coronavirus and DNA

Case study: COVID-19 patient with autoimmune adrenal insufficiency and hypothyroidism

coronavirus and DNA

This is the first report of a pediatric patient with COVID-19 who developed autoimmune thyroid and cortisol deficiency, although not confirmed that it was related or triggered by the COVID-19 infection.

There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link has been established. In a case study, published in Hormone Research in Paediatrics, researchers at Children’s National Hospital report a 14-year-old girl admitted with COVID-19 and symptoms of MIS-C who was then recognized to have autoimmune polyglandular syndrome (APS2). This is the first report of a pediatric patient with COVID-19 who developed autoimmune thyroid and cortisol deficiency, although not confirmed that it was related or triggered by the COVID-19 infection.

What this means

APS2 is rare in children and has an incidence of 1 in 20,000. Until now, there have only been reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19.

“The role of COVID-19 in the etiopathogenesis of APS2 in this case remains unclear,” says Myrto Flokas, M.D., endocrinology fellow at Children’s National Hospital and first author of the case study. “But we suspect that it may have contributed to the rapid progression and severe clinical manifestations of both adrenal insufficiency and hypothyroidism leading to the presentation akin to MIS-C.”

The hold-up in the field

COVID-19 has been reported to affect the immune system and may serve as a trigger for autoimmune diseases similar to other viral infections.

“This is a case-report and while we cannot draw any mechanistic conclusions or infer causality, it is the first pediatric report of an association,” says Roopa Kanakatti Shankar, M.D., endocrinologist at Children’s National and one of the authors of the case study.  “We hope it will contribute to this novel field as our understanding of COVID-19 and its myriad effects on the immune system is still evolving.”

Why it matters

This case will alert clinicians to be mindful of the association and similarities in presentation of adrenal insufficiency to MIS-C and consider adrenal crisis in the differential diagnosis of such a presentation.

You can read the full case study, New-Onset Primary Adrenal Insufficiency and Autoimmune Hypothyroidism in a Pediatric Patient Presenting with MIS-C, in Hormone Research in Paediatrics.

pregnant woman

Early SARS-CoV-2 exposure may impact infant development

pregnant woman

The study found that some infants with in utero or early-life exposure to SARS-CoV-2 had borderline to low developmental screening scores.

Early SARS-CoV-2 exposure may impact neurodevelopment, especially among infants exposed in utero to symptomatic parents. This is according to a new study led by Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in the Prenatal Pediatrics Institute at Children’s National Hospital. Dr. Mulkey and team conclude that vaccination and other precautions to reduce early-in-life infection may protect against neurodevelopmental delays. Children with early SARS-CoV-2 exposure should have additional long-term screening for neurodevelopmental delays.

Children’s National Hospital leads the way

The developing brain is vulnerable to both direct and indirect effects of infection during pregnancy and in the early neonatal period. To chart the impact of this exposure, the team created a clinical follow-up protocol in the Congenital Infection Program at Children’s National to chart the development of 34 infants exposed to SARS-CoV-2 in utero or in the neonatal period.

What we hoped to discover

“We conducted this study because we know that infants, when exposed to maternal COVID-19 infection in utero can be exposed to inflammation, fever and an abnormal intrauterine environment. SARS-CoV-2 can also affect the placenta, and in turn, the developing brain,” Dr. Mulkey shared with Healio.

This study aimed to determine if infants with early SARS-CoV-2 exposure developed abnormal neurodevelopment in infancy and the factors that may impact neurodevelopment differences. The study found that some infants with in utero or early-life exposure to SARS-CoV-2 had borderline to low developmental screening scores, most common among babies born to mothers with symptomatic COVID-19. Researchers followed the infants in their first months of life, gauging how the exposure affected their neurologic development. Results were demonstrated using a screening test called the Ages & Stages Questionnaires (ASQ), and those whose scores were borderline or low were most often born to mothers with symptomatic COVID-19.

Why it matters

In conducting this study, the team found that babies born during the pandemic, specifically under these conditions, do, in fact, require additional follow-up in the early stages of life. We may also see more differences in developmental outcomes as children get older.

“Any measure we can take to help prevent infections for mothers in their pregnancy can improve long-term developmental outcomes for children,” says Dr. Mulkey.

Other members of the Children’s National team that contributed to this work include Roberta L. DeBiasi, M.D., M.S.; Meagan E. Williams, M.S.P.H.; Nadia Jadeed, R.N.C.; Anqing Zhang, Ph.D.; and Smitha Israel, B.S.N.

Dr. Mulkey also published a recent article in the American Journal of Obstetrics & Gynecology that found the COVID-19 vaccine may protect pregnant women from SARS-CoV-2 placentitis and stillbirth. This work builds upon Dr. Mulkey’s longitudinal studies on Zika virus infection in pregnancy and long-term impacts on the child, funded by the Thrasher Research Fund and the National Institutes of Health.

Sarah Mulkey

Exposure to Zika in utero may produce neurodevelopmental differences

Sarah Mulkey

“There are still many unanswered questions about the long-term impacts of Zika on children exposed in utero,” says Sarah Mulkey, M.D., Ph.D., a prenatal-neonatal neurologist in the Prenatal Pediatrics Institute at Children’s National Hospital.

Children who are exposed to the Zika virus while in the womb, but who are not subsequently diagnosed with Zika-related birth defects and congenital Zika syndrome (CZS), may still display differences in some aspects of cognitive development, mood and mobility compared to unexposed children, reports a study published in Pediatric Research. These findings suggest that Zika-exposed children may need some additional support and monitoring as they get older.

“There are still many unanswered questions about the long-term impacts of Zika on children exposed in utero,” says Sarah Mulkey, M.D., Ph.D., a prenatal-neonatal neurologist in the Prenatal Pediatrics Institute at Children’s National Hospital and the study’s first author. “These findings are another piece of the puzzle that provides insight into the long-term neurodevelopment of children with prenatal Zika virus exposure. Further evaluation is needed as these children get older.”

It has not been clear how children who were exposed to the Zika virus in the womb during the 2015–2017 epidemic, but who did not develop CZS and serious neurological complications, will develop as they get older.

Dr. Mulkey and colleagues examined the neurodevelopment of 55 children aged 3-5 years who were exposed to Zika in the womb in Sabanalarga, Colombia, and compared them to 70 control children aged 4-5 years who had not been exposed to Zika. Assessments occurred between December 2020 and February 2021. Health professionals tested the children’s motor skills (such as manual dexterity, aiming and catching, and balance) and their readiness for school (including knowledge of colors, letters, numbers and shapes). Parents completed three questionnaires providing information about their child’s cognitive function (such as memory and emotional control), behavioral and physical conditions (such as responsibility and mobility), and their parenting experience (including whether they felt distress).

Parents of Zika-exposed children reported significantly lower levels of mobility and responsibility compared to control children, although differences in cognitive function scores were not significant. Additionally, parents of 6 (11%) Zika-exposed children reported mood problems compared to 1 (1%) of control children, and Zika-exposed parents were significantly more likely to report parental distress.

