child health
NIH HEAL Initiative Meets People Where They Are
Posted on by Rebecca Baker, Ph.D., NIH Helping to End Addiction Long-term® (HEAL) Initiative
The opioid crisis continues to devastate communities across America. Dangerous synthetic opioids, like fentanyl, have flooded the illicit drug supply with terrible consequences. Tragically, based on our most-recent data, about 108,000 people in the U.S. die per year from overdoses of opioids or stimulants [1]. Although this complex public health challenge started from our inability to treat pain effectively, chronic pain remains a life-altering problem for 50 million Americans.
To match the size and complexity of the crisis, in 2018 NIH developed the NIH Helping to End Addiction Long-term® (HEAL) Initiative, an aggressive effort involving nearly all of its 27 institutes and centers. Through more than 1,000 research projects, including basic science, clinical testing of new and repurposed drugs, research with communities, and health equity research, HEAL is dedicated to building a new future built on hope.
In this future:
- A predictive tool used during a health visit personalizes treatment for back pain. The tool estimates the probability that a person will benefit from physical therapy, psychotherapy, or surgery.
- Visits to community health clinics and emergency departments serve as routine opportunities to prevent and treat opioid addiction.
- Qualified school staff and pediatricians screen all children for behavioral and other mental health conditions that increase risk for harmful developmental outcomes, including opioid misuse.
- Infants born exposed to opioids during a mother’s pregnancy receive high-quality care—setting them up for a healthy future.
Five years after getting started (and interrupted by a global pandemic), HEAL research is making progress toward achieving this vision. I’ll highlight three ways in which scientific solutions are meeting people where they are today.
A Window of Opportunity for Treatment in the Justice System
Sadly, jails and prisons are “ground zero” for the nation’s opioid crisis. Eighty-five percent of people who are incarcerated have a substance use disorder or a history of substance use. Our vision at HEAL is that every person in jail, prison, or a court-supervised program receives medical care, which includes effective opioid use disorder treatment.
Some research results already are in supporting this approach: A recent HEAL study learned that individuals who had received addiction treatment while in one Massachusetts jail were about 30 percent less likely to be arrested, arraigned, or incarcerated again compared with those incarcerated during the same time period in a neighboring jail that did not offer treatment [2]. Research from the HEAL-supported Justice Community Opioid Innovation Network also is exploring public perceptions about opioid addiction. One such survey showed that most U.S. adults see opioid use disorder as a treatable medical condition rather than as a criminal matter [3]. That’s hopeful news for the future.
A Personalized Treatment Plan for Chronic Back Pain
Half of American adults live with chronic back pain, a major contributor to opioid use. The HEAL-supported Back Pain Consortium (BACPAC) is creating a whole-system model for comprehensive testing of everything that contributes to chronic low back pain, from anxiety to tissue damage. It also includes comprehensive testing of promising pain-management approaches, including psychotherapy, antidepressants, or surgery.
Refining this whole-system model, which is nearing completion, includes finding computer-friendly ways to describe the relationship between the different elements of pain and treatment. That might include developing mathematical equations that describe the physical movements and connections of the vertebrae, discs, and tendons.
Or it might include an artificial intelligence technique called machine learning, in which a computer looks for patterns in existing data, such as electronic health records or medical images. In keeping with HEAL’s all-hands-on-deck approach, BACPAC also conducts clinical trials to test new (or repurposed) treatments and develop new technologies focused on back pain, like a “wearable muscle” to help support the back.
Harnessing Innovation from the Private Sector
The HEAL research portfolio spans basic science to health services research. That allows us to put many shots on goal that will need to be commercialized to help people. Through its research support of small businesses, HEAL funding offers a make-or-break opportunity to advance a great idea to the marketplace, providing a bridge to venture capital or other larger funding sources needed for commercialization.
This bridge also allows HEAL to invest directly in the heart of innovation. Currently, HEAL funds nearly 100 such companies across 20 states. While this is a relatively small portion of all HEAL research, it is science that will make a difference in our communities, and these researchers are passionate about what they do to build a better future.
A couple of current examples of this research passion include: delivery of controlled amounts of non-opioid pain medications after surgery using a naturally absorbable film or a bone glue; immersive virtual reality to help people with opioid use disorder visualize the consequences of certain personal choices; and mobile apps that support recovery, taking medications, or sensing an overdose.
In 2023, HEAL is making headway toward its mission to accelerate development of safe, non-addictive, and effective strategies to prevent and treat pain, opioid misuse, and overdose. We have 314 clinical trials underway and 41 submissions to the Food and Drug Administration to begin clinical testing of investigational new drugs or devices: That number has doubled in the last year. More than 100 projects alone are addressing back pain, and more than 200 projects are studying medications for opioid use disorder.
