Hi, good afternoon, my name is Steve Schein. I'm the Chief of Pediatric Critical Care at Rainbow Babies and Children's Hospital in Cleveland. And I'm going to be talking about pediatric COVID research consortiums. No financial disclosures, but I will share that myself and my colleagues do participate in some of these collaborations. So I'm going to presume that most of you guys are not pediatric intensivists and are adult providers. I will remind you that, yes, children also can get COVID-19 as well. And while the majority of our patients were relatively not super sick, we also did see our fair share of children required invasive ventilation, ECMO, and similar kind of life support technologies, both for acute COVID and for the multi-inflammatory system in children, or MISC. And just like our adult colleagues, we had a number of collaborations and consortiums come together over the pandemic to help us study this disease to learn how to best care for children that have COVID-19 and MISC. Some of these were very specific to COVID, like the Overcoming COVID Study. Some of them were offshoots of already established research networks, like the Pediatric Emergency Research Network. And we also had our own version of the Virus Registry, which, albeit, was a little bit smaller, both in terms of patient number and center number, than our adult partners and colleagues. And so my goal is to try to summarize some of the major work that came out of these collaboratives that was published in 2022. But I only have a short amount of time to do it, so apologies in advance that this does not include everything that was published in this year. But at least I wanted to kind of talk about some highlights and some themes that came out from these collaboratives. So one of the things that was well-described in both the virus group and also the US National COVID Cohort Collaborative was just the overall epidemiology and outcomes of children with acute COVID-19 and MISC who required high levels or ICU care. So in the virus study, in one of their reports, they had 400 children in the ICU, average age of 10, a slight male predominance. About half the children in that study had a comorbidity. In their study, almost half the kids had MISC, and about 15% were invasively ventilated. Somewhat similar findings in the US National COVID Cohort Collaborative, though they used a very different definition. They didn't use ICU admission, but what they called severe illness, which were things involving mechanical ventilation, vasoactives, ECMO, death, et cetera. They, again, found a similar age, similar slight male predominance. Again, about 40 to 50% of the kids having a comorbidity, though a much smaller prevalence of MISC and a much higher use of invasive ventilation, probably just due to their methodologic differences. In the virus study, they included non-ICU patients as well, finding that almost half the kids required ICU care and that that was statistically significantly associated with having MISC, with actually the absence of fever, which was kind of interesting. Having a seizure disorder and being older were all risk factors for ICU admission. And importantly, and keep this in the back of your mind, a 2% overall mortality from the study that at the time was predominantly from the United States. In the National Collaborative, they also looked at inpatients who didn't have severe disease, which is what they called moderate because mild was outpatient. And again, looked at the incidence of this severe disease, which was a little bit smaller, but with similar risk factors for it, including sex, race, and not surprisingly, having a comorbid condition. And again, a very low mortality rate, 1%. And obviously, this is from the United States, as you can see in the name. We can compare that to data that came from the United Kingdom, from the ICER group. Again, a smaller use of ICU than we saw in the States, but risk factors that looked very similar in terms of age, comorbidities, and also PEWS score, which is the Pediatric Early Warning Score, which is something that lots of hospitals use to help identify children at risk for decompensation based on their vitals and level of consciousness and things like that. Sort of like a Q sofa for kids. And again, a very low mortality rate. But there were also consortiums that were found in different parts of the world and places that might not have the same resources as the United States and the United Kingdom. So this comes from the AfriHealth Collaborative, which was six sub-Saharan African countries. You can see their general demographics there, including that 15% of their patients required ICU stay, but they had an 8% mortality, which I know for the adult people sounds very low, but like typical pediatric ICU mortality in tertiary and quaternary centers in the United States is like 1% to 2%, so 8% is pretty striking. One of the groups I was fortunate to participate in was the CAKE Study Investigators, or the Coronavirus and Kids Epidemiology. This is data that came from about a third from the United States and most of the rest from Latin America, and we found a 10% mortality rate associated with pre-existing risk factors like cardiac disease, pulmonary disease, et cetera. So it certainly seemed like the children cared for in less resource-intensive environments had a worse outcome, but a little bit of apples to apples in terms of study designs. So this was best actually evaluated by, again, a group of the ICEREC Collaborative, who intentionally designed this study to look at the differences in mortality between high-income countries and low- and middle-income