Infectious Disease

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.

coronavirus

Children have more COVID-19 antibodies than previously thought, study finds

coronavirus

Seroprevalence of antibodies to SARS-CoV-2 in healthy children and children with chronic diseases is higher than researchers previously believed, according to a new study published in The Pediatric Infectious Diseases Journal. The study, which included 385 children in the Washington metropolitan area, found a 9.46% SARS-CoV-2 seroprevalence among this group. Researchers from Children’s National Hospital also identified predictive factors such as specific symptoms, race and ethnicity, that are associated with the antibodies’ presence in the blood, also known as seropositivity.

The 9.46% seroprevalence in healthy children and children with chronic diseases is higher than previously reported. However, this rate remains below the theoretical herd immunity threshold, estimated between 50% and 67% for the general population in the absence of any interventions — like vaccination — and assuming possible lasting immunity.

“We believe our estimate is a close approximation of seroprevalence for the diverse pediatric population in our region,” said the study authors, including Burak Bahar, M.D., lead author and director of Laboratory Informatics at Children’s National.

Since most symptomatic individuals are adults and they have been the main focus for seroprevalence studies, there is still a lack of information about SARS-CoV-2 seroprevalence for pediatric patients and healthy kids. With this study, researchers wanted to shed light on the knowledge gap in COVID-19 pediatric research.

“Parents are key allies who can help scientists better understand the virus’ behavior in children,” said Dr. Bahar.

Until now, it was also unknown if children with chronic diseases had less evidence of antibodies due to underlying conditions, particularly illnesses that cause weakened immune systems. The study showed no notable difference in the association with seropositivity among chronic illness groups, including immunocompromised children.

“Our findings offer important information as all children, with chronic illness or not, could be considered for ‘back to school’ transitions, because they have the same levels of protection. This means they all can have access to social, emotional and behavioral development,” said the authors.

The researchers explored co-existing conditions, symptomatology and demographics as predictors of antibody presence. The analysis showed that children with chronic conditions like asthma, diabetes and cancer were not predictors. This means that these sick kids, when introduced to the virus, make antibodies at the same levels as kids without these diseases.

While most participants were asymptomatic, in those who tested positive for anti-SARS-CoV-2 antibodies, fever, headache and cough were the most common symptoms.

Among the demographics, Hispanic children had a higher seropositive rate than white children. However, median household income based on reported zip code and state of residency were not found to be associated with having antibodies or not.

To determine the impact of continued infections in the community, future studies are needed to identify possible changes in the seroprevalence over a more extended period and to assess seropositivity with vaccination implementation, as that may influence the current rate.

The study is a snapshot in time from July to October 2020. The sample size of 385 patients included both healthy children and those with chronic diseases (69.7%) ranging from 2 months to 22 years old. From the sample pool, 38 individuals were found to have antibodies against SARS-CoV-2. To assess demographic characteristics, symptoms and co-existing conditions associated with seropositivity the researchers used a survey.

A related SARS-CoV-2 antibody production study published on Sept. 3, 2020 in the Journal of Pediatrics, also led by Bahar et al., found that antibodies are detected 18 days after a positive COVID-19 test in children. The authors further noted that the virus and antibodies can co-exist in young patients, so even if seropositivity is detected, they may still transmit the virus.

HIV Viruses

New pre-clinical model could hold the key to better HIV treatments

HIV Viruses

A team led by researchers at Weill Cornell Medicine and Children’s National Hospital has developed a unique pre-clinical model that enables the study of long-term HIV infection, and the testing of new therapies aimed at curing the disease.

A team led by researchers at Weill Cornell Medicine and Children’s National Hospital has developed a unique pre-clinical model that enables the study of long-term HIV infection, and the testing of new therapies aimed at curing the disease.

Ordinary subjects in this model cannot be infected with HIV, so previous HIV pre-clinical models have used subjects that carry human stem cells or CD4 T cells, a type of immune cell that can be infected with HIV. But these models tend to have limited utility because the human cells soon perceive the tissues of their hosts as “foreign,” and attack—making the subject gravely ill.

By contrast, the new pre-clinical model, described in a paper in the Journal of Experimental Medicine on 14 May, avoids this problem by using a subset of human CD4 cells that mostly excludes the cells that would attack the subject’s tissue. The researchers showed that the subject can usefully model the dynamics of long-term HIV infection, including the virus’s response to experimental therapies.

