Last week, researchers from the National Institutes of Health’s RECOVER consortium had a major review paper about Long Covid in children published in the journal Pediatrics. The paper explores what researchers have learned about how this disease can impact children, including estimates of how many children may be impacted — up to 5.8 million in the U.S., according to their analysis — and details of common symptoms and co-diagnoses.
Betsy Ladyzhets spoke to Dr. Melissa Stockwell, a pediatrician and public health researcher at Columbia University and New York-Presbyterian Hospital who was one of the lead authors on the study and helps lead RECOVER’s pediatric research. She discussed what she hopes doctors reading this review paper will learn about Long Covid, as one of the paper’s key goals was to educate pediatricians who may be unfamiliar with the disease or may incorrectly think it doesn’t occur in children.
Dr. Stockwell also shared how she hopes RECOVER’s pediatric study will address ongoing questions about Long Covid in children. The pediatric observational study is set up similarly to RECOVER’s adult study, with thousands of patients participating at research sites across the country, but has a focus on following how Long Covid impacts kids of all ages. This study is also still recruiting new participants, she said.
This interview has been lightly edited and condensed for clarity.
Betsy Ladyzhets: How did you personally get involved with researching Long Covid in children?
Melissa Stockwell: My research originally had been on the use of technology to promote vaccination, like vaccination reminders. And then, as many in the vaccine world do, I segued into respiratory virus infection surveillance, which then turned into Covid research.
I got involved [with studying Long Covid in children] through the RECOVER initiative. They were looking to pull together sites. And here at Columbia, we really wanted to make sure that families like the ones we care for in Washington Heights and the Bronx would be represented in the Long Covid study. We proposed ideas, and then we got chosen to be one of the hubs, and we have a sub-site as well. (Editor’s note: “Hubs” within RECOVER refer to research centers that coordinate among different locations where patients are recruited.)
It’s been an amazing journey for me to learn about Long Covid, along with other researchers, and with the families. I think that’s a really important part about RECOVER, is how much the patient representatives and families participate.
BL: What would you want readers to know about the pediatric aspect of RECOVER?
MS: A lot of what we know about Long Covid really does come from adults, there’s much less that’s known about kids. And I think that pediatricians, for many of them, Long Covid isn’t really on their radar. That’s been hard for families who have talked to us in RECOVER: they know something’s wrong with their child, they go to the doctor, and at best, the doctor doesn’t know what they’re looking at and doesn’t know how to manage it. And at worst, the doctor doesn’t believe the family and the child…
Our hope is really to understand, how many kids are getting Long Covid? What are some of the factors that can put a child at risk for Long Covid? What are some resiliency factors? What are factors that can help improve recovery? The longitudinality is very important to us, so we can follow families and children over time and ask, who gets better and then relapses? I know from talking to families that [relapsing] is common. And then we need to understand what’s happening biologically in these kids as well.
We have a life course approach in taking care of kids. We have kids from zero up to age 25 in the pediatric, adolescent, and young adult cohort. Because we do think [Long Covid] may look different for a young kid, a school-aged kid, an adolescent, a young adult. Both symptoms and also what happens to that child, as they grow into the next stage? That’s a big concern for us as well, because we know how devastating this can be for children and their families. Even if, ultimately, medically, they get better, there’s always the fear, will they get worse again? And there’s this time that they’ve been really sick, often at very key developmental stages in their life, and how is that going to impact them?
BL: Right, and times in which kids might be missing school or missing out on other social experiences.
MS: As a pediatrician, the medical part is very hard to see, but it’s that academic and social piece that I worry about. Because there’s so much you’re supposed to do as a kid. You’re supposed to be in school and learning and be with your friends. If you miss out on that for a month, three months, six months, two years, or more — that whole child’s development is going to be affected. Even if they, hopefully, medically get better, and some unfortunately haven’t yet, even that period of time will have a profound impact on them.