The nation’s opioid crisis is profoundly difficult and multifaceted—and it won’t be solved with any single approach. Our research is laser-focused on its vision of ending addiction long-term, including improving pain management and expanding access to underused, but highly effective, addiction medications. Every day, we imagine a better future for people with physical and emotional pain and communities that are hurting. Hundreds of researchers and community members across the country are working to achieve a future where people and communities have the tools they need to thrive.
References:
[1] Provisional drug overdose death counts. Ahmad FB, Cisewski JA, Rossen LM, Sutton P. National Center for Health Statistics. 2023.
[2] Recidivism and mortality after in-jail buprenorphine treatment for opioid use disorder. Evans EA, Wilson D, Friedmann PD. Drug Alcohol Depend. 2022 Feb 1;231:109254.
[3] Social stigma toward persons with opioid use disorder: Results from a nationally representative survey of U.S. adults. Taylor BG, Lamuda PA, Flanagan E, Watts E, Pollack H, Schneider J. Subst Use Misuse. 2021;56(12):1752-1764.
Links:
SAMHSA’s National Helpline (Substance Abuse and Mental Health Services Administration, Rockville, MD)
NIH Helping to End Addiction Long-term® (HEAL) Initiative
Video: The NIH HEAL Initiative–HEAL Is Hope
Justice Community Opioid Innovation Network (HEAL)
Back Pain Consortium Research Program (HEAL)
NIH HEAL Initiative 2023 Annual Report (HEAL)
Small Business Programs (HEAL)
Rebecca Baker (HEAL)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes, Centers, and Offices to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 28th in the series of NIH guest posts that will run until a new permanent NIH director is in place.
Tackling Complex Scientific Questions Requires a Team Approach
Posted on by Nora D. Volkow, M.D., National Institute on Drug Abuse
During the COVID-19 pandemic, we have seen unprecedented, rapid scientific collaboration, as experts around the world in discrete, previously disconnected fields, have found ways to collaborate to face a common cause. For example, physicists helped respiratory specialists understand how virus particles could spread in air, leading to improved mitigation strategies. Specialists in cardiovascular science, neuroscience, immunology, and other fields are now working together to understand and address Long COVID. Over the past two years, we have also seen remarkable international sharing of epidemiological data and information on effects of vaccines.
Science is increasingly a team activity, which is true for many fields, not just biomedicine. The professional diversity of research teams reflects the increased complexity of the questions science is called upon to answer. This is especially obvious in the study of the brain, which is the most complex system known to us.
The NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, with the goal of vastly enhancing neuroscience through new technologies, includes research teams with neuroscientists, engineers, mathematicians, physicists, data scientists, ethicists, and more. Nearly half (47 percent) of grant awards have multiple principal investigators.
Besides the BRAIN Initiative, other multi-institute NIH research projects are applying team science to complex research questions, such as those related to neurodevelopment, addiction, and pain. The Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, created a team-based research framework to advance promising pain therapeutics quickly to clinical testing.
In the Adolescent Brain Cognitive Development (ABCD) study, which is led by NIDA in close partnership with NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA), and other NIH institutes, 21 research centers are collecting behavioral, biospecimen, and neuroimaging data from 11,878 children from age 10 through their teens. Teams led by experts in adolescent psychiatry, developmental psychology, and pediatrics interview participants and their families. These experts then gather a battery of health metrics from psychological, cognitive, sociocultural, and physical assessments, including collection and analysis of various kinds of biospecimens (blood, saliva). Further, experts in biophysics gather information on the structure and function of participants’ brains every two years.
A similar study of young children in the first decade of life beginning with the prenatal period, the HEALthy Brain and Child Development (HBCD) study, supported by HEAL, NIDA, and several other NIH institutes and centers, is now underway at 25 research sites across the country. A range of scientific specialists, similar to that in the ABCD study, is involved in this effort. In this case, they are aided by experts in obstetric care and in infant neuroimaging.
For both of these studies, teams of data scientists validate and curate all the information generated and make it available to researchers across the world. This makes it possible to investigate complex questions such as human neurodevelopmental diversity and the effects of genes and social experiences and their relation to mental health. More than half of the publications using ABCD data have been authored by non-ABCD investigators taking advantage of the open-access format.
Yet, institutions that conduct and fund science—including NIH—have been slow to support and reward collaboration. Because authorship and funding are so important in tenure and promotion decisions at universities, for example, an individual’s contribution to larger, multi-investigator projects on which they may not be the grantee or lead author on a study publication may carry less weight.
For this reason, early-career scientists may be particularly reluctant to collaborate on team projects. Among the recommendations of a 2015 National Academies of Sciences, Engineering, and Medicine (NASEM) report, Enhancing the Effectiveness of Team Science, was that universities and other institutions should find effective ways to give credit for team-based work to assist promotion and tenure committees.