“We expect this to be a valuable and widely used tool for studying the basic science of HIV infection, and for speeding the development of better therapies,” said co-first author Dr. Chase McCann. During the study, Dr. McCann was a Weill Cornell Graduate School student in the laboratory of senior author Dr. Brad Jones, associate professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine. Dr. McCann, who was supported at Weill Cornell by a Clinical and Translational Science Center (CTSC) TL1 training award, is now the Cell Therapy Lab Lead in the Center for Cancer and Immunology Research at Children’s National Hospital in Washington, D.C. The other co-first authors of the study are Dr. Christiaan van Dorp of Los Alamos National Laboratory and Dr. Ali Danesh, a senior research associate in medicine at Weill Cornell Medicine.

The invention of the new pre-clinical model is part of a wider effort to develop and test cell therapies against HIV infection. Cell therapies, such as those using the patient’s own engineered T cells, are increasingly common in cancer treatment and have achieved some remarkable results. Many researchers hope that a similar strategy can work against HIV and can potentially be curative. But the lack of good pre-clinical models has hampered the development of such therapies.

Drs. Jones and McCann and their colleagues showed in the study that the cell-attacks-host problem found in prior pre-clinical models is chiefly due to so-called “naïve” CD4 cells. These are CD4 cells that have not yet been exposed to targets, and apparently include a population of cells that can attack various proteins. When the researchers excluded naïve CD4 cells and instead used only “memory” CD4 cells, which circulate in the blood as sentinels against infection following exposure to a specific pathogen, the cells survived indefinitely in the subject without causing major damage to their hosts.

The researchers observed that the human CD4 cells also could be infected and killed by HIV, or protected by standard anti-HIV drugs, essentially in the same way that they are in humans. Thus, they showed that the subject, which they termed “participant-derived xenograft” or PDX, served as a workable model for long-term HIV infection. This term is akin to the “patient-derived xenograft” PDX models used to study cancer therapies, while recognizing the contributions of people with HIV as active participants in research.

Lastly, the researchers used the new model to study a prospective new T-cell based therapy, very similar to one that is now being tested against cancers. They put memory CD4 T cells from a human donor into the subject to permit HIV infection, and then, after infection was established, treated the subject with another infusion of human T cells, these being CD8-type T cells, also called “killer T cells.”

The killer T cells were from the same human donor and could recognize a vulnerable structure on HIV — so that they attacked the virus wherever they found it within the subject. To boost the killer T cells’ effectiveness, the researchers supercharged them with a T cell-stimulating protein called IL-15.

The treatment powerfully suppressed HIV in the subject. And although, as often seen in human cases, the virus ultimately evolved to escape recognition by the killer T cells, the ease of use of the pre-clinical model allowed the researchers to monitor and study these long-term infection and viral escape dynamics in detail.

“I think that the major impact of this model will be its acceleration of the development of T cell-based therapies that can overcome this problem of viral escape,” Dr. Jones said.

He and his laboratory are continuing to study such therapies using the new pre-clinical model, with engineered T cells from Dr. McCann’s laboratory and others.

A version of this story appeared on the Weill Cornell Medicine newsroom.

antibodies attacking t-cell

Immunocompromised pediatric patients show T-cell activity against SARS-CoV-2

antibodies attacking t-cell

The study, published in the Journal of Clinical Immunology, suggests that patients with antibody deficiency disorders, including inborn errors of immunity (IEI) and common variable immunodeficiency (CVID), can mount an immune response to SARS-CoV-2 and proposes that vaccination may still be helpful for this population.

According to data from a cohort of adult and pediatric patients with antibody deficiencies, patients that often fail to make protective immune responses to infections and vaccinations showed robust T-cell activity and humoral immunity against SARS-CoV-2 structural proteins. The new study, led by researchers at Children’s National Hospital, is the first to demonstrate a robust T-cell response against SARS-CoV-2 in immunocompromised patients.

“If T-cell responses to SARS-CoV-2 are indeed protective, then it could suggest that adoptive T-cell immunotherapy might benefit more profoundly immunocompromised patients,” said Michael Keller, M.D., director of the Translational Research Laboratory in the Program for Cell Enhancement and Technologies for Immunotherapy (CETI) at Children’s National. “Through our developing phase I T-cell immunotherapy protocol, we intend to investigate if coronavirus-specific T-cells may be protective following bone marrow transplantation, as well as in other immunodeficient populations.”

The study, published in the Journal of Clinical Immunology, showed that patients with antibody deficiency disorders, including inborn errors of immunity (IEI) and common variable immunodeficiency (CVID), can mount an immune response to SARS-CoV-2. The findings propose that vaccination may still be helpful for this population.

“This data suggests that many patients with antibody deficiency should be capable of responding to COVID-19 vaccines, and current studies at the National Institutes of Health and elsewhere are addressing whether those responses are likely to be protective and lasting,” said Dr. Keller.