Professional testing revealed no significant differences in the Zika-exposed children’s manual dexterity, such as their ability to catch an object or post a coin through a slot, compared to the control children. Both Zika-exposed and control children also scored lowly on readiness for school.

The authors highlight that parental responses may have been influenced by the Zika-exposed children’s parents’ perceptions or increased worry about the development of their child. Some differences in results may also have been caused by the age – and therefore developmental – differences between the groups of children.

The authors conclude that while these Zika-exposed children are making progress as they develop, they may need additional support as they prepare to start school.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

Staphylococcus aureus

Microbiological diagnoses and clinical outcomes for acute hematogenous osteomyelitis

Staphylococcus aureus

Acute hematogenous osteomyelitis is an infection that occurs in the bone and is most commonly caused by the pathogen Staphylococcus aureus.

Hospital length of stay (LOS) was shorter and odds of receiving three or more unique antibiotics for acute hematogenous osteomyelitis (AHO) was lower in culture-negative patients versus culture-positive patients, according to findings presented by researchers at Children’s National Hospital. The data was presented as part of a poster presentation at the ID Week 2022 conference.

AHO is an infection that occurs in the bone and is most commonly caused by the pathogen Staphylococcus aureus. AHO affects about 2-13 children per 100,000 in developed countries each year.

“For most patients with acute hematogenous osteomyelitis, the antibiotics we treat them with are empiric antibiotics – that is, our “best guess” at what antibiotic they should be on – as opposed to “definitive” antibiotics based on microbiologic results,” says Rana Hamdy, M.D., M.S.C.E., M.P.H., director of the Antimicrobial Stewardship Program at Children’s National Hospital and one of the authors of the study. “But with increasing antibiotic resistance, sometimes our “best guess” is wrong and that could lead to longer hospital length of stay and multiple changes in antibiotic regimens for some patients.”

She continues, “For this reason, the 2021 Pediatric Infectious Diseases Society clinical practice guidelines for patients with bone and joint infections suggest performing a bone biopsy when feasible to be able to have culture results to help guide the antibiotic choices.”

Blood and bone cultures may identify causative pathogens and determine antibiotic susceptibilities but obtaining bone cultures is an invasive procedure that carries risks including bleeding and the risk of sedation for the procedure.

The retrospective study included 367 patients under age 21 admitted to Children’s National Hospital from January 2010 – June 2020 with a final clinician’s diagnosis of AHO. Of the 367 patients, 210 (57.2%) had at least one positive culture result, 151 patients (41.1%) had all negative cultures, and 6 (1.6%) patients had no blood, bone or synovial fluid cultures obtained. About 83% of patients with positive culture were identified as having Staphylococcus aureus infections. Specifically, about 24% of identified pathogens were methicillin-resistant Staphylococcus aureus (MRSA).

In this population being culture-negative was associated with shorter LOS and lower odds of receiving three or more unique antibiotics.

“Our study disproved our hypothesis that patients without positive cultures would have longer hospital length of stay; however, because it was a retrospective study, there was the potential for additional confounding factors that we may not have been able to adjust for,” Dr. Hamdy adds.

HIV virus

CRISPR gene editing identifies possible drug targets for HIV

HIV virus

Working with researchers at Johns Hopkins University, the Children’s National team used CRISPR gene technology to test drug targets that find and attack latent HIV, paving the way for drug treatments that may someday completely cure the virus.

Researchers at Children’s National Hospital have identified several new drug targets that may enhance the elimination of latent HIV in patients, a major bottleneck to the full treatment of the virus, according to new findings published in Science Translational Medicine.

Working with researchers at Johns Hopkins University, the Children’s National team used CRISPR gene technology to test drug targets that find and attack latent HIV, paving the way for drug treatments that may someday completely cure the virus. Currently, anti-retroviral therapies (ARTs) can only slow its progress.

Why we’re excited

“In less than one month, we were able to use CRISPR to test 20,000 gene candidates in one single experiment. It was an amazing application of the technology,” said Wei Li, Ph.D., a co-author of the study and assistant professor at the Center for Genetic Medicine Research at Children’s National. “The CRISPR technology provides a global, unbiased approach to understanding molecular aspects of HIV-1 infection, including the ways that HIV-1 enters cells and replicates. This research could someday revolutionize how we treat the virus pharmaceutically.”

The big picture

More than 30 million people worldwide live with HIV-1, the most common form of the virus that can eventually lead to AIDS. But no single agent can entirely eliminate HIV-1 in these patients.

Researchers have sought ways to attack this elusiveness and turned to the CRISPR gene-editing tool, which can locate specific bits of DNA inside a cell. They trained CRISPR screens on the HIV-1 genome to identify critical factors that allow or prevent the virus from lying latent. In the latter case, these pieces of DNA will be the ideal targets of a drug that will push the virus out of the latent stage so it can be targeted by therapies.

What’s ahead

The findings of the Children’s National and Johns Hopkins scientists point to novel drug therapies and validation systems that could someday eradicate HIV.

Bicna Song, a postdoctoral researcher in Li’s laboratory at the Center for Genetic Medicine, said that reversing HIV-1 latency will allow for the killing of infected cells and give researchers opportunities to actually cure patients with HIV.

“So far, no single latency-reversing agent – alone or in combination with another drug – has been shown to effectively reduce the latent reservoir size in persons living with HIV-1,” said Song, who contributed to the study. “With this work, we are meeting the urgent need to identify factors that can lead to new drug targets.”

lung ct scan

With COVID-19, artificial intelligence performs well to study diseased lungs

lung ct scan

New research shows that artificial intelligence can be rapidly designed to study the lung images of COVID-19 patients.

Artificial intelligence can be rapidly designed to study the lung images of COVID-19 patients, opening the door to the development of platforms that can provide more timely and patient-specific medical interventions during outbreaks, according to research published this month in Medical Image Analysis.

The findings come as part of a global test of AI’s power, called the COVID-19 Lung CT Lesion Segmentation Challenge 2020. More than 2,000 international teams came together to train the power of machine learning and imaging on COVID-19, led by researchers at Children’s National Hospital, AI tech giant NVIDIA and the National Institutes of Health (NIH).

The bottom line

Many of the competing AI platforms were successfully trained to analyze lung lesions in COVID-19 patients and measure acute issues including lung thickening, effusions and other clinical findings. Ten leaders were named in the competition, which ran between November and December 2020. The datasets included patients with a range of ages and disease severity.

Yet work remains before AI could be implemented in a clinical setting. The AI models performed comparably to radiologists when analyzing data similar to what the algorithms had already encountered. However, the AI was less valuable when trained on fresh data from other sources during the testing phase, indicating that systems may need to study larger and more diverse data sets to meet their full potential. This is a challenge with AI that has been noted by others too.