The strongest teams will be diverse in other respects, not just scientific expertise. Besides more actively fostering productive collaborations across disciplines, NIH is making a more concerted effort to promote racial equity and inclusivity in our research workforce, both through the NIH UNITE Initiative and through Institute-specific initiatives like NIDA’s Racial Equity Initiative.
To promote diversity, inclusivity, and accessibility in research, the BRAIN Initiative recently added a requirement in most of its funding opportunity announcements (FOAs) that has applicants include a Plan for Enhancing Diverse Perspectives (PEDP) in the proposed research. The PEDPs are evaluated and scored during the peer review as part of the holistic considerations used to inform funding decisions. These long-overdue measures will not only ensure that NIH-funded science is more diverse, but they are also important steps toward studying and addressing social determinants of health and the health disparities that exist for so many conditions.
Increasingly, scientific discovery is as much about exploring new connections between different kinds of researchers as it is about finding new relationships among different kinds of scientific databases. The challenges before us are great—ending the COVID pandemic, finding a solution to the addiction and overdose crisis, and so many others—and increased collaboration between scientists will give us the greatest chance to successfully overcome these challenges.
Links:
Nora Volkow’s Blog (National Institute on Drug Abuse/NIH)
Adolescent Brain Cognitive Development Study
Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
Racial Equity Initiative (NIDA)
Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 13th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.
Antibody Response Affects COVID-19 Outcomes in Kids and Adults
Posted on by Dr. Francis Collins
Doctors can’t reliably predict whether an adult newly diagnosed with COVID-19 will recover quickly or battle life-threatening complications. The same is true for children.
Thankfully, the vast majority of kids with COVID-19 don’t get sick or show only mild flu-like symptoms. But a small percentage develop a delayed, but extremely troubling, syndrome called multisystem inflammatory syndrome in children (MIS-C). This can cause severe inflammation of the heart, lungs, kidneys, brain, and other parts of the body, coming on weeks after recovering from COVID-19. Fortunately, most kids respond to treatment and make rapid recoveries.
COVID-19’s sometimes different effects on kids likely stem not from the severity of the infection itself, but from differences in the immune response or its aftermath. Additional support for this notion comes from a new study, published in the journal Nature Medicine, that compared immune responses among children and adults with COVID-19 [1]. The study shows that the antibody responses in kids and adults with mild COVID-19 are quite similar. However, the complications seen in kids with MIS-C and adults with severe COVID-19 appear to be driven by two distinctly different types of antibodies involved in different aspects of the immune response.
The new findings come from pediatric pulmonologist Lael Yonker, Massachusetts General Hospital (MGH) Cystic Fibrosis Center, Boston, and immunologist Galit Alter, the Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge. Yonker runs a biorepository that collects samples from kids with cystic fibrosis. When the pandemic began, she started collecting plasma samples from children with mild COVID-19. Then, when Yonker and others began to see children hospitalized with MIS-C, she collected some plasma samples from them, too.
Using these plasma samples as windows into a child’s immune response, the research teams of Yonker and Alter detailed antibodies generated in 17 kids with MIS-C and 25 kids with mild COVID-19. They also profiled antibody responses of 60 adults with COVID-19, including 26 with severe disease.
Comparing antibody profiles among the four different groups, the researchers had expected children’s antibody responses to look quite different from those in adults. But they were in for a surprise. Adults and kids with mild COVID-19 showed no notable differences in their antibody profiles. The differences only came into focus when they compared antibodies in kids with MIS-C to adults with severe COVID-19.
In kids who develop MIS-C after COVID-19, they saw high levels of long-lasting immunoglobulin G (IgG) antibodies, which normally help to control an acute infection. Those high levels of IgG antibodies weren’t seen in adults or in kids with mild COVID-19. The findings suggest that in kids with MIS-C, those antibodies may activate scavenging immune cells, called macrophages, to drive inflammation and more severe illness.
In adults with severe COVID-19, the pattern differed. Instead of high levels of IgG antibodies, adults showed increased levels of another type of antibody, called immunoglobulin A (IgA). These IgA antibodies apparently were interacting with immune cells called neutrophils, which in turn led to the release of cytokines. That’s notable because the release of too many cytokines can cause what’s known as a “cytokine storm,” a severe symptom of COVID-19 that’s associated with respiratory distress syndrome, multiple organ failure, and other life-threatening complications.
To understand how a single virus can cause such different outcomes, studies like this one help to tease out their underlying immune mechanisms. While more study is needed to understand the immune response over time in both kids and adults, the hope is that these findings and others will help put us on the right path to discover better ways to help protect people of all ages from the most severe complications of COVID-19.
