The race to understand long-COVID in children

Around ten percent of children and young people develop persistent symptoms after their initial COVID-19 infection. Dr David Warburton of Children’s Hospital Los Angeles explains how the US National Institutes of Health’s RECOVER COVID initiative could help to understand why these long-term effects happen, and what to do about them.

11 August 2022
6 min read
by Linda Geddes
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<article> <h1> <span>The race to understand long-COVID in children</span> </h1> <div><p>Around ten percent of children and young people develop persistent symptoms after their initial COVID-19 infection. Dr David Warburton of Children’s Hospital Los Angeles explains how the US National Institutes of Health’s RECOVER COVID initiative could help to understand why these long-term effects happen, and what to do about them.</p> </div> <ul> <li> <b>11 August 2022</b> </li> <li> <b class="me-2">by</b> <span> <a href="https://www.gavi.org/vaccineswork/authors/linda-geddes" hreflang="en">Linda Geddes</a> </span> </li> </ul> <div> <div> <div> <div> <div> <p> </p> <h3>How big a problem is Long COVID in children?</h3> <p>It’s a lot more common than you might think – somewhere around 10%, which is a huge number when you consider how many COVID infections there are. The typical story is the young woman who was captain of her athletics team and a grade A student, and now can‘t get off the couch. But there are other presentations, such as heart and lung complications. That is why at Children’s Hospital Los Angeles we are taking a team approach— the study is being led by experts in pulmonary medicine, cardiology and infectious diseases.</p> <blockquote> <h2>The question is, should we be trying to find one medicine – a magic bullet – that treats the underlying process, or should we be trying to find, maybe a series of medicines that intervene at different stages in the process, or in different processes?</h2> </blockquote> <p>The main difference between the adult situation and the child‘s situation is that with a child, you’re dealing with a person who is still developing, and needs schooling and socialisation. Being chronically ill is never a good thing for that. If you’ve got chronic exhaustion, it is very difficult. I’ve seen examples of kids having to be home-schooled, and then maybe getting back to their high school and having to be pushed around in a wheelchair to get to their classes and being exhausted by two o’clock in the afternoon.</p> <h3>Are the underlying causes of these symptoms likely to be similar in children and adults?</h3> <p>One of the things that the RECOVER COVID initiative is trying to do – particularly in the paediatric population – is to find out what the causes of these chronic impacts are, because we don’t know at this stage. We have some ideas and hypotheses: one popular one is persistence of the virus somewhere in the bodies of patients who have recovered from COVID. Another is that it’s some kind of chronic inflammatory disease that gets going and doesn’t resolve. And the third one is some genetic predisposition that means certain people don’t recover because they have this problem.</p> <h3>Have any treatment pathways been developed for children and adolescents with these persistent symptoms?</h3> <p>Another thing we’re trying to do in RECOVER COVID is to prioritise ideas for treatment across a very broad spectrum of interventions. At this point, almost nothing has been subjected to, or proven to work, in clinical trials.</p> <p>The question is, what are you trying to treat? Since we don’t understand the underlying process, medical indication – where the doctor tries to treat the underlying problem – is quite difficult. From the patient’s perspective, you want to get rid of the symptoms. So, if it’s chronic exhaustion, you want something that’s going to buck you up. It may be that there are existing treatments for some of these symptoms, but they may not work particularly well in the context of Long COVID. So, then the question is, should we be trying to find one medicine – a magic bullet – that treats the underlying process, or should we be trying to find, maybe a series of medicines that intervene at different stages in the process, or in different processes? It’s a really complicated issue.<strong> </strong></p> <h3><strong>Is there any national or international consensus on what should be done at this stage?</strong></h3> <p>Various national and international medical organisations are trying to come up with some guidelines for doctors. We’re all desperate to do something, but the first principle should be to do no harm. The classic example is hydroxychloroquine: that was touted as a sovereign remedy for COVID on the recommendation of the US President, but unfortunately it has some nasty side effects and it turns out it isn’t an effective intervention. Another example is steroids: we’ve used steroids for years, in many branches of medicine, and they’re pretty well understood. But when, how much, and what formulation you give, turns out to have different answers in COVID; steroids can be beneficial in some circumstances, and actually harmful in others.