What they’re saying

“These are the first steps in learning how we can quickly and accurately train AI for clinical use,” said Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, who led the Grand Challenge Initiative. “The global interest in COVID-19 gave us a groundbreaking opportunity to address a health crisis, and multidisciplinary teams can now focus that interest and energy on developing better tools and methods.”

Holger Roth, senior applied research scientist at NVIDIA, said the challenge gave researchers around the world a shared platform for developing and evaluating AI algorithms to quickly detect and quantify COVID lesions from lung CT images. “These models help researchers visualize and measure COVID-specific lesions of infected patients and can facilitate timelier and patient-specific medical interventions to better treat COVID,” he said.

Moving the field forward

The organizers see great potential for clinical use. In areas with limited resources, AI could help triage patients, guide the use of therapeutics or provide diagnoses when expensive testing is unavailable. AI-defined standardization in clinical trials could also uniformly measure the effects of the countermeasures used against the disease.

Linguraru and his colleagues recommend more challenges, like the lung segmentation challenge, to develop AI applications in biomedical spaces that can test the functionality of these platforms and harness their potential. Open-source AI algorithms and public curated data, such as those offered through the COVID-19 Lung CT Lesion Segmentation Challenge 2020, are valuable resources for the scientific and clinical communities to work together on advancing healthcare.

“The optimal treatment of COVID-19 and other diseases hinges on the ability of clinicians to understand disease throughout populations – in both adults and children,” Linguraru said. “We are making significant progress with AI, but we must walk before we can run.”

Dr. Limperopoulos talks to a mom

Pandemic-related stressors in pregnant women affect fetal brain development

Dr. Limperopoulos talks to a mom

Dr. Catherine Limperopoulos walking with a mom.

Prolonged levels of stress and depression during the COVID-19 pandemic contributed to altering key features of fetal brain development — even if the mother was not infected by the virus. This is what a study published in Communications Medicine suggests after following more than 200 pregnant women. The study, led by Children’s National Hospital experts, emphasized the need for more scientific inquiry to shed light on the long-term neurodevelopmental consequences of their findings and COVID-19 exposures on fetal brain development.

“Understanding how contemporary stressors may influence fetal brain development during pregnancy has major implications for basic science and informing public policy initiatives,” said Catherine Limperopoulos, Ph.D., chief and director of the Developing Brain Institute at Children’s National and senior author of the study. “With this work, we are able to show there’s a problem, it’s happening prenatally, and we can use this model to start exploring how we can reduce stress in moms and support unborn babies.”

To better understand the effects of environmental exposures on the fetus during pregnancy, further confirmation of the team’s latest findings is needed by ruling out other possibilities, such as maternal nutrition, financial security and genetic factors.

The psychosocial impact of COVID-19 on fetal brain development remains vastly understudied. The neurologic underpinnings of fetal development that turn into psycho-behavioral disorders later in life, including bipolar disorder, mood disorder or anxiety disorder, remain complex and difficult to explain.

Among the 202 participants from the Washington D.C. metropolitan area, 137 were part of the pre-pandemic cohort and 65 were part of the pandemic cohort.

Through advanced MRI imaging techniques and reconstruction of high-resolution 3D brain models, the researchers found a reduction of fetal white matter, hippocampal and cerebellar volumes and delayed brain gyrification in COVID-19 pandemic-era pregnancies. Validated maternal stress, anxiety and depression scales were also used to compare the scores between the two cohorts.

This study builds upon previous work from the Developing Brain Institute led by Limperopoulos, which discovered that anxiety in pregnant women appears to affect the brain development of their babies. Her team also found that maternal mental health, even in high socioeconomic status, alters the structure and biochemistry of the developing fetal brain, emphasizing the importance of mental health support for pregnant women.

“We’re looking at modifiable conditions,” said Limperopoulos. “What’s clear is the next frontier is intervening early to see how we can prevent or reduce stress in the mom’s current setting.”

pregnant hispanic woman

COVID-19’s impact on pregnant women and their babies

pregnant hispanic woman

While pregnant women are at higher risk of severe illness, coronavirus can also trigger inflammatory and vascular responses in the placenta during critical periods of fetal development in symptomatic and asymptomatic cases.

Pregnant women should get vaccinated to minimize the detrimental health effects COVID-19 has on the placenta, the fetus and the newborn, states Roberta L. DeBiasi, M.D., M.S., division chief of Pediatric Infectious Diseases at Children’s National Hospital in an editorial published in The Journal of Infectious Diseases.

The editorial provides a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field. The safety and efficacy of vaccination of pregnant women are also addressed.

While pregnant women are at higher risk of severe illness, the virus can also trigger inflammatory and vascular responses in the placenta during critical periods of fetal development in symptomatic and asymptomatic cases.

In this piece, Dr. DeBiasi comments on two related studies published in the same issue, Guan et al. and Shook et al., demonstrating pathologic findings in women’s placentas who had COVID-19 during pregnancy. Guan et al. published a detailed analysis of a stillbirth resulting from the delta variant infection during the third trimester.

“The authors present a highly plausible mechanism of stillbirth, namely that the virus-induced proinflammatory state ultimately led to placental abruption,” said Dr. DeBiasi.

Shook et al. presented a case series of pregnant women infected with the delta variant associated with stillbirth in two cases and one with severe neonatal illness.

“Taking the studies together, it’s evident that if a pregnant woman gets COVID-19 they’re at an increased risk of severe infection,” says DeBiasi. “They’re also at increased risk of adverse pregnancy outcomes, due to effects on the placenta, which may vary with specific circulating variants.”

Previous studies have documented that the placenta may be detrimentally affected by SARS-CoV-2 infection of the mother. However, maternal comorbidities such as hypertension, preeclampsia and gestational diabetes could also contribute to these findings.

“Despite these previous studies, the precise mechanisms of placental injury are still not clear and require further evaluation,” says Dr. DeBiasi. “Future research should include appropriate controls to better discern nonspecific versus SARS-CoV-2 specific effects and mechanisms of injury.”

Even though these potential risks exist, the vaccination rate among pregnant women is low. Dr. DeBiasi writes that recent publications have demonstrated vaccine efficacy and safety during pregnancy through programs that tracked the use in pregnant women. This data supports that COVID-19 vaccine offers another layer of protection to pregnant women since infants are not yet eligible for vaccination despite the fact that the youngest infants and children are among the most at risk among children for hospitalization.

Drs. Katie Donnelly, Panagiotis Kratimenos, Rana Hamdy, Shayna Coburn and Brynn Marks

Five Children’s National Hospital faculty named to Society for Pediatric Research

Drs. Katie Donnelly, Panagiotis Kratimenos, Rana Hamdy, Shayna Coburn and Brynn Marks

The Society for Pediatric Research (SPR) announced five new members from Children’s National Hospital: Drs. Rana Hamdy, Panagiotis Kratimenos, Brynn Marks, Shayna Coburn and Katie Donnelly.