Reference:
[1] Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Bartsch YC, Wang C, Zohar T, Fischinger S, Atyeo C, Burke JS, Kang J, Edlow AG, Fasano A, Baden LR, Nilles EJ, Woolley AE, Karlson EW, Hopke AR, Irimia D, Fischer ES, Ryan ET, Charles RC, Julg BD, Lauffenburger DA, Yonker LM, Alter G. Nat Med. 2021 Feb 12.
Links:
COVID-19 Research (NIH)
“NIH effort seeks to understand MIS-C, range of SARS-CoV-2 effects on children,” NIH news release, March 2, 2021.
Lael Yonker (Massachusetts General Hospital, Boston)
Alter Lab (Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute
Building Resilience During the COVID-19 Pandemic
Posted on by Dr. Francis Collins
Dating back to our earliest times, humankind has experienced the psychological impact of a wide range of catastrophes, including famines, floods, earthquakes, wildfires, windstorms, wars, and, last but certainly not least, outbreaks of potentially deadly infectious diseases. We are certainly no exception today as people try to figure out how to cope—and help others cope—with the grief, stress, and anxiety caused by biggest health challenge of our time: the coronavirus 2019 (COVID-19) pandemic.
With more than 215,000 Americans having lost their lives and more than 7.8 million infected since COVID-19 first gripped our nation, the pandemic has taken a profound psychological and emotional toll on us all. Still, behavioral and social science researchers have identified some strategies to help us deal with our fears, and even rise to the challenge of supporting others during this unprecedented time.
Recently, I had an opportunity to discuss the science behind mental health responses to disasters with Dr. George Everly Jr., a psychologist and professor at the Johns Hopkins University Bloomberg School of Public Health, Baltimore. A world-renowned expert with more than 40 years experience studying the psychological impacts of disasters, he co-founded the International Critical Incident Stress Foundation, an organization affiliated with the United Nations. Our conversation took place via videoconferencing from our home offices in Maryland. Here’s a condensed transcript of our chat:
Collins: Good morning! At NIH, we are doing everything we can to keep our scientific mission going by supporting groundbreaking research into COVID-19 and a lot of other things. We’re also deeply committed to helping people manage stress and attend to mental health. So, we’ve invited Dr. Everly to share insights that I believe will help us learn some skills to build resilience. Goodness knows, this is a time where we all need resilience, as well as to help others around us. We’re all called upon, I think, to look after our friends and neighbors in the aftermath of a circumstance like the current pandemic.
Everly: It’s a privilege to spend some time with you today and chat about such an important topic. The topic we typically think about in terms of disasters is the physical response. Today, we’ll talk about the psychological impact of the COVID-19 pandemic. This is actually my third pandemic, having consulted in Hong Kong with SARS and Singapore with H1N1. I’ve also done consulting with Ebola.
However, I will tell you that this pandemic, COVID-19, has been the most challenging. I think we can we agree that mental health is an intrinsic value as it relates to us as humans. Anything that threatens mental health, especially in large numbers, threatens the core fabric of society.
According to the United Nations, we may now be looking at an impending international mental health crisis. Some have called this the “hidden” pandemic: people who previously coped well may have challenges and people who had challenges coping before COVID-19 may have increased challenges. Looking at first responders and frontline workers, we have seen heroic efforts on their part, but not without consequences—and mental exhaustion may be one of them
Collins: How is this crisis similar—and how is it different—from most of the disasters that people have dealt with?
Everly: The first thing is expectations. If we expected COVID-19 to be short lived, we have been remarkably, if not catastrophically, disappointed.
So, this connection occurred to me. A number of years ago, I was interested in the psychological impact of the London Blitz, and I went to England to interview people who went through that night upon night upon night of intractable bombing during World War II. I wanted to find out what helped people make it through. It was very clear that their initial belief that the bombing would be short-lived was tragically violated. They then as a community understood that they had to shift into a different mindset, and realize the Blitz wasn’t a sprint—it was marathon. They’d originally sent their children out into the countryside, but later decided to bring them back in the midst of bombing. I will suggest that psychologically, that was the turn of the war. In fact, research later by Anna Freud found that sending the kids away was psychologically more injurious than keeping them in the city. And I think that’s really important. Realizing that we are in for a long haul with COVID-19, in and of itself may be a game changer.
Collins: A very interesting comparison. I hadn’t thought about it that way—an acute disease becoming chronic.
Tell us a little bit more about the undercurrent of malaise in our country even before this COVID-19 pandemic hit—what economists Angus Deaton and Anne Case have recently written about as the “deaths of despair” and the opioid crisis. We are facing a pandemic from coronavirus, but it didn’t land on a completely blank page. It landed in a circumstance where many people were already feeling significant stress, and where depression was increasing risks of overdoses and suicide.
