruses does reflect some of the responses lower in the lungs to the same viruses. So we can learn stuff not just about the nose which is important, but also potentially about what's happening in the lungs by sampling those cells. So we did a study a few years ago where we scraped the noses of children admitted to the ICU and then tested how their cells were responding to the virus and whether or not that response was different in the children who recovered within a couple of days and the children who either went on to require more invasive support Or took longer to recover in the ICU. And we found some interesting signatures in the way that their cells were responding to the virus that distinguished between those populations. If I scraped a baby's nose on the day that they came into the ICU i t looked very different if they were going to be gone from my ICU in two days than if they were going to be there for another week. And what we saw was that there was an increase in the damage to the ciliated cells, which are one of the major cells lining the nose, but also a major target of these viruses. And there were an increase in those cells and their attempt to repair compared in the children were going to be sicker, go on to be in ICU for longer than the children who were not. And in the children who got better quickly, there was more of the stem cells of the nose, more of the progenitor cells that can repopulate the nose. Which we found really interesting because that imbalance between damage, And recovery has also been shown to be present in other lung illnesses. So the more progenitor cells that are present tends to predict a better outcome in some other lung diseases as well. It seemed to us that the children that recovered quickly had more resilient progenitor cells in their nose. And we also saw in support of this increase in repair pathways, specifically DNA damage repair pathways in the children that recovered quickly, again, pointing towards a more resilient phenotype in those children.

[00:14:55] Dr. Patrick Seed: That's amazing. It raises a number of different questions, right? Is there something that is diagnostic in that? Do you think that there's information there that you would, not tomorrow, but in time would be able to bring to the bedside and say, this helps me because I can do this test. I can get a little bit of a swab from someone's nose and get some information that tells me, this is a child I need to give more support to, or I need to give a different therapy that would help them not have this bad outcome or long hospitalization versus the child, like you said, who's going to get out of the ICU in the next day or two.

[00:15:29] Dr. Bria Coates: Absolutely. And I think, we're a bit of a ways off from this, but. If we could identify these signatures, if we could replicate them in larger cohorts and say that consistently the babies that get better faster look one way and the babies that are going to be sicker look another way, it would help not just with, being able to talk to the families when they come into the ICU, but also I think in managing their therapies because there is always the potential to guess wrong in the ICU and to over treat a child who would have gotten better no matter what you did. And I think this sort of adjunctive information could help you feel better about delaying a more invasive therapy potentially because you're pretty sure that the patient is going to get better without it, as opposed to being more worried about a patient and maybe moving a little bit faster to doing something more invasive because their potential for getting sick was higher and you wanted to be ahead of that and not have to wait until an emergency happened. So I do think that sort of prognostic data that could come from these sorts of tests would be incredibly valuable.

[00:16:34] Dr. Patrick Seed: Yeah, it sure sounds like it. If for the children whose cells the information you're getting from those cells is telling you, okay, they're going to have a rougher time, right? They're going to be in the hospital longer and maybe have some of these long term risks and things. Are you seeing signals from those cells of things that you think there are currently medicines that exist or that are coming into existence that will help you with that? Or do we need to invent some new things, do you think to, actually then also do different therapy than we do now to support those children?

[00:17:03] Dr. Bria Coates: I think potentially both. We do see some Inflammation signals that do have some medications that are used for other purposes that potentially could be repurposed for this disease. And that part's really exciting because obviously it's a lot easier to be able to reapply an already approved and safe medication to a new patient population. I also think, though, that there will be the potential to find new pathways to target that are unique to these young children with these viruses that could make them more resilient to the disease, recover faster, and have more healthy lung repair after they're infected. That potential is very exciting to us.

[00:17:51] Dr. Patrick Seed: That's incredible. That would be a real game changer. It seems like for a lot of these children. You were part of a NIH panel, weren't you, recently that was convened to, think about these young children who have respiratory viral infections were there any insights that came from that where you thought they were, particularly important questions or intersections with the work you're doing that, this national group focused on this problem raised up together?

[00:18:16] Dr. Bria Coates: Yeah, that essentially kind of a brainstorming session or sharing of ideas about where the gaps in knowledge are about these illnesses you know, these viral infections in children. I think it was very interesting and helpful to hear different people's perspectives on what the key players are because every researcher has their favorite cell and to see how, the interplay between all of the cells in the nose, the airways, the lungs might be playing a role in severity of disease and outcomes. So coming together as a group was a great opportunity to identify where the field needs to go to move forward. And one of the initiatives that came out of that meeting was a new funding opportunity from the NIH with the goal of enrolling up to, I think, 1500 children under the age of two admitted to the hospital with one of these viral respiratory infections. And to follow them for at least three years in the first iteration of the project. And the hope would be that by focusing on these children who have not been previously studied in depth, that we would be able to apply some of the more advanced cellular phenotyping and immune phenotyping technologies that have emerged over the last couple of years to better understand what's happening with these children and identify pathways that could be targeted with drugs that exist or medications that exist or identify the pathways that would be most beneficial to create new medications for. So that's a really exciting opportunity. And I think something that's been a long time coming that these children really haven't been focused on before.

[00:20:01] Dr. Patrick Seed: Yeah, it sounds like a terrific opportunity. It occurs to me that being a physician scientist in the work that you do you're getting this surge of children who are really sick at the same time that you're trying to do that research. How do you balance that? Like, how do you put that all together? And obviously you also have a family as well to tend to. Tell me a little bit about that because it's impressive.

[00:20:22] Dr. Bria Coates: It's definitely not always easy, that's for sure. I really do enjoy taking care of these patients in the ICU um, they do drive my desire to make things better. The joy and satisfaction that I get from taking care of these patients, but also the frustration I get from not having tools available to me to make them better, faster, is what drives my research. Instead of thinking of it as a balance of the patients need me and the research need me I actually feel like it's more of a motivator that the patients need me and therefore I need to do the research. I don't necessarily struggle between taking care of the patients and doing the research. It's more, I feel after I spend a week taking care of patients, I'm re-motivated to think harder about the problems in front of us and look for creative ways to better understand the mechanisms driving these illnesses in our patients.

[00:21:16] Dr. Patrick Seed: this is a Chicago story even though I know we talked about this being a national story. I'm curious, what is doing this work in Chicago what's this backdrop of Chicago mean and how's it influenced the work that you do?

[00:21:28] Dr. Bria Coates: Chicago's a big city and so, we know that what we saw with COVID was that, severe viral infections do not necessarily affect all communities equitably, and that actually turns out to be true with some of these other severe respiratory infections, and that living in places in Chicago with lower child opportunity and decreased healthcare resources is a risk for developing these severe infections and ending up in our hospital. Working in Chicago does raise that awareness of the inequality that we see in children hospitalized for these viral infections and the need to think about ways outside of the hospital that we can work in the communities to prevent children from ending up with us in the first place. I do think it's also important for us to think about things in the community that increase the risk for the infection the first place and what we can do to support those communities at highest risk to try to protect these children from these illnesses.

[00:22:33] Dr. Patrick Seed: Incredibly important dimensions, The prevention as well as the diagnosis and the treatment are really key. So thanks for adding all of those. Bri, it's been really amazing having you on the podcast today. I'm appreciative that you took the time and we got to hear your story about your fantastic research and, and how you put it all together with your clinical work.

[00:22:52] Dr. Bria Coates: Thank you. It's been a pleasure to talk about all this.

[00:22:54] Dr. Patrick Seed: For more information on Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago, visit our website, research.luriechildrens.org.