Thomas Wallach, MD, and Janet Rosenbaum, PhD, on Pediatric IBD Trends During the Pandemic

Drs Wallach and Rosenbaum discuss their study into the trends of IBD incidence among children in New York City during the COVID-19 pandemic, and their surprising findings.

Thomas Wallach, MD, is a pediatric gastroenterologist the Downstate Health Sciences University in Brooklyn, New York City. Janet Rosenbaum, PhD, is an epidemiologist at Downstate Health Sciences University.

TRANSCRIPT:

Welcome to this podcast from the Gastroenterology Learning Network. I'm your moderator, Rebecca Mashaw, here today with Dr. Thomas Wallach and Janet Rosenbaum from the Downstate Health Sciences University in Brooklyn, who conducted an epidemiologic assessment of pediatric inflammatory bowel disease in New York City during the COVID-19 pandemic. Thank you both for joining us today. So to start off, what led you to choose this as a topic for research?

Dr Thomas Wallach

I'll jump in. When I arrived in Brooklyn in 2020, after completing my training at UCSF, I was really struck by the number of new pediatric inflammatory bowel disease, or IBD, diagnoses that we were making. We had quite a few of these patients where I trained and my experience was that patients that you were suspicious of, that you would proceed to endoscopy, a certain percentage you would end up finding evidence of disease. And what I was noting here is that not only was I encountering a lot of patients that I was suspicious of in proceeding to endoscopy, but a very high fraction of them were turning out to actually have Crohn's disease and ulcerative colitis. And I was a little bit struck by that. There's clearly going to be some artifact from people weren't seeing specialists for a few months and possibly there's something else there.

But we'd started to hear some case reports about COVID linking with other autoimmune diseases and we'd heard some other literature points that started to make me suspicious that other things could be happening here. And then there was the fact that a lot of people classically attribute this IBD pathogenesis to some sort of inflammatory trigger, which viral infections are commonly thought of one. And we really, on the whole, actually had a lot less viral infections in 2020 in New York than we really would ever have normally. And I thought that this was a very nice natural experiment to look at. If we could get data from the entire city and really look at overall rates, we might be able to see if there was an alteration that was occurring.

Dr Janet Rosenbaum:

And from my standpoint, I began the pandemic interested in what the long-term effects are. Because as an epidemiologist and going way, way back in my education, I knew about the long-term effects of the 1918 flu, that there was increased rates of schizophrenia in children who were in utero during the flu if their mothers had the flu. And I knew of longer term effects on a number of diseases. Even in the 1950s and '60s there was a peak in heart attacks and there was a long debate about whether that was due to the 1918 flu. So I just have this very large global perspective and I started out the pandemic doing a lot of research into long COVID and what long COVID could look like, looking at the effects of long SARS and long MERS because they had been following these cohorts for many, many years, from 20 years ago now.

So that was my standpoint coming to this project because there could very well be a lot of long-term effects. And a lot of them we may never know. It may still be a matter of debates in the long-term, but this is a really concrete projects that we can look at.

GLN:

Your research article says you started with the hypothesis that the perceived role of infection is one of the possible triggers for IBD, and that should have caused incident rates of UC and Crohn's to drop, as you explained Dr. Wallach because the incidence of all infections decreased, I presume, because people were masking and kids weren't in school. So they weren't getting the flu, they weren't getting a lot of colds, they weren't getting the usual range of childhood illnesses. So that's where you started from. It's like, why are we seeing more IBD when in fact we really should be seeing less?

Dr Thomas Wallach:

Yeah. At this point, the pathogenesis of IBD is still for the most part, not really none. There are definitely variations of it that have what we call monogenic causes, so there's one gene that causes this. That's the very small subset of people with IBD. For the most part, there's some things that are probably genetic. We know there's an increased risk in families. We know there's some other things like that. But we don't really get what happens to create this disease from someone whose intestine previously worked normally.

