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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.

Screenshot of Drs. Northam, Newman and Batshaw

4th Annual Children’s National Hospital-NIAID Virtual Symposium

Screenshot of Drs. Northam, Newman and Batshaw

Keynote speaker Virginia Governor and pediatric neurologist, Ralph Northam, joined Dr. Kurt Newman, president and CEO of Children’s National Hospital, and Dr. Mark Batshaw, executive vice president, physician-in-chief and chief academic officer at Children’s National Hospital, during the 4th Annual Children’s National Hospital-NIAID Virtual Symposium.

Children’s National Hospital and the National Institute of Allergy and Infectious Diseases (NIAID) hosted their 4th annual symposium, attracting nationwide researchers, trainees and health care professionals to share updates on the COVID-19-related condition known as Multisystem Inflammatory Syndrome (MIS-C) in Children, allergy and immunology in the pediatric population.

“Children’s National relationship with the NIAID is a strategic and novel alliance that benefits children everywhere,” said Kurt Newman, M.D., President and CEO of Children’s National Hospital. “I’m so proud of our unique partnership and how it has enriched the high-quality research being conducted at Children’s National and enabled us to interact on pressing health issues. With the opening of our new Children’s National Research & Innovation Campus on the grounds of the former Walter Reed Army Medical Center, the sky is the limit to how we can work together with the NIAID to innovate for kids so that we help them grow up stronger.”

The discussions at the symposium centered around various topics, including clinical manifestations of SARS-CoV-2 in children, comparative disease biology manifestation in children and adults, therapies and vaccines in the pediatric setting, intersectionality of allergy, immunology and COVID-19, modulating biologic factors in immune regulation and treatments that invoke tolerance in allergy.

Keynote speaker Virginia Governor and pediatric neurologist, Ralph Northam, spoke about the COVID-19 pandemic and strategies to reintroduce children into schools and sports.

“Schools provide stability and structure. We know that children need to be in school for educational achievements and their mental health, but it has taken time to make school staff and families more comfortable with a greater time of in-person learning,” said Dr. Northam. “Our goal is to have all in-person learning this fall. That is where our children need to be because it is the safest place for children.”

During the keynote session, Dr. Northam also addressed the mental health issues related to the pandemic where pediatricians have seen an increase in depression and suicide rates.

“As we move forward to a back more normal life, we need to keep an eye on these children and make sure that they continue to get the support and treatment that they need,” said Dr. Northam.

Below are the speakers and the focus of their presentations.

  • Post-COVID cardiac manifestations in children: Anita Krishnan, M.D., Children’s National
  • Immunomodulation and Cytokine Profiling in MIS-C: Hemalatha Srinivasalu, M.D., Children’s National
  • The MUSIC study: Long-TerM OUtcomes After the Multisystem Inflammatory Syndrome in Children: Jane Newburger, M.D., Boston Children’s Hospital
  • MIS-C in Typical Cases and Down Syndrome: Dusan Bogunovic, M.D., Mount Sinai
  • Age-Related Virus-Specific T-Cell Responses to SARS-CoV-2: Susan Conway, M.D., Children’s National
  • Systems Immunology of COVID-19: Integrating Patient and Single Cell Variations: John Tsang, Ph.D., NIAID
  • Therapeutics for Children with COVID-19: Trying to be Data Driven in the Absence of Pediatric Trials: Andy Pavia, M.D., University of Utah
  • SARS-CoV-2 Vaccine Clinical Research: Alicia Widge, M.D., NIAID
  • Implementation and Public Health Aspects: Cara Biddle, M.D., M.P.H., Children’s National
  • COVID-19 and Pediatric Asthma: William Sheehan, M.D., Children’s National
  • The COVID-19 Pandemic and Immunodeficiency: The Burden and Emerging Evidence: Jessica Durkee-Shock, M.D., NIAID
  • SARS-CoV-2 Infection in Children with Cancer: The MSK Experience: Andy Kung, M.D., Memorial Sloan Kettering
  • Adaptive and Maladaptive Immunity to the Microbiota: Implication for Inflammatory Disorders: Yasmine Belkaid, M.D., NIAID
  • Deep Immune Profiling of Peanut Reactive CD4+ T-Cells Reveals Distinct Immunotypes Link to Clinical Outcome: Erik Wambre, M.D., Benaroya Research Institute
  • B Cells and Food Allergy: Not Just for Making IgE: Adora Lin, M.D., Ph.D., Children’s National
  • Emerging Biologic Therapies for Food Allergy: Hemant Sharma, M.D., Children’s National
  • The Promise and Limits of Allergen Immunotherapy: Carla Davis, M.D., Texas Children’s
  • Maternal Fetal Interactions in Food Tolerance: Michiko Oyoshi, M.D., Harvard Medical School

The Clinical and Translational Science Institute at Children’s National (CTSI-CN) and the NIAID organized the 4th annual symposium and wished to showcase some of the critical research being done on this worldwide infectious disease, particularly amongst the pediatric population and those affected with allergic and immunologic disease. By sharing this work, they hope it will help continue to drive the advancement of pediatric research in relation to this disease.