Everly: Fantastic question. You probably remember the work of Hans Selye, an endocrinologist who actually coined the term “stress.” He said, at any given point in time, we have a limited supply of what he called “adaptive energy.” In the best of conditions, this reservoir is quite high and will allow us to meet unusual challenges. However, I would suggest that the background noise of chronic issues that predated COVID-19 did begin to deplete that reservoir of adaptive energy, making us more vulnerable to things that turned out to be far more challenging than we thought. We were starting with one foot in the hole, so to speak.
Collins: All the more reason why our resilience is being called upon. Piled on top of it, many people are facing the serious challenge of trying to telework from home and trying to manage their responsibilities in terms of children or other family members who need care. My heart goes out to those folks as they struggle with this shared set of responsibilities, probably feeling as if there aren’t enough hours in the day and distractions are always getting in the way.
People are also feeling stressed now about the health of their children. What do we know—and what should we be thinking about—in terms of the mental health impact of the COVID-19 pandemic on kids?
Everly: In the spirit of full disclosure, I’m not a child psychologist. But I have studied trauma, crisis, and disaster for quite a while, and, invariably, children are part of that. One of the most powerful things I have seen in my career is that children often become reflections of their parents. Children not only desire, but they need, stability. My message to parents is that your children rely on you. You must be that strength for them. Even when you think you can’t be strong for yourself, reach down deep inside and say, “This isn’t just about you; it’s about others as well.”
I’ve got three young grandchildren, and this is the message I am telling their parents: “This is an important time. This may be one of the defining milestones in your children’s development. It’s an opportunity to show them how to cope.”
Collins: I have grandkids as well and have been watching how they have adapted. In some instances, I can see how they have actually gained in strength, as they’ve learned that this is an opportunity to face up to a challenge and learn how to cope. It does seem to be a mix of providing that foundation of support, but trying not to prevent children completely from having the experience of realizing they can get through some things themselves.
Everly: We can certainly be overprotective. From studying Olympic athletes, we learned that when they were asked what helped them reach the elite tier and win Olympic medals, they answered: challenge, plus adequate support. While well-intended, I think support alone is misdirected.
Collins: That makes sense. I know, during the current crisis, there is an interest in figuring out, in scientifically rigorous ways, what mental health interventions seem to produce good outcomes. Tell me a little bit more about where we stand as far as the opportunities to be doing these sorts of trials of various interventions. It would be a shame to go through this and then say to ourselves, “We missed a great opportunity there to learn more.”
Everly: It’s tough to do a randomized, controlled trial in the middle of a disaster. There are quite literally ethical issues at play. So, we approximate as best we can. For example, in the past, we built our own model of Psychological First Aid and tested it in two randomized controlled trials and three content validation studies, as well as in structural equation modeling studies. Have we tested it in this current environment? Not yet. There may be others doing that—I’m not sure.
If you take a look at the Cochrane Review on resiliency programs, you will perhaps be a little surprised. The review says there’s not a compelling body of evidence that resiliency programs work. However, we believe they work. We know there is this thing called human resilience and we encourage everyone to keep on trying to study it in scientifically rigorous ways.
Collins: I’m glad that you are. We should not miss the opportunity here to learn, because this is probably not our last pandemic—or our last crisis. Any final words?
Everly: So, with the caveat that I’m a diehard optimist …
Collins: That’s okay. I am too!
Everly: … I truly believe that from the greatest adversities, opportunities can emerge. When I spent three years in New York working after the 9/11 terrorist attack, I thought this is the defining moment, not just of my generation, but of others. I got to see it up close and personal, and worked intimately with various agencies. And I did see opportunities. As a result of 9/11, we changed not just the way we go through airports, but the way we look at trauma from a public health standpoint. Perhaps for the first time, we realized that we need to take a far more active preventative and interventional role.
Now, history repeats itself. I believe that this pandemic will change us for the rest of my life—and I don’t think all those changes need be negative. I think there are huge opportunities. I certainly am eager to investigate this at the highest levels of science. Let’s see why things work when they work and why things don’t work. Then, let’s use that information to build programs and test them in randomized, controlled trials.
I think we will come out of this pandemic better than we went into it. I would encourage people to understand that we’re in this together. Way back in the mid-1800s, Darwin told us that the greatest predictor of resilience was collaboration and cohesiveness. This is a time to reach out to each other.
Collins: I totally agree with that. You’re making a really good point: social distancing doesn’t have to mean anything more than physical distancing. We can stay socially close and reach out to each other in different ways.