BL: Changing gears a bit to the study, I wanted to ask, what was the motivation for doing this paper? Since it’s primarily a review of other research on Long Covid in kids?
MS: A number of RECOVER investigators were involved in this paper, the EHR [electronic health records] cohort and the pediatric observational cohort joined together. And the point of having this published in Pediatrics, or the journal of the American Academy of Pediatrics, is that it’s incredibly widely read. The AAP has a very large membership and, being a member, you get the journal.
We really felt, and have heard from patient representatives that are part of RECOVER, that pediatricians just don’t know about this [Long Covid in kids]. And so the point of the review is to say, “Look, there is this disease, maybe you’ve heard about it, you may not think that kids can get it, but they absolutely can and it can be devastating. And there are all of these different ways that it could manifest.” And we talk about RECOVER, because there’s a lot of unanswered questions that we’re hoping to answer. There’s been a fair amount of press on [the study], which is wonderful for us, because we really want to get this message out there. We feel like being part of RECOVER, we also have a mandate to teach people about Long Covid.
BL: That makes sense. What are some of the key things that you would want pediatricians to get out of reading the study?
MS: At the most basic, that kids can get Long Covid. And that some of the symptoms could have started during acute infection and then continued over time. Some symptoms are an underlying chronic condition that may get exacerbated during infection, and then those symptoms continue. And some symptoms — this is the hardest part — start afterwards. They could be a month, two months, three months, or longer after. And if you’re not making that connection, if a pediatrician is not saying, “You’re coming with fatigue, or post-exertional malaise,” and they’re not thinking about a Covid infection that happened two months, three months, six months ago… They’re not making that connection, and I really want them to make that connection.
The families sometimes are [making the connection between a Covid infection and new symptoms] and sometimes aren’t. This study is obviously for pediatricians, but maybe the media coverage will also bring this to families who aren’t aware of Long Covid. I want families to make that connection and talk to a pediatrician, and I want pediatricians to be able to say, “Yes, and here are some things that we can do to help get your child the care that they need.” That’s the key goal, recognizing Long Covid in children.
It’s also incredibly important that pediatricians are validating the experiences of children and their families. Say, a pediatrician sees a child with prolonged headaches, they should talk about it, try to understand it, try different treatments, maybe send them to a neurologist if that’s needed. Particularly talking about post-exertional malaise, don’t be saying to a family, “Oh, they just need to exercise more.” Which is incredibly detrimental. It’s the wrong thing to do physically, would set the child back, and also emotionally, because you’re making it sound like the kid can “exercise their way out of it,” which physiologically doesn’t make any sense.
[The paper discusses] how to recognize Long Covid, how to manage it, and how to get help for those kids. It can affect so many body systems, so that was part of the point of walking through all the body systems and symptoms. And there’s the piece about underlying conditions. For example, if someone had asthma, that can be exacerbated.
We wanted to end [the review] with RECOVER, because we feel like it is a very unique study with a large cohort across the lifespan, early childhood up to young adults. We hope to be able to answer questions in a way that other studies haven’t, because of the age groups, the longitudinality, tracking symptoms and also doing testing. And having input from patients and their families… Getting that perspective, I think that’s unique, at least in studies I’ve been a part of.
BL: Are there particular questions that you’re excited about RECOVER potentially answering? Or I know there’s biological testing involved, what do you consider to be some of the important pieces of that protocol?
ML: There’s a couple of things. First is understanding the symptoms — there’s so many possibilities, but what are the most common? I think that’s going to be helpful to families and pediatricians too. And the risk factors part, both clinical risk factors and social determinants of health — families want to know and understand that.
Trying to understand the pathophysiology behind it and understand the mechanisms is also important. We don’t know how they might be different in kids. Because children are sick at critical periods of childhood and development, even if mechanisms may start similarly [at different life stages], the impact may be different. Physically, if you start with a child who is tiny, 10 pounds, and then by the time they’re 19 they are 140 pounds, there’s huge brain growth and organ system growth — there’s so much happening, that really understanding that in children is going to be tough.