The Society for Pediatric Research (SPR) announced five new members from Children’s National Hospital. Established in 1929, SPR’s mission is to create a multi-disciplinary network of diverse researchers to improve child health.

Membership in SPR is a recognized honor in academic pediatrics. It requires nomination by academic peers and leaders as well as recognition of one’s role as an independent, productive child health researcher.

“I am so proud of our faculty and all that they have accomplished. I am thrilled that they have been recognized for their achievements,” said Beth A. Tarini, M.D., M.S., SPR president and associate director for the Center for Translational Research at Children’s National Hospital.

SPR 2021 active new members from Children’s National are:

    • Katie Donnelly, M.D., M.P.H., attending physician in the Emergency Department at Children’s National Hospital. She is the medical director for Safe Kids DC, an organization dedicated to preventing accidental injuries in children in Washington DC. Her personal research interest is in preventing firearm injuries in children and she is a member of Safer through Advocacy, Firearm Education and Research (SAFER), a multidisciplinary team dedicated to firearm injury prevention at Children’s National. She is also the medical director of the newly founded hospital-based violence intervention program at Children’s National and an associate professor of pediatrics and emergency medicine at The George Washington University.“To be recognized by my peers as a researcher with a significant contribution to our field is very validating. It also opens a world of potential collaborations with excellent scientists, which is very exciting!” said Dr. Donnelly. “I am grateful for the immense support offered to me by the Division of Emergency Medicine to complete the research I am passionate about, especially my mentor Monika Goyal.”
    • Panagiotis Kratimenos, M.D., Ph.D., newborn intensivist and neuroscientist at Children’s National. He studies mechanisms of brain injury in the neonate, intending to prevent its sequelae later in life. Dr. Kratimenos’ interest lies in identifying therapies to prevent or improve neurodevelopmental disabilities of sick newborns caused by prematurity and perinatal insults.“Being a member of SPR is a deep honor for me. SPR has always been a ‘mentorship home’ for me since I was a trainee and a member of the SPR junior section,” said Dr. Kratimenos. “A membership in the SPR allows us to access a very diverse, outstanding team of pediatric academicians and researchers who support the development of physician-scientists, honors excellence through prestigious grants and awards, and advocates for children at any level either locally, nationally, or internationally.”
    • Rana Hamdy, M.D., M.P.H., M.S.C.E., pediatric infectious diseases physician at Children’s National and Director of the Antimicrobial Stewardship Program. She is an assistant professor of pediatrics at George Washington University School of Medicine and Health Sciences. Her area of expertise focuses on the prevention and treatment of antimicrobial resistant infections and the promotion of good antimicrobial stewardship in inpatient and outpatient settings.“It’s an honor to be joining the Society for Pediatric Research and becoming part of this distinguished multidisciplinary network of pediatric researchers,” said Dr. Hamdy. “I look forward to the opportunity to meet and work with SPR members, make connections for future collaborations, as well as encourage trainees to pursue pediatric research through the opportunities that SPR offers.”
    • Shayna Coburn, Ph.D., director of Psychosocial Services in the Celiac Disease Program at Children’s National. She is a licensed psychologist specializing in coping and interpersonal relationships in chronic illness treatment, particularly for conditions involving specialized diets. She holds an appointment as assistant professor of psychiatry and behavioral sciences at The George Washington University School of Medicine and Health Sciences. Her work has focused on promoting effective doctor-patient communication, reducing healthcare disparities and supporting successful adherence across the developmental span of childhood and adolescence. She currently has a Career Development Award from National Institute of Diabetes and Digestive and Kidney Diseases to refine and test a group intervention designed to improve self-management and quality of life in teens with celiac disease.
      “I hope that my background as a psychologist researcher will help diversify SPR. As an SPR member, I hope to encourage more opportunities for training, awards, and other programs that would be inclusive of clinician researchers who may not hold a traditional medical degree,” said Dr. Coburn.
    • Brynn Marks, M.D., M.S.-H.P.Ed., endocrinologist at Children’s National. As a clinical and translational scientist her goal is to use unique personal experiences and training to optimize both patient and provider knowledge of and behaviors surrounding diabetes technologies thereby realizing the potential of diabetes technologies improve the lives and clinical outcomes of all people living with diabetes. Her experiences as a person living with Type 1 diabetes have undoubtedly shaped her clinical and research interests in diabetes management and medical education.
      “It is an honor to be accepted for membership in the Society for Pediatric Research,” said Dr. Marks.  “Being nominated and recognized by peers in this interprofessional pediatric research community will allow me networking and growth opportunities as I continue to advance my research career.”
Hyundai Hope on Wheels Logo

Oncologists receive Hyundai Hope on Wheels grants

Hyundai Hope on Wheels Logo

Keri Toner, M.D., and Hannah Kinoshita, M.D., both oncology researchers at Children’s National Hospital, were recently awarded Hyundai Hope on Wheels cancer research grants.

Dr. Toner, who is an attending physician in the Center for Cancer and Blood Disorders and the Center for Cancer and Immunology Research at Children’s National, received a $300,000 Hyundai Scholar Hope Grant that she will use to develop and functionally evaluate a novel T cell therapy which can be translated to the clinic for treatment of pediatric patients with acute myeloid leukemia (AML).

Currently, patients with relapsed AML have very poor outcomes and the success that T cell therapy has had in treating B-cell malignancies has not yet been achieved for AML. Dr. Toner’s goal is to try to overcome some of these barriers with a novel T cell therapy which combines both native and chimeric T cell receptors to target AML.

“There are currently critical barriers to the success of T cell therapies for the treatment of AML,” Dr. Toner explains. “Successful completion of this research would allow for translation of a novel CAR-TAA-T therapy to the clinic for the treatment of relapsed/refractory AML, which has very poor prognosis.”

Meanwhile, Dr. Kinoshita, a pediatric hematology oncology fellow at Children’s National, received a $200,000 Hyundai Young Investigator Grant. She will use the funds to evaluate the immunobiology of multi-antigen specific T cell therapy infused to patients to reduce the two most common causes of morbidity and mortality following hematopoietic stem cell transplant (HSCT) for malignant disease: relapse and infection.

The administration of multiantigen specific T cells targeting tumor and viral-associated antigens following stem cell transplant may serve to prolong remission of malignant disease and prevent and treat viral infections that can cause devastating disease in children. Dr. Kinoshita’s study will evaluate the anti-viral and anti-leukemia immune response in vivo following targeted T cell therapy.

“There have been incredible advancements in the field of pediatric oncology and bone marrow transplant over the past 20-30 years but there are still many areas in which we need to continue to improve,” Dr. Kinoshita says. “Our patients and their families go through so much to get into remission and it is devastating if they relapse or develop severe infectious complications. Adoptive immunotherapy is a promising tool in aiding to treat and prevent these complications, particularly for patients with high-risk hematologic malignancies.”