We’re going to get through this, but get through it in a way that will change us. We will be changed by becoming stronger and more resilient, having learned some lessons about ourselves and about each other. We cannot simply hide our heads under our pillows and wait for this to pass. When you wake up in the morning, say to yourself: “I’m engaged in something that matters. I’m not just a passive victim of this terrible pandemic. I’m trying to do what I can and work toward getting us through.”
Many thanks, Professor Everly, for all your good work and for giving us this time to reflect on this important area of research and how to make the most of it.
Links:
Coronavirus (COVID-19) (NIH)
George S. Everly (Johns Hopkins University Bloomberg School of Public Health/Baltimore)
Video: Coping with the Mental Health Effects of COVID-19, George Everly with Francis Collins (NIH VideoCast)
The Power of Psychological First Aid. Dome. Minkove JF. March/April 2018. (Johns Hopkins Medicine/Baltimore)
Coping with Stress (Centers for Disease Control and Prevention)
Coping With Stress During Infectious Disease Outbreaks (Substance Abuse and Mental Health Services Administration)
National Suicide Prevention Lifeline
SAMHSA’s Disaster Distress Helpline, 1-800-985-5990
National Suicide Prevention Hotline, 1-800-273-TALK (8255); TTY number 1-800-799-4TTY (4889)
What We Know About COVID-19’s Effects on Child and Maternal Health
Posted on by Dr. Francis Collins
There’s been a lot of focus, and rightly so, on why older adults and adults with chronic disease appear to be at increased risk for coronavirus disease 2019 (COVID-19). Not nearly as much seems to be known about children and COVID-19.
For example, why does SARS-CoV-2, the novel coronavirus that causes COVID-19, seem to affect children differently than adults? What is the psychosocial impact of the pandemic on our youngsters? Are kids as infectious as adults?
A lot of interesting research in this area has been published recently. That includes the results of a large study in South Korea in which researchers traced the person-to-person spread of SARS-CoV-2 in the early days of the pandemic. The researchers found children younger than age 10 spread the virus to others much less often than adults do, though the risk is not zero. But children age 10 to 19 were found to be just as infectious as adults. That obviously has consequences for the current debate about opening the schools.
To get some science-based answers to these and other questions, I recently turned to one of the world’s leading child health researchers: Dr. Diana Bianchi, Director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Dr. Bianchi is a pediatrician with expertise in newborn medicine, neonatology, and reproductive genetics. Here’s a condensed transcript of our chat, which took place via videoconference, with Diana linking in from Boston and me from my home in Chevy Chase, MD:
Collins: What is the overall risk of children getting COVID-19? We initially heard they’re at very low risk. [NOTE: Since the recording of this interview, new data has emerged from state health departments that suggest that as much as 10 percent of new cases of COVID-19 occur in children.]
Bianchi: Biological factors certainly play some role. We know that the virus often enters the body via cells in the nasal passage. A recent study showed that, compared to adults, children’s nasal cells have less of the ACE2 receptor, which the virus attaches to and uses to infect cells. In children, the virus probably has less of an opportunity to grab onto cells and get into the upper respiratory tract.
Importantly, social reasons also play a role in that low percentage. Children have largely been socially isolated since March, when many schools shut down. By and large, young kids have been either home or playing in their backyards.
Collins: If kids do get infected with SARS-CoV-2, the virus that causes COVID-19, what kind of symptoms are displayed?
Bianchi: Children tend to be affected mildly. Relatively few children end up in intensive care units. The most common symptoms are: fever, in about 60 percent of children; cough; and a mild respiratory illness. It’s a different clinical presentation. Children seem to be more prone to vomiting, diarrhea, severe abdominal pain, and other gastrointestinal problems.
Collins: Are children as infectious as adults?
Bianchi: We suspect that older kids probably are. A recently published meta-analysis, or systematic review of the medical literature, also found about 20 percent of infected kids are asymptomatic. There are probably a lot of kids out there who can potentially infect others.
Collins: Do you see a path forward here for schools in the fall?
Bianchi: I think the key word is flexibility. We must remain flexible in the months ahead. Children have struggled from being out of school, and it’s not just the educational loss. It’s the whole support system, which includes the opportunity to exercise. It includes the opportunity to have teachers and school staff looking objectively at the kids to see if they are psychologically well.
The closing of schools has also exacerbated disparities. Schools provide meals for many kids in need, and some have had a lot of food insecurity for the past several months. Not to mention kids in homeless situations often don’t have access to the internet and other learning tools. So, on the whole, being in school is better for children than not being there. That’s how most pediatricians see it. However, we don’t want to put children at risk for getting sick.
Collins: Can you say a little bit more about the consequences, particularly for young children, of being away from their usual areas of social interaction? That’s true this summer as well. Camps that normally would be a place where lots of kids would congregate have either been cancelled or are being conducted in a very different way.