One of the big hypotheses that people have been kicking around for a while is that there's an inflammatory trigger, so like a viral infection or bacterial infection. And overall, especially in the post vaccine era, like all vaccines, bacterial infections are just way, way less likely. So viral infections are a big cause. And we know that all the non-pharmaceutical interventions undertaken, especially at the beginning of the pandemic, just obliterated influenza, almost every other communicable respiratory and gastrointestinal virus.

Because to communicate those things, you have to be seeing new people in environments where you can spread them in between mass closures, people not moving around very much. Those exposures were just so much less they were not spreading. And you can track that in a variety of different measures. One of the most strong ones looking at something called influenza-like illness, which gets reported to government at various different levels. And we just see those things collapse. Multiple lineages of flu became extinct. We know that this happened.

And one of the things that we could test with this study looking at this was to see do we just see that there is an overall decline that would support that viruses were a big pathogenesis factor? Or we could say, do we see no change? Which would be a little bit harder to interpret or a clear increase which would suggest that there's a really specific risk from COVID. And we sort of ended up sort of at the no change, a little bit of an increase, suggesting that COVID does have a very significant specific risk, but that it's not necessarily that different from other common viruses that can cause this or thought to be related to this, like adenovirus or other things like that.

GLN:

Would you give us a general overview of the project, just the parameters, how many patients or subjects were involved and what primary outcomes and questions were you looking at?

Dr Thomas Wallach:

Sure, I will let Dr. Rosenbaum come in here a little bit because a lot of this is I think going to be about her methodology. But what we did to start off with this was to build a consortium among pediatric centers in New York. New York has a wealth of pediatric GI practices, which is great for the city. But it did mean that to get a very good standpoint, we wanted to capture a couple different other centers. We were able to get collaborators at NYU, Maimonides Medical Center, and Montefiore Medical Center in the Bronx, which gave us pretty good coverage of almost every borough.

And looking at that gives us a sort of picture that covers a lot of the city and let's just make sure that this is not a regional phenomenon or something specific to a specific patient population. We went back a certain window before the pandemic and then for the timeframe afterwards and collected just new diagnoses. So we looked at every set of new diagnoses so we could then do analyses, targeted, seeing did the pandemic, the presence of the pandemic and the MPI. Because it's not just that we're looking at COVID with the study, we're looking at everything around what happened, change the diagnostic rate. And we found some interesting things. But I'll let Dr. Rosenbaum talk a bit more about the design.

Dr Janet Rosenbaum:

So we had 3 institutions were able to give data dating back to 2011 and all 4 were able to give from 2016. And then we were able to go through June of 2022. So we had a good number and they submitted the month and year of diagnosis, the age at diagnosis, and just very basic demographics that allowed us to see whether there was a difference. We found that there was less illness by doing that comparison by what we would expect. And it was a random pattern. There was no real pattern prior to the pandemic. So it was just a question of were we inside the bounds of what we would expect? And sometimes it was inside the bounds, sometimes it was outside the bounds.

Dr Thomas Wallach:

I think the significance then, I think you may ask us some more things about that, is that we would expect if there was a key link and it was just all common viruses, that it would've dropped outside of the mountains. We'd see lower or lower than average. Pediatric IBD remains a relatively rare diagnosis. And so we're still talking about on the whole, 587 cases going back to 2016 and all the way through June of 2022—a number that well seems relatively large is also not that big considering you're talking about the 3 million pediatric patient population of New York City.

And so what we found that was interesting is while we were inside the bounds a lot, it was mostly on the higher side of the bounds. And so you can't say statistically that means something. But it was interesting. And then what was also notable is that there seemed to be windows about 4 to 6 months after peaks of the viral of COVID cases in New York City where we did see that that was where we exceeded the normal predicted bounds. We were finding that these things might be there an association. There's no way we can prove anything from what we did that COVID is causing the IBD cases. But it definitely raises a lot of smoke and suggests that there might be something we need to investigate more mechanistically.