The Hyundai Scholar Hope Grants and the Hyundai Young Investigator Grants are competitive research grants that are peer-reviewed by the Hyundai Hope on Wheels Medical Advisory Committee, which is comprised of leading pediatric oncologists from children’s hospitals and research institutions nationwide. The grants are open to U.S.-based Children’s Oncology Group member institutions.

doctor taking blood sample from child

Study shows increase in diabetes cases during COVID-19 pandemic

doctor taking blood sample from child

A retrospective study found pediatric Type 1 diabetes cases rose 15.2% and Type 2 diabetes cases increased by 182% during the first year of the COVID-19 pandemic compared to the prior two years— affecting non-Hispanic Black youth the most.

While the effects of COVID-19 on diabetes-related outcomes are extensively studied in adults, data about the incidence and severity of presentation of pediatric new-onset Type 1 diabetes (T1D) and Type 2 diabetes (T2D) is limited. A new retrospective study of 737 youth diagnosed with diabetes at Children’s National Hospital between March 11, 2018 and March 10, 2021 found pediatric T1D cases rose 15.2% and T2D cases increased by 182% during the first year of the COVID-19 pandemic compared to the prior two years — affecting non-Hispanic Black youth the most.

The study, published in Hormone Research in Paediatrics, compared T1D and T2D cases during the first 12 months of the pandemic, between March 11, 2020 and March 10, 2021, to the same time in the previous two years. This increase in cases was accompanied by a nearly six-fold rise in diabetic ketoacidosis (DKA) and a 9.2% incidence of hyperosmolar DKA during the pandemic as compared to no cases in the two years prior.

“A better understanding of the impact of the COVID-19 pandemic is crucial for raising public awareness, shaping policy and guiding appropriate health screenings,” said Brynn Marks, M.D., M.S.H.P.Ed., endocrinologist at Children’s National and lead author of the study.

Children’s National provides clinical care to approximately 1,800 youth with T1D and 600 youth with T2D annually. In the two years before the pandemic, cases of T2D accounted for 25.1% of all newly diagnosed diabetes at Children’s National compared to 43.7% during the pandemic. Before the pandemic, females accounted for 59.6% of youth with new-onset T2D but 58.9% of new-onset T2D cases were among males during the pandemic.

The researchers noted that the rise in cases of T2D and severity of presentation of both T1D and T2D during the pandemic disproportionately impacted non-Hispanic Black youth (NHB). NHB youth accounted for 58% of cases of T2D pre-pandemic, which further increased to 77% during the pandemic. The findings also showed that cases of DKA among NHB youth newly diagnosed with T1D increased during the pandemic compared to the two years before (62.7% vs. 45.8%, p=0.02).  Before the pandemic, there was no significant difference in A1c at T1D diagnosis between racial and ethnic groups. However, during the pandemic, hemoglobin A1c levels were higher among NHB youth.

“Future studies are needed to understand the root cause of the disproportionate impact of the COVID-19 pandemic on non-Hispanic Black youth with newly diagnosed diabetes,” said Dr. Marks. “These outcomes during the pandemic will likely worsen pre-existing health care disparities among youth with diabetes.  In understanding the indirect effects of our response to the pandemic, we can better inform future emergency responses and develop strategies to improve outcomes for all youth living with diabetes.”

sick child in palliative care hospital bed

New study compares first and second wave of MIS-C

sick child in palliative care hospital bed

When comparing the first and second wave of patients diagnosed with multi-system inflammatory syndrome in children (MIS-C), the second wave patients had more severe illness, according to a new prospective cohort study at Children’s National Hospital in Washington, D.C.

When comparing the first and second wave of patients diagnosed with multi-system inflammatory syndrome in children (MIS-C), the second wave patients had more severe illness, according to a new prospective cohort study of 106 patients at Children’s National Hospital in Washington, D.C. The results, published in The Pediatric Infectious Disease Journal, show that despite increased severity in the second wave cohort, both cohorts had similarities in cardiac outcomes and length of stay. Researchers are still working to better understand the exact immunologic mechanisms that trigger MIS-C and the specific factors accounting for its rare occurrence.

“We’ve now seen three distinct waves of MIS-C since the beginning of the pandemic, each wave following national spikes in cases,” said Roberta DeBiasi, M.D., chief of the Division of Pediatric Infectious Diseases at Children’s National and co-author of the study. “Kids in the second wave cohort had potentially experienced intermittent and/or repeated exposures to the virus circulating in their communities. In turn, this may have served as repeated triggers for their immune system which created the more severe inflammatory response.”

In this new study, key demographic features Children’s National researchers previously identified held true across both waves – including the fact that Black and Latino children are significantly more affected than white children.  Of the 106 patients, 54% were Black and 39% were Hispanic. The authors also noted that 75% of the patients were otherwise healthy children with no underlying medical conditions.

“While we believe the most recent third wave associated with the delta variant surge is tapering off, the findings from the first two waves provide important baseline information and are highly relevant for clinicians across the country that are evaluating and treating kids with MIS-C,” said Dr. DeBiasi.

Children’s National has cared for more than 4,200 symptomatic patients with SAR-CoV-2 infection and more than 185 MIS-C patients since the pandemic began. The first wave of MIS-C patients were hospitalized between March 2020 and October 2020. Second wave patients were hospitalized between November 2020 and April 2021. Each wave came 4-6 weeks following periods of COVID-19 surges in the community.

In the study, researchers compared patient demographics, clinical features, laboratory results, radiographic images, therapies and outcomes. The second wave cohort had a higher proportion of children 15 years of age or older. Patients also presented more frequently with shortness of breath and required more advanced respiratory and inotropic support. Researchers also found that patients in the second wave were less likely to test positive for SARS-CoV-2 on a PCR test.

Dr. DeBiasi and her team hope to unlock even more insights as they now analyze data from the third wave associated with the delta variant, which currently appears to have affected less children than the previous two. Children’s National is also working in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) to study the long-term effects of MIS-C and COVID-19 on the pediatric population after recovery. This is among the largest and longest studies being conducted, and researchers are hopeful the findings will help improve treatment of COVID-19 and MIS-C in the pediatric population both nationally and around the world.

“Our timely established multidisciplinary MIS-C task force here at Children’s National allowed us to reduce the learning curve,” said Ashraf S. Harahsheh, M.D., F.A.A.P., F.A.C.C., director of Quality Outcomes in Cardiology and co-first author of the study. “Experience from other centers showed that immunotherapy was utilized more frequently in recent MIS-C cohorts leading to reduction in percentage of cardiac complications. On the other hand, and despite having increased illness severity in the second cohort, our approach with prompt immunotherapy helped stabilize the rate of cardiac complications.”

masked kids giving thumbs up in front of school bus

Pediatricians and public health officials should unite against controversial school masking bans

masked kids giving thumbs up in front of school bus

To keep in-person learning and protect students in schools, pediatricians and public health officials must advocate for evidence-based mitigation strategies that can reduce COVID-19 transmission — especially the Delta variant, which overwhelmed pediatric emergency rooms and hospitals, argued Yang et al. in a Perspective published in the journal Pediatrics.