[RECOVER is] a starting point, there’s still going to be other questions that need to be addressed. Looking at the longitudinal part, like what happens to kids over time? A lot of families are asking, what is the trajectory? Like, “Will my child get better? Will they relapse?” … We don’t know answers to that yet.
For some families, just being in the study has been helpful. They want to be part of the research, part of answering those questions. I think it’s actually pretty profound for the kids as well, just to be able to have some agency. You lose a lot of agency over your body when you’re chronically ill, but [the study] is something they can choose to be part of. So that’s an added benefit of participating.
BL: That’s such a great point about the mechanism, I hadn’t thought about that. But I can see how something like viral persistence, which I know is one of the key mechanism hypotheses, could be very different if it’s happening while a kid is growing.
MS: That’s the question, right? Every time you answer a question, you find more questions, and we have more questions than answers. But that’s the exciting part of [this research] too, we really feel like we can make a difference.
BL: I know a big part of the study, as you mentioned, is trying to identify prevalence a bit more specifically. The paper discusses how estimates can be wildly different based on how many kids are in a given study and things like that. So I’m curious, both how you address that in this paper and how you hope the ongoing RECOVER work will help to solidify this estimate? The 5.8 million number has been cited a lot [in the media], I think.
MS: As you said, the prevalence estimates vary widely. I think it’s because there’s lots of different ways to do these studies. There’s, taking kids who are infected and asking [about later symptoms], but not having a control population… When you go through all the potential symptoms, and consider asking any adolescent or child, “Do you have any of these?” they’re likely going to say yes, because a lot of kids frequently have things like nasal congestion. So it’s important to have an uninfected group to compare to, so you can understand the prevalence piece and track symptoms.
Other factors that can impact prevalence estimates are, if you’re looking at one symptom or multiple symptoms, if you’re looking at four weeks or three months, if you have a population you’re comparing against, how you’re defining Long Covid, if it’s a small sample size or multiple sites… There’s so many pieces to this, and I think that’s why estimates are so wide.
Putting everything together, we think it’s probably around 10 to 20% of kids will have prolonged symptoms after Covid. That doesn’t necessarily mean they’ll have symptoms forever. And the 5.8 million estimate comes from, if you think about how many Covid cases there are [in the U.S.], about 20% are in kids, and then we estimate 10 to 20%. We could also look at seroprevalence studies done by the CDC, and they estimate 96% of kids or 66 million kids have had Covid. Even if less than 10% of them [have experienced Long Covid], it’s still millions of children.
I just looked this up for a talk: The classification of a rare disease is less than 200,000 people affected. So that puts into context, if we talk about potentially millions of children [with Long Covid]. But this is not something people are talking about. So why aren’t we talking about Long Covid in children, when we know there’s a lot of kids out there who are affected? We think part of the reason is, are families seeking care? Are pediatricians making that connection? Do they think they can’t call it Long Covid, because there isn’t a specific definition — there’s no biomarker, there’s no checkbox for this yet. We think that [lack of awareness] contributes to Long Covid being undercounted in children.
BL: Yeah, I have looked at the CDC seroprevalence estimates as well, and it’s kind of not surprising when you know almost everybody has gotten Covid at this point. But it’s interesting to me too, with the lack of testing these days, what you mentioned about attributing symptoms to Covid — I think that’s getting harder and harder. Though I guess with RECOVER the cohort is mostly full at this point, so you don’t have to worry about that so much?
MS: We actually are still recruiting for RECOVER [for the pediatric, adolescent, young adult cohort]! Especially those who are uninfected, we’re still recruiting, because as you said it’s very hard to find kids who are uninfected. And we do want to enroll more children with Long Covid. We have sites all over the country, there are also sites that can do remote enrollment. (Editor’s note: Learn more about joining the RECOVER pediatric study here.)