Bianchi: Thus far, most of the published information that we have has really been on the infection and the clinical presentations. Ultimately, I think there will be a lot of information about the behavioral and developmental consequences of not being exposed to other children. I think that older children are also really suffering from not having a daily structure, for example, through sports.
For younger children, they need to learn how to socialize. There are advantages to being with your parents. But there are a lot of social skills that need to be learned without them. People talk about the one-eyed babysitter, YouTube. The American Academy of Pediatrics has issued recommendations for limiting screen time. That’s gone out the window. I’ve talked with a lot of my staff members who are struggling with this balance between educating or entertaining their children and having so-called quality time, and the responsibility to do their jobs.
Collins: What about children with disabilities? Are they in a particularly vulnerable place?
Bianchi: Absolutely. Sadly, we don’t hear a lot about children with disabilities as a vulnerable population. Neither do we hear a lot about the consequences of them not receiving needed services. So many children with disabilities rely on people coming into their homes, whether it’s to help with respiratory care or to provide physical or speech therapy. Many of these home visits are on hold during the pandemic, and that can cause serious problems. For example, you can’t suction a trachea remotely. Of course, you can do speech therapy remotely, but that’s not ideal for two reasons. First, face-to-face interactions are still better, and, secondly, disparities can factor into the equation. Not all kids with disabilities have access to the internet or all the right equipment for online learning.
Collins: Tell me a little bit more about a rare form of consequences from COVID-19, this condition called MIS-C, Multi-System Inflammatory Syndrome of Children. I don’t think anybody knew anything about that until just a couple of months ago.
Bianchi: Even though there were published reports of children infected with SARS-CoV-2 in China in January, we didn’t hear until April about this serious new inflammatory condition. Interestingly, none of the children infected with SARS-CoV-2 in China or Japan are reported to have developed MIS-C. It seemed to be something that was on the European side, predominantly the United Kingdom, Italy, and France. And then, starting in April and May, it was seen in New York and the northeastern United States.
The reason it’s of concern is that many of these children are gravely ill. I mentioned that most children have a mild illness, but the 0.5 percent who get the MIS-C are seriously ill. Almost all require admission to the ICU. The scary thing is they can turn on a dime. They present with more of a prolonged fever. They can have very severe abdominal pain. In some cases, children have been thought to have appendicitis, but they don’t. They have serious cardiac issues and go into shock.
The good news is the majority survive. Many require ventilators and blood-pressure support. But they do respond to treatment. They tend to get out of the hospital in about a week. However, in two studies of MIS-C recently published in New England Journal of Medicine, six children died out of 300 children. So that’s what we want to avoid.
Collins: In terms of the cause, there’s something puzzling about MIS-C. It doesn’t seem to be a direct result of the viral infection. It seems to come on somewhat later, almost like there’s some autoimmune response.
Bianchi: Yes, that’s right. MIS-C does tend to occur, on an average, three to four weeks later. The NIH hosted a conference a couple weeks ago where the top immunologists in the world were talking about MIS-C, and everybody has their piece of the elephant in terms of a hypothesis. We don’t really know right now, but it does seem to be associated with some sort of exuberant, post-infectious inflammatory response.
Is it due to the fact that the virus is still hiding somewhere in the body? Is the body reacting to the virus with excessive production of antibodies? We don’t know. That will be determined, hopefully, within weeks or months.
Collins: And I know that your institute is taking a leading role in studying MIS-C.
Bianchi: Yes. Very shortly after the first cases of MIS-C were being described in the United States, you asked me and Gary Gibbons, director of NIH’s National Heart Lung and Blood Institute, to cochair a taskforce to develop a study designed to address MIS-C. Staff at both institutes have been working, in collaboration with NIH’s National Institute of Allergy and Infectious Diseases, to come up with the best possible way to approach this public health problem.
The study consists of a core group of kids who are in the hospital being treated for MIS-C. We’re obtaining biospecimens and are committed to a central platform and data-sharing. There’s an arm of the study that’s looking at long-term issues. These kids have transient coronary artery dilation. They have a myocarditis. They have markers of heart failure. What does that imply long-term for the function of their hearts?
We will also be working with several existing networks to identify markers suggesting that a certain child is at risk. Is it an underlying immune issue, or is it ethnic background? Is it this a European genomic variant? Exactly what should we be concerned about?
Collins: Let me touch on the genomics part of this for a minute, and that requires a brief description. The SARS-CoV-2 novel coronavirus is crowned in spiky proteins that attach to our cells before infecting them. These spike proteins are made of many amino acids, and their precise sequential order can sometimes shift in subtle ways.
Within that sequential order at amino acid 614, a shift has been discovered. The original Chinese isolate, called the D version, had aspartic acid there. It seems the virus that spread from Asia to the U.S. West Coast also has aspartic acid in that position. But the virus that traveled to Italy and then to the East Coast of the U.S. has a glycine there. It’s called the G version.