To keep in-person learning and protect students in schools, pediatricians and public health officials must advocate for evidence-based mitigation strategies that can reduce COVID-19 transmission — especially the Delta variant, which overwhelmed pediatric emergency rooms and hospitals, argued Yang et al. in a Perspective published in the journal Pediatrics.

The authors propose that pediatricians and their associated institutions actively advocate for masking in schools and debunk myths and misinformation during well and sick visits. In addition, they encourage doctors to develop and disseminate behavioral strategies to support children’s compliance with masking based on individual abilities and needs. Finally, providers can partner with educators at the local, district, state and national levels to advocate for evidence-based masking policies.

“As pediatricians, it is our responsibility to advocate for universal masking to facilitate safe in-person schooling for all children,” said Sarah Schaffer DeRoo, M.D., pediatrician at Children’s National Hospital and co-author of the Perspective. “Children have readily adapted to masking during the pandemic and continuing this practice in schools is not a significant change from their recent experience.”

To date, nine states have enacted policies to prohibit school masking mandates, disregarding evidence that masking is a crucial COVID-19 preventive measure, Yang et al. wrote. The court overturned these mandates in four states out of the nine because they either exceeded the governor’s executive authority or did not comply with the law granting the executive order’s authority. In other instances, judges have only placed a temporary block.

“Despite politically charged rhetoric and headline-grabbing lawsuits, evidence shows that schools without mask mandates are more likely to have COVID-19 outbreaks,” said Y. Tony Yang, Sc.D., endowed professor of health policy and executive director of the Center for Health Policy and Media Engagement at the George Washington University, and lead author of the Perspective. “Pediatricians have generally commanded a heightened level of public trust, which suggests that pediatricians who make the case for policies that advance sound medical and public health science may have a greater chance than other advocates of generating the public and political will needed to make evidence-based policy ideas, such as school mask mandates, a reality.”

Some localities have found creative ways to circumvent state mask mandate bans by altering the school dress code to include face coverings and finding loopholes that do not apply to individual cities. Parents have also tried to challenge the policies in court, asserting that mask mandate bans violate federal anti-discrimination laws.

“Continued efforts are needed to ensure schools are able to promote reasonable, evidence-based strategies to promote the health of their students, teachers and communities, and we, as advocates for children, are obligated to emphatically support these efforts,” said Yang et al.

illustration of lungs with coronavirus inside

Study compares outcomes of SARS-CoV-2 versus other respiratory viruses

illustration of lungs with coronavirus inside

Until now, little was known about the incidence and virus-specific patient outcome of SARS-CoV-2 compared to common seasonal respiratory viruses in children — including respiratory syncytial virus (RSV), human parainfluenza (hPIV), human metapneumovirus (hMPV), respiratory adenovirus and human rhinovirus (hHRV) and respiratory enterovirus (rENT).

Common respiratory viral infections were associated with a higher proportion of inpatient admissions but were similar in intensive care unit (ICU) admissions and death rates in hospitalized pediatric patients when compared to SARS-CoV-2, according to Children’s National Hospital researchers that led a study published in Infection Control & Hospital Epidemiology.

Until now, little was known about the incidence and virus-specific patient outcome of SARS-CoV-2 compared to common seasonal respiratory viruses in children — including respiratory syncytial virus (RSV), human parainfluenza (hPIV), human metapneumovirus (hMPV), respiratory adenovirus and human rhinovirus (hHRV) and respiratory enterovirus (rENT).

The researchers also noted that there was an overall substantial decrease in seasonal respiratory viral infections, especially the severe forms that require hospitalization. They believe that this correlation might be associated with the adoption of COVID-19 public health mitigation efforts, which played a major role in the reduction of these viruses that often circulate in fall and winter. The retrospective cross-sectional cohort study analyzed over 55,000 patient admissions between Match 15 and December 31, 2020. The findings shed light on the incidences of eight common seasonal respiratory viral infections before and during the COVID-19 pandemic. It also compared patient outcomes associated with COVID-19 and these other viral infections among pediatric patients at Children’s National.

Xiaoyan Song, Ph.D., M.Sc., chief infection control officer at Children’s National, spoke to us about the study.

Q: Why is this important work?

A: This is the first study to date that has described and compared hospitalization rates, ICU admission rates and death associated with COVID-19, RSV, seasonal influenza, rhinovirus, enterovirus and other common respiratory viral infections in children in one study. Previously, studies have compared one or two viruses at a time. This study compared 8 viruses, including the most detected ones – COVID-19, RSV, seasonal flu, rhinovirus and enterovirus.

Q: How will this work benefit patients?

A: This study will inform patients, families and the public that preventative measures like masking, hand hygiene, avoiding crowds and avoiding people who are ill are good practices that work to protect children from getting COVID-19 but also from getting infected with RSV, influenza and other viruses. Any of these respiratory viruses could harm a patient to a point where the child may have to be hospitalized or receive ICU care.

You can read the full study published in Infection Control & Hospital Epidemiology.

RSV infected infant cells

$2.13M grant accelerates treatments for kids with Down syndrome experiencing respiratory viruses

RSV infected infant cells

Children’s National Hospital received a combined $2.13 million award from the National Institutes of Health’s (NIH) National Heart, Lung and Blood Institute to better understand the mechanisms of severe viral respiratory infections in patients with Down syndrome and to develop new diagnostic tools and innovative precision medicine approaches for this vulnerable population.

“We have a unique opportunity to discover novel targets that can treat severe viral respiratory infections, including SARS-CoV-2,” said Gustavo Nino, M.D., M.S.H.S., D’A.B.S.M., principal investigator in the Center for Genetic Medicine at Children’s National. “Part of the award will help us accelerate the development of these novel approaches to prevent severe respiratory infections caused by SARS-CoV-2 and other viruses like respiratory syncytial virus infection (RSV) in children and adults with Down syndrome.”

Lower respiratory tract infections are a leading cause of hospitalization and death in children with Down syndrome. Those children have a nine times higher risk for hospitalization and mortality due to respiratory viruses that cause lower respiratory tract infections.

Chromosome 21, which is an extra chromosome copy found in patients with Down syndrome, encodes four of the six known interferon receptors, leading to hyperactivation of interferon response in Down syndrome. With the central role of interferons focused on antiviral defense, it remains puzzling how interferon hyperactivation contributes to severe viral lower respiratory tract infections in children with Down syndrome. This is an area that the researchers will explore to better manage and treat viral lower respiratory tract infections in these patients, with the support of NIH’s INCLUDE initiative. INCLUDE provides institutions with grants to help clinical research and therapeutics to understand and diminish risk factors that influence the overall health, longevity, and quality of life for people with Down syndrome related to respiratory viruses.

