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Hi, I'm Doctor Buddy Creech, and I'm a pediatric infectious diseases physician here in Nashville, Tennessee. And today, we're gonna talk a little bit about the management of high-risk pediatric COVID-19 patients. Uh, thankfully, the pandemic is over. Uh, we're still living through the PTSD of all of that. But there's still work to be done. This is still a significant respiratory virus for many of our patients. And so today, what we're gonna talk about is how to stratify those kids that are in high-risk categories, how to prioritize their testing, and then what we have both for treatment as well as prevention of severe disease in these kids. Uh, to get started, let me just say I do have some potential conflicts of interest. I received grant funding from the NIH and from the CDC as well as from Pfizer vaccines for a C. difficile vaccine clinical trial. I serve on the data and safety monitoring boards for a, a couple of companies for two specific studies. And then I serve as a consultant to a variety of groups really for the purpose of developing new vaccines and new antibiotics and making sure that the ones we have are safe and effective. As we think about therapeutic decision-making for children with COVID, it's really important to recognize what choices we do have and where there are still medical gaps. So I thought I would do this through a case presentation. This is a 14-year-old patient with a history of type 1 diabetes mellitus and autism who presents to the emergency department with fever, cough, and increased work of breathing. The fever has been present for about 4 days and symptoms are starting to worsen. Her oxygen saturations are 93% on room air and the respiratory rate is 25%. So she's placed on nasal cannula oxygen, and she's admitted for observation. So a few questions. Is she at risk? Is she at high risk? Does she need antiviral therapy? And does she need any type of immunomodulation like the corticosteroids or some of the newer agents that we use for COVID? So let's start with, is she at high risk for complications? I think we can absolutely say that she is indeed. Type 1 diabetes increases her risk of COVID-19 severity by about 3 times. And the neurologic condition of autism also increases that. And people often ask, why would autism increase the risk of severe respiratory disease? Because we also see it with influenza. And we think this is in part due to some of the fine motor control needed to cough and to clear the lungs for some neurologic conditions. For some, it's uh a restriction in their ability to communicate effectively what their symptoms actually are. And so rather than relying on both uh the child telling us how they're feeling and us looking at them, we're really limited with the data that we take in, especially parents. Um, and so this is one of the reasons why neurologic disease just writ large is an example of a high-risk condition for respiratory viral infections. So, we would say, yes, she's at high risk for complications. So, because of her being at high risk, are, are, in addition to supportive care, which obviously we do for all patients, what treatments would be recommended? And here, I think we're gonna need to think about where we get these resources. Right now, we get these from the AAP Redbook, from the FDA and from CDC recommendations for treatment. So, let's talk about options first. There are two antiviral therapies that are available for the pediatric population, recognizing that malnupiravir is something that's recommended for children or for adults over 18. The first is normorevir or ritonavir. Um, the population for this currently is those who are 12 years of age and older. And who weigh at least 40 kg. So some of your highest-risk kids who maybe failure to thrive or have chronic GI issues, make sure you remember the 40 kg part there too. It's an oral drug. we treat for 5 days. And it's best used if it's used within 5 days of illness onset. Usually, we use fever as the start of that, um, but, but it depends on how the cadence of the disease has been. The second is Rimdesivir, which we can use down to 1 month of age and at least 3 kg. It's IV only. It's used for 3 days. And here we have a little bit more wiggle room. It's less than 7 days. And in part, it's because we recognize that there may still be a role for antiviral therapy going into that, into that first week of illness, where we start to see more inflammation being driven by the virus rather than just viral effect alone. In addition to the antiviral therapies that are available to us, what are the immunomodulatory options that we have? Uh, and I really wanna highlight three. The first is dexamethasone, which is readily available and readily used. Although we can substitute prednisone when we need to. Uh, we do this on a mgs per kilo basis, and we usually treat for about 5 to 10 days. We also have two inhibitors of upstream inflammation. One is barricinib, which is a, a Janus kinase inhibitor. The second is tosillizumab, which is an IL-6 inhibitor. Remember that IL-6 is a primary driver of things like CRP and is a primary immunomodulating uh uh cytokine, specifically a pro-inflammatory cytokine. And we typically only use these latter two drugs for severe disease or where the use of corticosteroids might be contraindicated, like in someone with really fragile glucose levels. So, when should we consider treatment? And let's start in the outpatient setting. Outpatient setting antiviral therapy or immunomodulator therapy is, is really limited to a couple of situations. First would be if you have moderate or severe immunocompromise, such as cancer, untreated HIV, chronic steroid use, or if there's an underlying condition that increases risk, if they're not up to date on their vaccination and they don't have a, a COVID infection in the previous 4 months. So that would be the either or of those. And, and if you have an age less than 1, Recognizing that those children are at slightly increased risk, or those greater than 12, um, if they have 2 or more underlying medical conditions, or if they have one or more conditions that's severe or, or poorly controlled, this is when we would consider antiviral therapy in the outpatient setting. In the inpatient setting, it's a little bit different. If there's a new or, or increased oxygen demand, recommendations are really based on the route of supplemental oxygen delivery. So, if it's nasal cannula, like the case vignet, then we would start rimdesivir. And if no improvement in 24 to 48 hours, we would add dexamethasone, recognizing that at that stage of the illness, antiviral therapy is probably more important than anti-inflammatory treatment. But if they're on high-flow nasal cannula or greater, then that's when we would start dexamethasone and rimdesivir. And certainly, if they're on mechanical ventilation, if they go on to develop more significant resuscitative needs, we start dexamethasone, and if there's no improvement, we would add bericitinib or tocilizumab. Um, so, these are really important, uh, aspects of care is that there's both an antiviral and an immunomodulator component to it. So what would be the summary of these treatment recommendations? It's to know, test and treat. So, first is to know who's at highest risk for COVID complications, less than 1 month of age, 2 or more comorbidities, 1 or more comorbidities that are poorly controlled or unstable right now. Certainly those who are immunocompromised. We need to be able to test for SARS-COVID-2 in the right clinical context. So this is fever, respiratory illness, sore throat as we've seen with the most recent variant. And then, how do we treat? Well, we treat using a risk-based approach. It's modified by current disease severity. We use antivirals, immunomodulators, or both as we need to. And those recommendations are from the AA AAP Redbook, which I would encourage you to keep bookmarked on your computer or in your office.