There’s been a lot of debate about whether this change really matters. More data are starting to appear suggesting that the G version may be more infectious than the D version, although I’ve seen no real evidence of any difference in severity between the two.
Of course, if the change turned out to be playing a role in MIS-C, you would expect not to have seen so many cases on the West Coast. Has anyone looked to see if kids with the D version of the virus ever get MIS-C?
Bianchi: It hasn’t been reported. You could say that maybe we don’t get all the information from China. But we do get it from Japan. In Japan, they’ve had the D version, and they haven’t had MIS-C.
Collins: Let’s talk about expectant mothers. What is the special impact of COVID-19 on them?
Bianchi: Recently, a lot of information has come out about pregnant women and the developing fetus. A recent report from the Centers for Disease Control and Prevention suggested that pregnant women are at a greatly increased risk of hospitalization. However, the report didn’t divide out hospitalizations that would be expected for delivering a baby from hospitalizations related to illness. But the report did show that pregnant women are at a higher risk of needing respiratory support and having serious illness, particularly if there is an underlying chronic condition, such as chronic lung disease, diabetes or hypertension.
Collins: Do we know the risk of the mother transmitting the coronavirus to the fetus?
Bianchi: What we know so far is the risk of transmission from mother to baby appears to be small. Now, that’s based on the fact that available studies seem to suggest that the ACE2 receptor that the virus uses to bind to our cells, is not expressed in third trimester placental tissue. That doesn’t mean it’s not expressed earlier in gestation. The placenta is so dynamic in terms of gene expression.
What we do know is there’s a lot of ACE2 expression in the blood vessels. An interesting recent study showed in the third trimester placenta, the blood vessels had taken a hit. There was actual blood vessel damage. There was evidence of decreased oxygenation in the placenta. We don’t know the long-term consequences for the baby, but the placentas did not look healthy.
Collins: I have a friend whose daughter recently was ready to deliver her baby. As part of preparing for labor, she had a COVID-19 test. To her surprise and dismay, she was positive, even though she had no symptoms. She went ahead with the delivery, but then the baby was separated from her for a time because of a concern about the mother transmitting the virus to her newborn. Is separation widely recommended?
Bianchi: I think most hospitals are softening on this. [NOTE: The American Academy of Pediatrics recently issued revised recommendations about labor and delivery, as well as about breastfeeding, during COVID-19]
In the beginning, hospitals took a hard line. For example, no support people were allowed into the delivery room. So, women were having more home deliveries, which are far more dangerous, or signing up to give birth at hospitals that allowed support people.
Now more hospitals are allowing a support person in the room during delivery. But, in general, they are recommending that the mother and the support person get tested. If they’re negative, everything’s fine. If the support person is positive, he or she’s not allowed to come in. If the mother is positive, the baby is separated, generally, for testing. In many hospitals, mothers are given the option of reuniting with the baby.
There’s also been a general discussion about mothers who test positive breastfeeding. The more conservative recommendation is to pump the milk and allow somebody else to bottle-feed the baby while the mother recovers from the infection. I should also mention a recent meta-analysis in the United Kingdom. It suggested that a cesarean section delivery is not needed because of SARS-CoV-2 positivity alone. It also found there’s no reason for SARS-CoV-2 positive women not to breast feed.
Collins: Well, Diana, thank you so much for sharing your knowledge. If there’s one thing you wanted parents to take away from this conversation, what would that be?
Bianchi: Well, I think it’s natural to be concerned during a pandemic. But I think parents should be generally reassuring to their children. We’ll get through this. However, I would also say that if a parent notices something unusual going on with a child—skin rashes, the so-called blue COVID toes, or a prolonged fever—don’t mess around. Get your child medical attention as soon as possible. Bad things can happen very quickly to children infected with this virus.
For the expectant parents, hopefully, their obstetricians are counseling them about the fact that they are at high risk. I think that women with chronic conditions really need to be proactive. If they’re not feeling well, they need to go to the emergency room. Again, things can happen quickly with this virus.
But the good news is the babies seem to do very well. There’s no evidence of birth defects so far, and very limited evidence, if at all, of vertical transmission. I think they can feel good about their babies. They need to pay attention to themselves.
Collins: Thank you, Diana, for ending on those wise words.
Bianchi: Thanks, Francis.
Links:
Coronavirus (COVID-19) (NIH)
Diana W. Bianchi, MD, Biosketch of the NICHD Director (Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH)
Responding to COVID-19, Director’s Corner, NICHD, June 3, 2020
National Child & Maternal Health Education Program (NICHD)
Pregnancy (NICHD)
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