“While many of the other studies focus on intellectual and other disabilities, we are exploring a novel viral respiratory infectious disease mechanism and are doing so by working directly with patients and patient-derived samples,” said Jyoti Jaiswal, M.Sc., Ph.D., senior investigator in the Center for Genetic Medicine Research at Children’s National.

Children with Down syndrome have historically been excluded in research related to airway antiviral immunity, which is a focus of this human-based transformative study to improve the health and survival of patients with Down syndrome. There is a critical need for studies that define targetable molecular and cellular mechanisms to address dysregulated antiviral responses in this patient population.

“The clinical expertise at Children’s National in studying Down syndrome and the work of our team in caring for these patients with respiratory and sleep disorders positions us well to pursue this work,” said Jaiswal. “This is further supplemented by our initial studies that have identified a novel mechanism of impaired airway antiviral responses in these patients.”

Congresswoman Eleanor Holmes Norton (D-DC) also celebrated Children’s National and its NIH research funding benefitting people with Down syndrome.

“I am pleased to congratulate Dr. Nino and staff on being the recipients of the National Heart, Lung, & Blood Institute grant. You were chosen from a competitive group of applicants and should be proud of this notable achievement,” said Norton in a letter. “By receiving this grant, you have demonstrated outstanding promise in your field. It is my hope that this grant will enable you to better the local and global community.”

coronavirus

One-half of MIS-C patients at a single center experienced heart complications

coronavirus

A single center study of patients with multisystem inflammatory disease in children (MIS-C) found that half of children diagnosed with MIS-C had a heart complication as part of the disease. The study collected and analyzed data from 39 cases of MIS-C at Children’s National Hospital in 2020. MIS-C is a pediatric disease that has been linked to SARS-CoV-2, the virus that causes COVID-19.

The study’s findings appear in the journal Cardiology of the Young. The authors aimed to describe the type and frequency of cardiac complications in children with MIS-C while also outlining the disease’s short-term progression. They also hoped to better understand the demographics, clinical and laboratory findings, as well as the therapeutic successes for children with cardiac complications from MIS-C.

“While half of all children at our hospital diagnosed with MIS-C did experience a cardiac complication, it’s important to note that almost all of them (84%) also fully recovered from that cardiac complication within 50 days of diagnosis,” says Ashraf Harahsheh, M.D., director of Quality Outcomes in Cardiology at Children’s National Hospital, who led the study. “We were also able to identify a few common factors among those with cardiac complications that, with further research, may help us identify earlier the children with MIS-C who are at greater risk for heart problems.”

The study found that children with cardiac complications had higher levels of natriuretic peptides, which appear in greater numbers when the heart isn’t pumping enough blood to the rest of the body. Additionally, children who developed heart complications also had higher initial white blood cell counts. MIS-C cardiac complications ranged from mild systolic dysfunction to coronary artery abnormalities and/or artery dilation.

This was a retrospective, observational study of 39 patients admitted to Children’s National Hospital from March 2020 to September 2020 who met the Centers for Disease Control and Prevention MIS-C case definition. Patient demographics, clinical features, laboratory values, diagnostic investigations, including echocardiograms, and therapies were extracted from the electronic medical records.

“This syndrome has some similarities to Kawasaki disease, another inflammatory syndrome that is known to cause cardiac complications,” says Dr. Harahsheh. “Thankfully what we’ve learned from studying and treating Kawasaki disease in children has helped us collaborate with partners around the world to find treatments for MIS-C that seem to minimize the impact of these complications, at least in the short term.”

coronavirus

Children’s National Hospital and NIAID launch large study on long-term impacts of COVID-19 and MIS-C on kids

coronavirus

Up to 2,000 children and young adults will be enrolled in a study from Children’s National Hospital in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) that will examine the long-term effects of COVID-19 and multisystem inflammatory syndrome in children (MIS-C) after these patients have recovered from a COVID-19 infection.

This $40 million multi-year study will provide important information about quality of life and social impact, in addition to a better understanding of the long-term physical impact of the virus, including effects on the heart and lung. The researchers hope to detail the role of genetics and the immune response to COVID-19, so-called “long COVID” and MIS-C, including the duration of immune responses from SARS-CoV-2, the virus that causes COVID-19. It is fully funded by a subcontract with the NIH-funded Frederick National Laboratory for Cancer Research operated by Leidos Biomedical Research, Inc.

“We don’t know the unique long-term impact of COVID-19 or MIS-C on children so this study will provide us with a critical missing piece of the puzzle,” says Roberta DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases at Children’s National and lead researcher for this study. “I am hopeful that the insights from this enormous effort will help us improve treatment of both COVID-19 and MIS-C in the pediatric population both nationally and around the world.”

Over the past year, more than 3.6 million children have tested positive for SARS-CoV-2 and over 2,800 cases of MIS-C have been reported throughout the U.S. While the vast majority of children with primary SARS-CoV-2 infection may have mild or no symptoms, some develop severe illness and may require hospitalization, including life support measures. In rare cases, some children who have previously been infected or exposed to someone with SARS-CoV-2 have developed MIS-C, a serious condition that may be associated with the virus. MIS-C symptoms can include fever, abdominal pain, bloodshot eyes, trouble breathing, rash, vomiting, diarrhea and neck pain, and can progress to shock with low blood pressure and insufficient cardiac function. Long COVID is a wide range of symptoms that can last or appear weeks or even months after being infected with the virus that causes COVID-19.

The study is designed to enroll at least 1,000 children and young adults under 21 years of age who have a confirmed history of symptomatic or asymptomatic SARS-CoV-2 infection or MIS-C. Participants who enroll within 12 weeks of an acute infection will attend study visits every three months for the first six months and then every six months for three years. Participants who enroll more than 12 weeks after acute infection will attend study visits every six months for three years. The study will also enroll up to 1,000 household contacts to serve as a control group, and up to 2,000 parents or guardians (one parent per participant) will complete targeted questionnaires.

“The large number of patients who will be enrolled in this study should provide us with a truly comprehensive understanding of how the virus may continue to impact some patients long after the infection has subsided,” says Dr. DeBiasi.

The study primarily aims to determine incidence and prevalence of, and risk factors for, certain long-term medical conditions among children who have MIS-C or a previous SARS-CoV-2 infection. The study will also evaluate the health-related quality of life and social impacts for participants and establish a biorepository that can be used to study the roles of host genetics, immune response and other possible factors influencing long-term outcomes.

Children’s National was one of the first U.S. institutions to report that children can become very ill from SARS-CoV-2 infection, despite early reports that children were not seriously impacted. In studies published in the Journal of Pediatrics in May of 2020 and June of 2021, Children’s National researchers found that about 25% of symptomatic COVID patients who sought care at our institution required hospitalization. Of those hospitalized, about 25% required life support measures, and the remaining 75% required standard hospitalization. Of patients with MIS-C, 52% were critically ill.