The research partnership between Children’s National and the National Institute of Allergy and Infectious Diseases (NIAID) is devoted to protecting and advancing the health of children with allergic, immunologic, autoinflammatory and infectious diseases through collaborative research and education. The partnership co-hosts an annual symposium to disseminate new information about science related to the partnership.

To view all the presentations from the symposium, click here.

For questions about the symposium or projects there, contact: CN-NIAIDPartnership@childrensnational.org.

NIAID Symposium banner

girl with asthma inhaler

Children’s National becomes part of CAUSE Network

girl with asthma inhaler

Seven clinical sites in six different cities will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

The National Institute of Allergy and Infectious Diseases (NIAID) allocated $10 million in funding to establish the Childhood Asthma in the Urban Setting (CAUSE) network. The NIAID plans to increase this number by $70 million over seven years to support the network. Children’s National Hospital will be part of the new research network, which is a 7-year consortium comprising of seven clinical sites in six different cities that will join forces to perform mechanistic and translational studies examining the basic immunology of pediatric asthma among urban, under-resourced and largely minority children and adolescents.

Children’s National is the home of Improving Pediatric Asthma Care in the District of Columbia (IMPACT DC). The program focuses on research, care and advocacy to decrease asthma morbidity experienced by at-risk youth in the region while serving as a model program for the nation. NIAID gave an initial $3 million to IMPACT DC to conduct its own pilot study of anti-IgE therapy to prevent asthma exacerbations. Additional support for this and other studies will come from subcontracts from the CAUSE Coordinating Center at the University of Wisconsin in Madison.

“This new award allows IMPACT DC to remain part of one of the nation’s most prestigious pediatric asthma research consortia,” said Stephen Teach, M.D, M.P.H., chair for the Department of Pediatrics at George Washington University School of Medicine and Health Sciences. “It will allow us to both pursue an independent research agenda while collaborating with similar academic centers nationwide.”

Pediatric asthma is the most common chronic disease in children, and it is estimated that about 6.1 million children under 18 years suffer from this condition. It disproportionately affects urban, minority and under-resourced children and adolescents.

“It is essential to develop an understanding of the basic immunology of the disease and therapeutic options to ameliorating these disparities,” said Dr. Teach.

CAUSE researchers will explore the mechanisms of immune tolerance to allergens, the role of early environmental exposures in the pathogenesis of asthma, the pathogenesis and mechanisms of non-atopic asthma, the role of the respiratory epithelium in asthma and more.

The CAUSE network comprises of seven clinical research centers, including Children’s National led by principal investigator, Dr. Teach, and the following research centers:

  • Boston Children’s Hospital. Principal investigators: Wanda Phipatanakul, M.D., and Talal Chatila, M.D.
  • Cincinnati Children’s Hospital Medical Center. Principal investigator: Gurjit Khurana Hershey, M.D., Ph.D.
  • Columbia University Health Sciences, New York. Principal investigator: Meyer Kattan, M.D.
  • Icahn School of Medicine at Mount Sinai, New York. Principal investigators: Paula Busse, M.D., Supinda Bunyavanich, M.D., and Juan Wisnivesky, M.D.
  • Lurie Children’s Hospital of Chicago. Principal investigators: Rajesh Kumar, M.D., and Jacqueline Pongracic, M.D.
  • University of Colorado Denver. Principal investigator: Andrew Liu, M.D.
coronavirus

COVID-19 Pandemic: 3rd Annual CN – NIAID Virtual Symposium

The CN-NIAID Virtual Symposium highlighted work being done to fight the COVID-19 pandemic globally.

Vittorio Gallo and Mark Batshaw

Children’s National Research Institute releases annual report

Vittorio Gallo and Marc Batshaw

Children’s National Research Institute directors Vittorio Gallo, Ph.D., and Mark Batshaw, M.D.

The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.

“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”

Highlights from the Children’s National Research Institute annual report

  • In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
  • In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
  • A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
  • The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
  • Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
  • An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
  • In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
  • Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.

Understanding and treating the novel coronavirus (COVID-19)

In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:

  • Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
  • Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
  • Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.

You can view the entire Children’s National Research Institute academic annual report online.

t-cells

Tailored T-cell therapies neutralize viruses that threaten kids with PID

t-cells

Tailored T-cells specially designed to combat a half dozen viruses are safe and may be effective in preventing and treating multiple viral infections, according to research led by Children’s National Hospital faculty.