The T-cell responses in all the COVID-19 patients were similar in magnitude to healthy adult and pediatric convalescent participants.

Kinoshita et al. call for additional studies to further define the quality of the antibody response and the longevity of immune responses against SARS-CoV-2 in immunocompromised patients compared with healthy donors. Currently, there is also very little data on adaptive immune responses to SARS-CoV-2 in these vulnerable populations.

The study sheds light on the antibody and T-cell responses to SARS-CoV-2 protein spikes based on a sample size of six patients, including a family group of three children and their mother. All have antibody deficiencies and developed mild COVID-19 symptoms, minus one child who remained asymptomatic. Control participants were the father of the same family, who tested positive for COVID-19, and another incidental adult (not next of kin) experienced mild COVID-19 symptoms. The researchers took blood samples to test the T-cell response in cell cultures and provided comprehensive statistical analysis of the adaptive immune responses.

“This was a small group of patients, but given the high proportion of responses, it does suggest that many of our antibody deficient patients are likely to mount immune responses to SARS-CoV-2,” said Dr. Keller. “Additional studies are needed to know whether other patients with primary immunodeficiency develop immunity following COVID-19 infection and will likely be answered by a large international collaboration organized by our collaborators at the Garvan Institute in Sydney.”

Francis Collins

Francis S. Collins, M.D., Ph.D. from NIH: The future of genomic medicine and research funding opportunities

Kurt Newman and Francis Collins

Genomic medicine, diversity, equity and inclusion (DEI), a world post-COVID-19 and pediatric research funding were among the topics discussed during the “Special Fireside Chat” keynote lecture at the 2021 Children’s National Hospital Research, Education and Innovation Week.

Francis S. Collins, M.D., Ph.D., director at the National Institutes of Health (NIH), is well known for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.

The President and CEO of Children’s National, Kurt Newman, M.D., joined Dr. Collins during the “Special Fireside Chat” keynote lecture. Dr. Newman posed several health care-related questions to Dr. Collins over the course of 30 minutes. Dr. Collins’s responses shed light on what it takes to advance various research fields focused on improving child health and develop frameworks that advocate for DEI in order to foster a more just society.

Q: You have been involved with genomic medicine since its inception. You discovered the gene causing cystic fibrosis and led the Human Genome project. What do you see as the future of genomic medicine, especially as it relates to improving child health?

A: Thank you for the question, Kurt. First, I wanted to say congratulations on your 150th anniversary. Children’s National Hospital has been such a critical component for pediatric research and care in the Washington, D.C., area, and at the national and international levels. We at the NIH consider it a great privilege to be your partner in many of the things that we can and are doing together.

Genomic medicine has certainly come a long way. The word genomics was invented in 1980, so we have not been at this for that long. Yet, the success of the Human Genome Project and the access to cost-effective tools for rapid DNA sequencing have made many things possible. It took a lot of effort, time and money to discover the gene that causes cystic fibrosis. Kurt, if you look at what we did, while it was rewarding, it was a challenging problem that occupied the hearts of the scientific community in 1980. Now, a graduate student at Children’s National that has access to DNA samples, a thermal cycler, a DNA sequencer and the internet could do in about a week what it took us a decade and with 50 people.

We have been able to rocket forward as far as identifying the genetic causes of 6,500 diseases, where we know precisely the molecular glitch responsible for those conditions. While most of those are rare diseases, it leads to the opportunity for immediate diagnosis, which used to be a long and troubled journey.

DNA sequencing has increasingly become an essential tool in newborns, especially when trying to sort out puzzling diagnosis for specific syndromes or phenotypes that are not immediately clear. Additionally, DNA sequencing significantly impacted clinical care in cancer because it made it possible to look at the mutations driving the malignancy and its genetic information that can lead to interventions. This approach is going forward in the next few years in ways that we can see now. Although I am a little reluctant to make predictions because I have to be careful about that, it may be possible to obtain complete genome sequences that can be yours for life and place them into the medical record to make predictions about future risks and choices about appropriate drugs. This path costs less than any imaging tests.

Q: The racial justice movement that was brought back to the forefront this past year has, once again, reaffirmed that this country has so much more work to do in order to end systemic racism. You have been at the forefront of promoting diversity, equity and inclusion in research and at the NIH. What do you and the NIH plan to do further DEI efforts in research and in general so that we can be a more just and equitable society?