Dr Janet Rosenbaum:

Just to answer the question of the number of participants, this was 351 in the prepandemic era and 236 during the pandemic. And in the prepandemic era there's a median of 13 Crohn's disease cases and during the pandemic there was a median of 16. And then for ulcerative colitis it was a median of 4 prepandemic and median of 6 during the pandemic. So it's suggestive, it's not clear cut. But this is one of the things where about a pilot study is that we have the pilot data and then to go and get actually the much larger national or even just fully citywide data may give a lot more clear results.

GLN:

Did you note, among those children who did present with IBD, which ones had actually contracted COVID-19 and which had not?

Dr Thomas Wallach:

So that was a significant hurdle and one that we were not really able to overcome, primarily just because the testing and the recording of those diagnoses early on in the pandemic, even for the first year, was extremely spotty. And then after that we faced the issue of then it got extremely good, but a lot of people were doing home testing. So a lot of folks who report, "I had COVID," did a home test during Omicron.

And so we have not had luck clearly delineating that because there is quite a bit of evidence that a lot of people had COVID that was never officially reported based on serology and other issues with things looking at that nature. So part of the issue is being able to identify that. And I think that's always going to be a challenge for anybody looking in the 2020 window because I don't think we're going to get that documentation.

Dr Janet Rosenbaum:

And I want to underscore that New York City had an extremely robust testing infrastructure. And so as much testing has happened in New York City, which there was a lot of, it didn't make it into the record.

Dr Thomas Wallach:

It's theoretically possible to obtain in the future, but it would require a bunch of different data access and not as simple as just going through one institution's health record.

GLN:

One thing I found interesting in your article is that you had found evidence of a trend toward the increased presentation of IBD among children that predated the pandemic. Could the rise in Crohn's cases, particularly among children that you saw after that first wave, simply be a reflection of that trend that was already taking place? Or did the children who were infected show an even higher rate of developing Crohn's? But of course, you can't answer that one for the reasons that we just discussed. But what do you think was driving that trend toward increased IBD, even before COVID?

Dr Thomas Wallach:

So broadly, that is a million-dollar question in IBD and in gastroenterology. Again, we don't know exactly the pathogenesis. We do know that there are variations that have a lot to do with the environment that you live in. We know that, for example, in the global south, Crohn's disease is extremely rare. Ulcerative colitis is much, much more rare than it is here, although not as rare as Crohn's. We know that those patterns persist in immigrant and first-generation populations, where the longer your family has lived here, the more your risk curve shifts from more likely to be UC to more likely to be Crohn's disease.

And we know that overall, the rates in the global north have been increasing, although not as quickly as they are in places that have modernized their healthcare infrastructure and sanitation infrastructure, for example, Singapore, Korea, coastal China, places like that. And so we've been sort of thinking recently that IBD, the raise has actually been tapering and that maybe we're seeing not as fast of an increase. I know in adult literature they definitely are seeing what they think might be a trend towards it not going up as quickly.

And so it is difficult for us to separate that out. And part of why we looked at the 5-year window before was to look at what the baseline trend was so that we could see what we would expect it to be in the future.

It's all very suggestive that there is a linkage between SARS-CoV-2 and the pathogenesis of IBD, but also that perhaps that is not a very specific finding and something that is more generalizable to inflammatory triggers like infections do actually drive this. And there's just a lot of different things that can create the same outcome, which is to say the formation of IBD. I'll let Dr. Rosenbaum talk.

Dr Janet Rosenbaum:

There's a question about what patient mix is going to each of these institutions that over a 5-year period does change as the neighborhoods around these areas change. But all of this is about looking at the aggregate of 4 institutions. And of course, with more institutions, there would be a little bit more smoothness about the specific patient composition, the patient mix would matter less. But we do see that there's more to begin with. Before the pandemic, there was a little bit more in the later part of our 5-year window before the pandemic. But it was even more than that during the pandemic and it was outside the bounds of what we would expect.