</p> <div> <h4>Have you read?</h4> <ul> <li><a href="https://www.gavi.org/vaccineswork/long-covid-affects-1-8-says-lancet-study">Long COVID affects 1 in 8, says Lancet study</a></li> <li><a href="https://www.gavi.org/vaccineswork/long-covid-no-treatment-options-its-little-wonder-people-are-seeking-unproven" title="Long COVID: with no treatment options, it’s little wonder people are seeking unproven therapies like ‘blood washing’">Long COVID: with no treatment options, it’s little wonder people are seeking unproven therapies like ‘blood washing’</a></li> <li><a href="https://www.gavi.org/vaccineswork/long-covid-and-workplace-what-employers-could-do-better" title="Long COVID and the workplace: What employers could do better">Long COVID and the workplace: What employers could do better</a></li> </ul> </div> <p>I am serving on a committee for RECOVER COVID where we are trying to prioritise different treatments, to advise the NIH on where they should spend money to do trials. This goes all the way from antivirals and repeat vaccination, steroids and biological drugs, to various types of non-invasive therapies such as vagal stimulation, psychotherapy, neuro-rehabilitation, and cardiac rehabilitation. For each of these treatments, we have to consider the safety profile, the available evidence, and the potential benefit-to-toxicity ratio. It is a massive task, which is proceeding as fast as we can go. However, we don’t want to recommend something as a sovereign remedy, that we then later find is actually harmful.</p> <h3>Tell me a bit more about the RECOVER COVID trial, and particularly the paediatric population that you’re trying to recruit. What are you trying to achieve?</h3> <p>Children’s Hospital Los Angeles is one of several paediatric hospitals aiming to enroll about 20,000 children and young adults, to be representative of the general population of the United States – including those suffering from Long COVID, those who have never had COVID, and everyone in between. It is important to catch everybody, because the effects of this virus do differ by race, social environment and gender.</p> <p>The aim is, first of all, to find the incidence of this disease, then to look at the mechanism by compiling data from blood tests and various behavioural and physiological tests. We also have a study examining the underlying genetic causes of susceptibility to this virus. And then, once we’ve figured out which medications we want to try – which make the best sense and are likely to have the highest impact – we can go back and do trials on those patients, to find out which medication actually works.</p> <h3>How long do you think it will take to identify what works, so doctors can make better recommendations for their patients?</h3> <p>At the present time, licensed physicians can recommend what they feel is appropriate within the scope of their practice.</p> <p>The NIH is trying to investigate this in a rational way, and that takes time. First of all, you’ve got to understand what is wrong, and then you’ve got to have the insight to do something that changes it. So, I’m sorry to say I don’t see there being a miracle cure anytime soon. That’s not to say we can’t improve our technical practices by looking at what we’re doing, and what has an effect. But I think progress will be iterative, unless someone comes along with something that none of us have thought of yet.</p> <hr> <table border="0" cellpadding="0" cellspacing="0"> <tbody> <tr> <td width="30%"><img alt="David Warburton" data-entity-type data-entity-uuid src="/sites/default/files/vaccineswork/2022/Thumbnail/David-Warburton_h2.jpg" loading="lazy"></td> <td width="13px"> </td> <td> <p><small><em><strong><a href="https://keck.usc.edu/faculty-search/david-warburton/">David Warburton, MD</a></strong></em>, is one of the Principal Investigators for the NIH Researching COVID to Enhance Recovery (RECOVER COVID) at Children’s Hospital Los Angeles and Professor of paediatrics at at the Keck School of Medicine of USC.</small></p> </td> </tr> </tbody> </table> </div> </div> </div> </div> </div> <p> <a target="_blank" rel="noopener noreferrer" href="https://www.gavi.org/vaccineswork/race-understand-long-covid-children">Original article</a> </p><p>This article was originally published on <a target="_blank" rel="noopener noreferrer" href="https://www.gavi.org/vaccineswork">VaccinesWork</a> </p><script>(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-M7H54VD');</script><noscript><iframe src="https://www.googletagmanager.com/ns.html?id=GTM-M7H54VD" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript></article>