A: I appreciate you raising this, Kurt. Diversity, equity and inclusion (DEI) is an issue where everyone should be spending a lot of time, energy and passion. You are right. 2020 will be remembered for COVID-19. I also think it will be remembered for the things that occurred around the killing of George Floyd, and the recognition of the very foundation that is still infected by this terribly difficult circumstance of structural racism. I convened a group of about 75 deep thinkers about these issues, many of them are people of color from across the NIH’s different areas of activities. I asked the group to come forward with a bold set of proposals. This effort is how the program UNITE came together to work hard on this, which is now making recommendations that I intend to follow. We are determined to close that gap and pursue additional programs that will allow us to be more successful in recruiting and retaining minority groups, for example. We need to do something with our health disparity and research portfolio as well to ensure that we are not just looking around the edges of the causes for racial inequities. We are digging deeper into what the structural racism underpinnings are and what we can do about it. I am particularly interested in supporting research projects that test intervention and not just catalog the factors involved. We have been, at times, accused and maybe rightly so of being more academic about this, and, less kindly, we have been accused of admiring the problem of health disparities as opposed to acting on it. We are ready to act.

Q: COVID has affected us all in so many ways. Could you tell us what this past year has been like for you? Also, how is the NIH preparing for a soon-to-be post-COVID pandemic?

A: This is the time to contemplate the lessons learned as everyone knows that the last worst pandemic happened over a century ago. One thing that maybe will vex us going forward, which we already started to invest in a big way, is this whole long COVID syndrome, also referred to post-acute sequelae, to understand precisely the consequences and mechanisms like Multisystem Inflammatory Syndrome in Children (MIS-C). Before moving to the next pandemic, we must think about how we will help understand those who suffer from long COVID syndrome. As far as the broader lessons learn, Kurt, we must expect that there will be other pandemics because humans are interacting more with animals, so zoonosis is likely to emerge. We need to have a clear sense of preparation for the next one. For instance, we are working on this right now, but we need to have a stronger effort to develop small molecules of anti-viral drugs aimed at the major viral classes, so we do not have to start from scratch. We also need clinical trial networks warm all the time, ready to go and to learn how valuable public partnerships can be to get things done in a hurry.

Editor’s Note: The responses in this Q+A have been modified to fit the word count.

Andrea Hahn

Pediatric Research names Andrea Hahn, M.D., M.S., early career investigator

Andrea Hahn

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

For her work on the impact of bacterial functional and metabolic activity on acute episodes of cystic fibrosis, the journal Pediatric Research recognized Andrea Hahn, M.D., M.S., as Pediatric Research’s Early Career Investigator.

Cystic fibrosis is an autosomal recessive genetic disease, affecting more than 70,000 people worldwide. The condition’s morbidity and mortality are recurrent and result in a progressive decline of lung function.

“I am honored to be recognized by Pediatric Research and the Society of Pediatric Research (SPR) at large,” said Dr. Hahn. “SPR is an amazing organization filled with excellent scientists, and to be highlighted by them for my work is truly affirming.”

The exact mechanisms of the bacteria that chronically infect the airway triggering acute cystic fibrosis episodes, also known as pulmonary exacerbations, remain unclear. Dr. Hahn’s research is one of the few to explore this gap and found an association with long-chain fatty acid production in cystic fibrosis inflammation.

“As a physician-scientist, there are many competing priorities between developing and executing good science — including writing manuscripts and grants — and providing excellent patient care both directly and through hospital-wide quality improvement initiatives,” said Dr. Hahn. “It is often easier to have successes and feel both effective and appreciated on the clinical side. This recognition of my scientific contributions to the medical community is motivating me to continue pushing forward despite the setbacks that often come up on the research side.”

The exposure to many programs and institutions gave Dr. Hahn the foundation to create a research program at Children’s National that helps decipher the complexities of antibiotic treatment and how it changes the airway microbiome of people with cystic fibrosis. The program also explores the impacts of antibiotic resistance and beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) — the oldest class of antibiotics used to treat infections.

Dr. Hahn believes that the people and environment at Children’s National Hospital allowed her to grow and thrive as a physician-scientist.

“I was initially funded through an internal K12 mechanism, which was followed up by Foundation support, which was only possible because of the strong mentorship teams I have been able to build here at Children’s National,” said Dr. Hahn. “My division chief has also been very supportive, providing me with both protected time as well as additional resources to build my research lab.”

She is particularly appreciative of Robert Freishtat, M.D., M.P.H, senior investigator at the Center for Genetic Medicine Research, and Mary Callaghan Rose (1943-2016).

“Robert Freishtat has been a great advocate for me, and I am indebted to him for my success thus far in my career,” said Dr. Hahn. “Likewise, I want to specifically recognize Mary Rose. She was a great scientist at Children’s National until her death in 2016. She gave me the initial opportunity and support to begin a career studying cystic fibrosis, and she is missed dearly.”