Catherine Bollard, M.B.Ch.B., M.D., director of the Center for Cancer and Immunology Research at Children’s National and the study’s senior author, presented the teams’ findings Nov. 8, 2019, during a second-annual symposium jointly held by Children’s National and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Children’s National and NIAID formed a research partnership in 2017 to develop and conduct collaborative clinical research studies focused on young children with allergic, immunologic, infectious and inflammatory diseases. Each year, they co-host a symposium to exchange their latest research findings.

According to the NIH, more than 200 forms of primary immune deficiency diseases impact about 500,000 people in the U.S. These rare, genetic diseases so impair the person’s immune system that they experience repeated and sometimes rare infections that can be life threatening. After a hematopoietic stem cell transplantation, brand new stem cells can rebuild the person’s missing or impaired immune system. However, during the window in which the immune system rebuilds, patients can be vulnerable to a host of viral infections.

Because viral infections can be controlled by T-cells, the body’s infection-fighting white blood cells, the Children’s National first-in-humans Phase 1 dose escalation trial aimed to determine the safety of T-cells with antiviral activity against a half dozen opportunistic viruses: adenovirus, BK virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human Herpesvirus 6 and human parainfluenza-3 (HPIV3).

Eight patients received the hexa-valent, virus-specific T-cells after their stem cell transplants:

  • Three patients were treated for active CMV, and the T-cells resolved their viremia.
  • Two patients treated for active BK virus had complete symptom resolution, while one had hemorrhagic cystitis resolved but had fluctuating viral loads in their blood and urine.
  • Of two patients treated prophylactically, one developed EBV viremia that was treated with rituximab.

Two additional patients received the T-cell treatments under expanded access for emergency treatment, one for disseminated adenoviremia and the other for HPIV3 pneumonia. While these critically ill patients had partial clinical improvement, they were being treated with steroids which may have dampened their antiviral responses.

“These preliminary results show that hexaviral-specific, virus-specific T-cells are safe and may be effective in preventing and treating multiple viral infections,” says Michael Keller, M.D., a pediatric immunologist at Children’s National and the lead study author. “Of note, enzyme-linked immune absorbent spot assays showed evidence of antiviral T-cell activity by three months post infusion in three of four patients who could be evaluated and expansion was detectable in two patients.”

In addition to Drs. Bollard and Keller, additional study authors include Katherine Harris M.D.; Patrick J. Hanley Ph.D., assistant research professor in the Center for Cancer and Immunology; Allistair Abraham, M.D., a blood and marrow transplantation specialist; Blachy J. Dávila Saldaña, M.D., Division of Blood and Marrow Transplantation; Nan Zhang Ph.D.; Gelina Sani BS; Haili Lang MS; Richard Childs M.D.; and Richard Jones M.D.

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Children’s National-NIAID 2019 symposium presentations

“Welcome and introduction”
H. Clifford Lane, M.D., director of NIAID’s Division of Clinical Research

“Lessons and benefits from collaboration between the NIH and a free-standing children’s hospital”
Marshall L. Summar, M.D., director, Rare Disease Institute, Children’s National

“The hereditary disorders of PropionylCoA and Cobalamin Metabolism – past, present and future”
Charles P. Venditti, M.D., Ph.D., National Human Genome Research Institute Collaboration

“The road(s) to genetic precision therapeutics in pediatric neuromuscular disease: opportunities and challenges”
Carsten G. Bönnemann, M.D., National Institute of Neurological Disorders and Stroke

“Genomic diagnostics in immunologic diseases”
Helen Su, M.D., Ph.D., National Institute of Allergy and Infectious Diseases

“Update on outcomes of gene therapy clinical trials for X-SCID and X-CGD and plans for future trials”
Harry Malech, M.D., National Institute of Allergy and Infectious Diseases

“Virus-specific T-cell therapies: broadening applicability for PID patients”
Catherine Bollard, M.D., Children’s National 

“Using genetic testing to guide therapeutic decisions in Primary Immune Deficiency Disease”
Vanessa Bundy, M.D., Ph.D., Children’s National 

Panel discussion moderated by Lisa M. Guay-Woodford, M.D.
Drs. Su, Malech, Bollard and Bundy
Morgan Similuk, S.C.M., NIAID
Maren Chamorro, Parent Advocate

“Underlying mechanisms of pediatric food allergy: focus on B cells
Adora Lin, M.D., Ph.D., Children’s National 

“Pediatric Lyme outcomes study – interim update”
Roberta L. DeBiasi, M.D., MS, Children’s National 

“Molecular drivers and opportunities in neuroimmune conditions of pediatric onset”
Elizabeth Wells, M.D., Children’s National 

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