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How big a problem is Long COVID in children?

It’s a lot more common than you might think – somewhere around 10%, which is a huge number when you consider how many COVID infections there are. The typical story is the young woman who was captain of her athletics team and a grade A student, and now can‘t get off the couch. But there are other presentations, such as heart and lung complications. That is why at Children’s Hospital Los Angeles we are taking a team approach— the study is being led by experts in pulmonary medicine, cardiology and infectious diseases.

The question is, should we be trying to find one medicine – a magic bullet – that treats the underlying process, or should we be trying to find, maybe a series of medicines that intervene at different stages in the process, or in different processes?

The main difference between the adult situation and the child‘s situation is that with a child, you’re dealing with a person who is still developing, and needs schooling and socialisation. Being chronically ill is never a good thing for that. If you’ve got chronic exhaustion, it is very difficult. I’ve seen examples of kids having to be home-schooled, and then maybe getting back to their high school and having to be pushed around in a wheelchair to get to their classes and being exhausted by two o’clock in the afternoon.

Are the underlying causes of these symptoms likely to be similar in children and adults?

One of the things that the RECOVER COVID initiative is trying to do – particularly in the paediatric population – is to find out what the causes of these chronic impacts are, because we don’t know at this stage. We have some ideas and hypotheses: one popular one is persistence of the virus somewhere in the bodies of patients who have recovered from COVID. Another is that it’s some kind of chronic inflammatory disease that gets going and doesn’t resolve. And the third one is some genetic predisposition that means certain people don’t recover because they have this problem.

Have any treatment pathways been developed for children and adolescents with these persistent symptoms?

Another thing we’re trying to do in RECOVER COVID is to prioritise ideas for treatment across a very broad spectrum of interventions. At this point, almost nothing has been subjected to, or proven to work, in clinical trials.

The question is, what are you trying to treat? Since we don’t understand the underlying process, medical indication – where the doctor tries to treat the underlying problem – is quite difficult. From the patient’s perspective, you want to get rid of the symptoms. So, if it’s chronic exhaustion, you want something that’s going to buck you up. It may be that there are existing treatments for some of these symptoms, but they may not work particularly well in the context of Long COVID. So, then the question is, should we be trying to find one medicine – a magic bullet – that treats the underlying process, or should we be trying to find, maybe a series of medicines that intervene at different stages in the process, or in different processes? It’s a really complicated issue.

Is there any national or international consensus on what should be done at this stage?

Various national and international medical organisations are trying to come up with some guidelines for doctors. We’re all desperate to do something, but the first principle should be to do no harm. The classic example is hydroxychloroquine: that was touted as a sovereign remedy for COVID on the recommendation of the US President, but unfortunately it has some nasty side effects and it turns out it isn’t an effective intervention. Another example is steroids: we’ve used steroids for years, in many branches of medicine, and they’re pretty well understood. But when, how much, and what formulation you give, turns out to have different answers in COVID; steroids can be beneficial in some circumstances, and actually harmful in others.

Have you read?

I am serving on a committee for RECOVER COVID where we are trying to prioritise different treatments, to advise the NIH on where they should spend money to do trials. This goes all the way from antivirals and repeat vaccination, steroids and biological drugs, to various types of non-invasive therapies such as vagal stimulation, psychotherapy, neuro-rehabilitation, and cardiac rehabilitation. For each of these treatments, we have to consider the safety profile, the available evidence, and the potential benefit-to-toxicity ratio. It is a massive task, which is proceeding as fast as we can go. However, we don’t want to recommend something as a sovereign remedy, that we then later find is actually harmful.

Tell me a bit more about the RECOVER COVID trial, and particularly the paediatric population that you’re trying to recruit. What are you trying to achieve?

Children’s Hospital Los Angeles is one of several paediatric hospitals aiming to enroll about 20,000 children and young adults, to be representative of the general population of the United States – including those suffering from Long COVID, those who have never had COVID, and everyone in between. It is important to catch everybody, because the effects of this virus do differ by race, social environment and gender.

The aim is, first of all, to find the incidence of this disease, then to look at the mechanism by compiling data from blood tests and various behavioural and physiological tests. We also have a study examining the underlying genetic causes of susceptibility to this virus. And then, once we’ve figured out which medications we want to try – which make the best sense and are likely to have the highest impact – we can go back and do trials on those patients, to find out which medication actually works.

How long do you think it will take to identify what works, so doctors can make better recommendations for their patients?

At the present time, licensed physicians can recommend what they feel is appropriate within the scope of their practice.

The NIH is trying to investigate this in a rational way, and that takes time. First of all, you’ve got to understand what is wrong, and then you’ve got to have the insight to do something that changes it. So, I’m sorry to say I don’t see there being a miracle cure anytime soon. That’s not to say we can’t improve our technical practices by looking at what we’re doing, and what has an effect. But I think progress will be iterative, unless someone comes along with something that none of us have thought of yet.

David Warburton, MD, is one of the Principal Investigators for the NIH Researching COVID to Enhance Recovery (RECOVER COVID) at Children’s Hospital Los Angeles and Professor of paediatrics at at the Keck School of Medicine of USC.