Study sites include Children’s National Hospital inpatient and outpatient clinics in the Washington, D.C. area, and the NIH Clinical Center in Bethesda, Maryland.

Those interested in participating should submit this form. You will then be contacted by a study team member to review the study details and determine whether you are eligible to participate.

You can find more information about the study here.

little boy at doctor

Demographic, clinical and biomarker features of MIS-C

little boy at doctor

In a new observational study, researchers provide insight into key features distinguishing MIS-C patients to provide a more realistic picture of the burden of disease in the pediatric population and aid with the early detection of disease and treatment for optimal outcomes.

Multisystem Inflammatory Syndrome in Children (MIS-C) significantly affected more Black and Latino children than white children, with Black children at the highest risk, according to a new observational study of 124 pediatric patients treated at Children’s National Hospital in Washington, D.C. Researchers also found cardiac complications, including systolic myocardial dysfunction and valvular regurgitation, were more common in MIS-C patients who were critically ill. Of the 124 patients, 63 were ultimately diagnosed with MIS-C and were compared with 61 patients deemed controls who presented with similar symptoms but ultimately had an alternative diagnosis.

In the study, published in The Journal of Pediatrics, researchers provide insight into key features distinguishing MIS-C patients to provide a more realistic picture of the burden of disease in the pediatric population and aid with the early detection of disease and treatment for optimal outcomes. The COVID-linked syndrome has affected nearly 4,000 children in the United States in the past year. Early reports showed severe illness, substantial variation in treatment and mortality associated with MIS-C. However, this study demonstrated that with early recognition and standardized treatment, short-term mortality can be nearly eliminated.

“Data like this will be critical for the development of clinical trials around the long-term implications of MIS-C,” says Dr. Roberta DeBiasi, M.D., lead author and chief of the Division of Pediatric Infectious Diseases at Children’s National. “Our study sheds light on the demographic, clinical and biomarker features of this disease, as well as viral load and viral sequencing.”

Of the 63 children with MIS-C, 52% were critically ill, and additional subtypes of MIS-C were identified including those with and without still detectable virus, those with and without features meeting criteria for Kawasaki Disease, and those with and without detectable cardiac abnormalities. While median age (7.25 years) and sex were similar between the MIS-C cohort and control group, Black (46%) and Latino (35%) children were overrepresented in the MIS-C group, especially those who required critical care. Heart complications were also more frequent in children who became critically ill with MIS-C (55% vs. 28%). Findings also showed MIS-C patients demonstrated a distinct cytokine signature, with significantly higher levels of certain cytokines than those of controls. This may help in the understanding of what drives the disease and which potential treatments may be most effective.

In reviewing viral load and antibody biomarkers, researchers found MIS-C cases with detectable virus had a lower viral load than in primary SARS-CoV-2 infection cases, but similar to MIS-C controls who had alternative diagnoses, but who also had detectable virus. A larger proportion of patients with MIS-C had detectable SARS-CoV-2 antibodies than controls. This is consistent with current thinking that MIS-C occurs a few weeks after a primary COVID-19 infection as part of an overzealous immune response.

Viral sequencing was also performed in the MIS-C cohort and compared to cases of primary COVID-19 infection in the Children’s National geographic population. 88% of the samples analyzed fell into the GH clade consistent with the high frequency of the GH clade circulating earlier in the pandemic in the U.S. and Canada, and first observed in France.

“The fact that there were no notable sequencing differences between our MIS-C and primary COVID cohorts suggests that variations in host genetics and/or immune response are more likely primary determinants of how MIS-C presents itself, rather than virus-specific factors,” says Dr. DeBiasi. “As we’ve seen new variants continue to emerge, it will be important to study their effect on the frequency and severity of MIS-C.”

Researchers are still looking for consensus on the most efficacious treatments for MIS-C. In a recent editorial in the New England Journal of Medicine, Dr. DeBiasi calls for well-characterized large prospective cohort studies at single centers, and systematic and long-term follow-up for cardiac and non-cardiac outcomes in children with MIS-C. Data from these studies will be a crucial determinant of the best set of treatment guidelines for immunotherapies to treat MIS-C.

boy in hospital bed

Long-term, controlled studies needed to chart optimal MIS-C immunotherapy

boy in hospital bed

Roberta L. DeBiasi, M.D., chief of the Division of Pediatric Infectious Diseases at Children’s National Hospital, cautions that two new studies in the New England Journal of Medicine present seemingly conflicting findings about which treatments for MIS-C are optimal.

Multisystem inflammatory disease in children (MIS-C) has affected nearly 4,000 children in the United States in the last year. Two major studies appearing in the June edition of the New England Journal of Medicine seek to better define which immunotherapy treatments or combinations of treatments — intravenous immune globulin (IVIG), glucocorticoids or biologics — do the best job of combating the syndrome’s effects.

But Roberta L. DeBiasi, M.D., chief of the Division of Pediatric Infectious Diseases at Children’s National Hospital, cautions that though these two studies present seemingly conflicting findings about which treatments are optimal, neither study can provide a complete picture of efficacy, in part due to their retrospective and observational study design and population made up of patients from many different centers. True consensus will likely be found, she writes in an editorial that accompanies the studies in the journal, through single-center prospective cohort studies with standardized treatment approaches and long-term follow-up on outcomes.

“While there is a diagnostic criterion and an agreed upon need to induce a rapid therapy for MIS-C, the scientific community has not been able to agree on specific and optimal forms of immunomodulatory therapy,” she writes.

Despite efforts by the study authors to use statistical methods and modeling to control for variations in treatment applications from center to center, the study data is limited by the fact that the therapies have already been administered, in various combinations, based on conditions at each center where a  child was treated and not on a common set of treatment criteria.

Another challenge for generalizing from the findings of these studies is a mismatch in time. The data collected from the two published studies have two different time frames: before and after variants emerged or at various points during different waves of COVID-19 circulation in the U.S.

“Depending on the strain of initial infection and/or subsequent exposure, the dysregulated hyperimmune response of MIS-C could change,” Dr. DeBiasi says. And along with it, how patients respond to a particular treatment or combination of treatments.

Also, she notes it is too soon for any consortia to assess the impact of these therapies on longer-term outcomes, “specifically, comparative efficacy for progression or resolution of coronary abnormalities and prolonged or permanent cardiac dysfunction or scarring.”

Dr. DeBiasi concludes her editorial with a call for well-characterized large prospective cohort studies at single centers, and systematic and long-term follow-up for cardiac and non-cardiac outcomes in children with MIS-C. Data from these studies will be a crucial determinant of the best set of treatment guidelines for immunotherapies to treat MIS-C. Without findings from these types of studies, the selection of the most efficacious treatments is still unknown.

Read the full editorial in the New England Journal of Medicine: Immunotherapy for MIS-C: IVIG, Glucocorticoids, and Biologics

US News badges

For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fifth year in a row.

For the eleventh straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgerygastroenterology and gastro-intestinal surgery, and urology.