countries, finding twice as high of a mortality rate in their univariate analysis, and then when they did an adjusted analysis to account for other factors, they did find that death was associated with younger age, and was strongly associated with being cared for in a lower- and middle-income country with an adjusted hazard ratio of almost five for mortality. Interestingly, they found a reduced rate of death with antivirals, which is a good transition to one of the other things that was well-described by Pediatric COVID Collaborations in 2022, which is the care that we provided for these children. In this observational study from the Overcoming COVID-19 Investigators, which was a CDC-funded study led by Adrian Randolph at Boston Children's, you can see just general sort of treatment patterns that are very even visually apparent over the course of 2020, with remdesivir and steroids being the most commonly used things, and obviously an increase in usage over time as we got more data, and while we dallyed in hydroxychloroquine in the very early days of the pandemic, that obviously went away pretty quick. In terms of whether or not these are actually associated with outcomes, this comes from the VIRUS study, and this is looking at combined therapy with IVIG and steroids for MIS-C versus IVIG alone, steroids alone, or neither, and they found that what they called Group A, which is the IVIG and steroid dual therapy group, was associated with a shorter length of stay in the ICU than kids who got neither of those treatments in the first two days. Now, both the Overcoming COVID study and also the BATS Consortium, which came out of the UK, had published similar data in 2021, looking at IVIG plus steroids versus IVIG alone, but they actually found conflicting results in the Overcoming COVID-19 study that was previously published. They found that dual therapy was associated with improved outcomes. They did not see an association in the BATS study. So these two collaboratives collaborated together to try to figure out why, and so they compared the patients that were in Overcoming COVID-19 versus those patients that were in the BATS study and found that the kids in the Overcoming COVID-19 study had a much higher utilization of the ICU and more vasoactives. So suggesting that maybe those were sicker patients, more likely to benefit, and that's why they saw those results in Overcoming COVID-19, which was similar to what they saw in virus, and virus similarly had a high use of ICU and a high use of vasoactives. So maybe it's just the sicker kids need the dual therapy. In terms of therapy beyond MIS-E, so for acute COVID-19, again, virus looked at that, and again, looking at steroids specifically, finding that a relatively small number of children were being treated acutely with steroids, and when they looked at outcomes, including ICU length of stay, they did not see an association between giving steroids early and either shortening or lengthening of the ICU length of stay, but they did find that care in a non-US center or being sicker at admission, not surprisingly, were associated with longer lengths of stay in the pediatric ICU. In terms of outcomes, and again, this comes from Overcoming COVID-19, so this is looking at long-term outcomes after acute COVID required hospitalizations, or the long COVID, but the pediatric version. They had about 150 children with acute COVID and 200 with MIS-E, 80% of them had follow-up data at two to four months, and in both conditions, more than 20% of patients still had symptoms two to four months after leaving the hospital, most commonly fatigue or weakness. When they also looked at activity impairment, again, finding 15 to 20% of children having issues two to four months, including not being able to walk or exercise as much as before. The Pediatric Emergency Research Network also pivoted and did some COVID work, too. So this is outcomes from children who were cared for in an emergency room. A large number of these kids were discharged home or just spent time in the inpatient ward, but not the ICU, and 6% overall had what they called a post-COVID condition, or a PCC, again, most commonly fatigue or weakness, and this was increasingly prevalent, depending on how sick the kid was. So more common in inpatients versus outpatients, more common in ICU patients than general ward patients. The PERN group also looked at the outcomes of children that were sent home in terms of how frequently they bounced back to the ER and needed to be admitted, finding that amongst the 2,500 children that were sent home with a diagnosis of COVID-19, only 2% of them required hospitalization in the next two weeks. So clearly, my colleagues and friends down in the PEDS ER are doing a pretty good job of knowing who to send home and who not, especially because the incidence of severe illness, sepsis, respiratory failure, et cetera, they only had 12 cases out of 2,500, so a pretty good job that they're doing down there. And finally, I'd be remiss if I didn't comment at least briefly on the vaccine work that all came out of the Overcoming COVID-19 study. So publishing in New England and in JAMA, they were able to show that vaccination reduces the risk of hospitalization in children, it reduces the risk of MIS-C, and it reduces the risk of ICU admission or the receipt of life support. So clearly, transformational work coming out of these pediatric COVID collaborations. So thank you to everyone who participated in these collaborations, and thank all of you guys for your time and attention.

pediatric COVID research consortiums

MIS-C

epidemiology

treatment patterns

vaccination impact