Dr Thomas Wallach:

Also interestingly, although not significant, we did see some things that would correlate with COVID exposure. We know from the city and state public health resources that the COVID burden was higher in Brooklyn and the Bronx than it was in Manhattan. And we saw more of a shift at those institutions than we saw at NYU, which is primarily based in Manhattan. Again, that was not significant. We can't really infer too much from that. But there's sort of secondary data points in what we've found in report that again, support the argument for further study and for the suggestion that the COVID in particular is prone to increasing risk of IBD formation. But requires a lot more mechanistic study to make anything besides an association there. This is just to say we're seeing a lot of smoke and maybe we should be looking at the fire.

GLN:

So are you involved in doing further evaluation of all this information, seeing if you can dig a little bit deeper and get to some of those answers or at least some perspective?

Dr. Thomas Wallach:

Yes. So we are currently looking at other data sources for sort of a larger version of this study, being able to look more comprehensively at regions or even nationwide. There are a couple great insurance-related data sets that are accessible that we are looking into. In peds IBD, there's something called ImproveCareNow, which is a national clearinghouse that reports a lot of things like diagnoses, severity, other issues like that. And so there's a couple different data points we're looking into.

I've done a little mechanistic work looking at the impact of persistent COVID infections on things like diseases of gut-brain interaction and other intestinal issues. And there has been some work done looking at the impact of COVID in IBD formation from a more metagenomic and epithelial behavior thing perspective. But we really would need to get a better idea, I think, of the epidemiology of this before we can really start to target clearly the ideal cases to look at from a mechanistic perspective.

And a big issue is there's so many different ways this could be contributing and we just don't understand the pathogenesis of IBD. Is this a shift in the metagenomic bacterial population of the gut? Is there some inflammatory cell, like long-term behavioral change, epidemic changes, epigenetic changes in how the epithelium is functioning or presenting antigens? You'd want to start picking high-likelihood patients and having an understanding of exactly what the epidemiology is and how that's shifted will give us, I think a better way to really look at this mechanistically, because mechanistic studies are intensive and expensive and you really want to know that what you're looking at is a problem that you need to find out how it works. Otherwise, you might spend a lot of money looking at something that is just mirrors your smoke.

GLN:

Okay. Any last thoughts that you would like to pass on to practicing gastroenterologists who are working with pediatric patients who may see an increase in the numbers of patients coming in who they suspect might have IBD, what would you say to them? What should they be looking for?

Dr. Thomas Wallach:

I think from a clinical perspective, what this tells me is that at least for the next little while, we will likely want to have a higher index of suspicion for IBD and to move a little faster towards endoscopic evaluation than you might have before, especially for patients with more mild symptoms, like failure to thrive or growth issues that you often see in Crohn's disease. Ulcerative colitis tends to buy its own ticket to endoscopy pretty quickly, but Crohn's disease is so much more subtle. I think the biggest practice shift is consider this a little bit more as a little bit more likely than perhaps you might've thought of before, even in a patient population that you wouldn't think of as being the highest risk for IBD. Because I think we are seeing this trend and talking to other providers in other places anecdotally, they are also reporting sort of similar effects. Obviously, additional study is necessary to say that they're really seeing that, but it does seem to be a fairly common experience.

Dr Janet Rosenbaum:

And on the policy side, the end of the public health emergency will bring an end to Medicaid coverage for some patients, and that has to be kept in mind. Currently, 95 million Americans are covered by Medicaid. And while children have greater eligibility than parents, it tends to be that when parents lose eligibility for Medicaid, their children will also be disenrolled because parents tend to have their child's healthcare follow their own. So that end has to be kept strongly in mind because that will pose a huge barrier to care is losing coverage.

GLN:

Thank you both very much. I'm very interested in finding out what happens next with your research. So I hope to speak with you again soon.