We really are still open and really want to enroll more. And you don’t need a formal diagnosis [to join]. I think that’s a misperception. Because it’s very hard for kids to get a formal diagnosis. So if there are children who have had a Covid infection and prolonged symptoms, even if no doctor has called it Long Covid yet, we would love to be able to enroll those families.
BL: I knew the adult study had finished enrolling a while ago, so I’m glad to hear the pediatric one is still open.
MS: Yes, we’re still open. And this is a great time to join. We would love to enroll more families. Anywhere you are, we would love to be able to enroll you.
BL: I understand there’s been a lot of effort to make sure it’s a diverse cohort, which seems important given what you were talking about with social determinants of health potentially playing a role in risk.
MS: Absolutely. From the very beginning, it has been, across everybody involved in RECOVER, that diversity and inclusion has been incredibly important to everybody. We really want to be reflective of the children of the country. Particularly, if you’re just looking at those who seek care, you’re missing a huge portion of the families who either don’t have access to care or may not know about Long Covid. So we have a lot of community sites we’re recruiting from, medical centers, social media… Lots of ways we’re recruiting, really with an eye towards having a diverse cohort.
We’re doing a good job in the pediatric cohort. (Editor’s note: Dr. Stockwell presented some demographic data about this cohort at a RECOVER webinar last month, copied here, along with other updates on the pediatric study.)
As I mentioned, in the beginning, that’s how I came into RECOVER. As a pediatrician who cares for families in Washington Heights and the Bronx, we really wanted to make sure that the families that we care for are represented. And I know a lot of the investigators around the country felt the same way… We want to make sure that the communities that we care for and care so much about are represented. And the community groups that are part of RECOVER want the same thing. We can’t have a national study if we’re not being representative.
BL: There’s one other thing I wanted to ask about with RECOVER. I’ve reported on this program a lot, and one criticism that I’ve heard, particularly from the patient community, is that there’s a lot of focus on observational studies while people are really invested in clinical trials to find treatments. So I wanted to ask, just from your perspective, why is it important to be doing the observational research, particularly for pediatrics, where the information we have is kind of less clear? And are there ways in which you see this research informing, maybe, pediatric-specific clinical trials down the line?
MS: I think it’s a good question… Ultimately, there need to be pediatric trials, and I think [researchers in the] pediatric cohort have strongly felt we want to have pediatric trials. But to set up those trials, we need to understand, what’s the outcome that you’re looking at? What does it look like in kids? What’s your inclusion criteria? It shouldn’t be based on adults. We think [outcomes measures] will look different across all developmental stages. So yeah, we do think [the observational research] will provide critically important information that will ultimately make trials more robust in the future.
But yes, we want to get there, too. As pediatricians, we want to support families and ultimately have treatments that will make children better. We want nothing more than for children to get back to the life they’re supposed to be living… Get back to all the things that kids should be doing, and not struggling with Long Covid. For some kids, it might be mild symptoms that resolve, and for others, it can be truly debilitating for them and their families.
BL: Are there further papers or other next steps that folks can look forward to from the RECOVER pediatric cohort?
MS: We are excited to have the paper come out in Pediatrics. And I mentioned in that webinar, we’re working on our first paper sharing new understanding about Long Covid in kids… Hopefully, in the future, I can come back and tell you all about it. Again, it’s important that we analyze our data quickly and get it out there, because we do think this is an incredibly important topic. I think the interest in the Pediatrics paper just shows how much information is missing, the country doesn’t know about Long Covid in kids. So we must get that information out there. And there’s other papers in the pipeline that we hope will be submitted over this next year.
BL: Nice. Is there anything else I didn’t ask that you would want readers of The Sick Times to know?
MS: Just that we’re still recruiting for RECOVER. And we’re grateful to the patient community, families of children with Long Covid, who have trusted us to do this study, to enroll, and to be part of this. We all have the same common goal and are looking forward to hopefully getting the answers that can help everybody.
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