You can learn more about Dr. Hahn’s research in this Pediatric Research article.

coronavirus

An analysis of articles on pediatric COVID-19 cases

coronavirus

In a recent editorial, Dr. Briony Varda commented on a systematic review and meta-analysis of articles reporting on pediatric cases of COVID-19.

In a recent editorial, Children’s National Hospital Pediatric Urologist Briony Varda, M.D., M.P.H., and Emilie K. Johnson, M.D., M.P.H., from Ann & Robert H. Lurie Children’s Hospital of Chicago, comment on a systematic review and meta-analysis of articles reporting on pediatric cases of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Their take home messages were that although COVID-19 is typically milder in children than in adults, children (particularly infants) do appear to have cardiac damage from COVID-19 which may be a consideration for preoperative evaluation among surgeons. They also note the MIS-C is another emerging concern for children following an infection with COVID-19.

Read the full editorial in the Journal of Pediatric Urology.

girl with cystic fibrosis getting breathing treatment

The role of long-chain fatty acids in cystic fibrosis inflammation

girl with cystic fibrosis getting breathing treatment

A recent study sheds light on the microbiologic triggers for lung inflammation and pulmonary exacerbations in cystic fibrosis.

Cystic fibrosis is an autosomal recessive disease that affects more than 70,000 people worldwide and results in a progressive decline of lung function. Patients with cystic fibrosis experience intermittent episodes of acute worsening of symptoms, commonly referred to as pulmonary exacerbations. While Staphylococcus aureus and Pseudomonas aeruginosa are thought to contribute to both lung inflammation and pulmonary exacerbations, the microbiologic trigger for these events remains unknown. Andrea Hahn, M.D., M.S., and her colleagues at Children’s National Hospital recently shed light on this matter by studying the changes in bacterial metabolic pathways associated with clinical status and intravenous (IV) antibiotic exposure in cystic fibrosis patients.

The researchers found increased levels of long-chain fatty acids (LCFAs) after IV antibiotic treatment in patients with cystic fibrosis. LCFAs have previously been associated with increased lung inflammation in asthma, but this is the first report of LCFAs in the airway of people with cystic fibrosis. This research indicates that bacterial production of LCFAs may be a contributor to inflammation in people with cystic fibrosis and suggests that future studies should evaluate LCFAs as predictors of pulmonary exacerbations.

Additional authors from Children’s National include: Hollis Chaney, M.D., Iman Sami Zakhari, M.D., Anastassios Koumbourlis, M.D., M.P.H. and Robert Freishtat, M.D., M.P.H.

Read the full study in Pediatric Research.

illustration of lungs with coronavirus inside

Pediatric asthma exacerbations during the COVID-19 pandemic

illustration of lungs with coronavirus inside

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years.

In the United States, pediatric asthma exacerbations typically peak in the fall due to seasonal factors such as increased spread of common respiratory viruses, increased exposure to indoor aeroallergens, changing outdoor aeroallergen exposures and colder weather. In early 2020, measures enacted to reduce spread of the coronavirus (COVID-19) — such as social distancing, quarantines and school closures — also reduced pediatric respiratory illnesses and asthma morbidity. Children’s National Hospital immunologist and allergist William J. Sheehan, M.D., and colleagues sought to determine if these measures also affected the 2020 fall seasonal asthma exacerbation peak in Washington, D.C.

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years. Emergency department visits, hospitalizations and intensive care unit admissions for asthma during the 2020 fall season were significantly reduced compared to previous years.

The authors conclude that, “this is likely due to social distancing, quarantines and school closures enacted during the pandemic. This is a small silver lining in a very difficult year. As 2021 brings optimism for gradual improvements of the pandemic, careful monitoring is necessary to recognize and prepare for childhood asthma morbidity to return to pre-pandemic levels.”

Additional study authors include: Shilpa J. Patel, M.D., M.P.H., Rachel H.F. Margolis, Ph.D., Eduardo R. Fox, M.D., Deborah Q. Shelef, M.P.H., Nikita Kachroo, B.S., Dinesh Pillai, M.D. and Stephen J. Teach, M.D., M.P.H.

Read the full study in the Journal of Allergy and Clinical Immunology: In Practice.

Asthma-Related Healthcare Utilization by Month

Asthma-Related Healthcare Utilization by Month (2016-2020). Asthma-related emergency department (ED) visits, hospitalizations and pediatric intensive care unit (PICU) admissions over time by month between 2016 and 2020. The p-values are for comparisons of mean monthly numbers for fall seasons of 2016-2019 to fall season of 2020. Image courtesy of the Journal of Allergy and Clinical Immunology: In Practice.