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coronavirus molecules with DNA

Novel SARS-CoV-2 spike variant found in a newborn in Washington, D.C.

coronavirus molecules with DNA

Researchers at Children’s National Hospital found a new SARS-CoV-2 spike variant in a neonatal patient, according to a study that genetically sequenced the virus in 27 pediatric patients. The newborn presented with a viral load of 50,000 times more particles than the average patient, which led to identifying the N679S spike protein variant — the earliest known sample of this coronavirus lineage in the U.S. mid-Atlantic region.

While the paper is posted to the preprint server medRxiv and has not been peer-reviewed, it represents an early step towards establishing better surveillance of the COVID-19 pandemic. The new variant helps understand the process of viral adaptation, potentially informing treatment development and vaccine design for any viral variants in the future.

All genomes change and evolve. Additional viral variants are expected to emerge as more patients are infected. The data analysis recognized eight other cases in Washington, D.C., with the N679S variant, pointing toward a European origin due to the genetic similarity between of SARS-CoV-2 strains in the U.S. and United Kingdom.

“We need to sequence more cases to identify variants and stay ahead of the virus,” said Drew Michael, Ph.D., molecular geneticist at Children’s National and senior author of the study. “The United States sequences a tiny fraction of all cases, and because we are not sequencing enough, we are not aware of the variants in SARS-CoV-2 that may be spreading in our community.”

“Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak,” was published on the preprint server medRxiv. Additional authors include Jonathan LoTempio, Erik Billings, Kyah Draper, Christal Ralph, Mahdi Moshgriz, Nhat Duong, Jennifer Dien Bard, Xiaowu Gai, David Wessel, M.D., Roberta L. DeBiasi, M.D., M.S., Joseph M. Campos, Ph.D., Eric Vilain, M.D., Ph.D. and Meghan Delaney, D.O., M.P.H.

You can read the full preprint on medRxiv.

boy checking his blood glucose

There’s still more to learn about COVID-19 and diabetes

boy checking his blood glucose

Researchers have learned a lot about COVID-19 over the past year and are continuing to learn and study more about this infection caused by the SARS-CoV-2 virus. There have been many questions about whether COVID-19 affects people with diabetes differently than those without and why this might occur.

Diabetes experts, like Brynn Marks, M.D., M.S.H.P.Ed., endocrinologist at Children’s National Hospital, have been studying the relationship between COVID-19 and diabetes, especially in the pediatric population. Dr. Marks tells us more about what we know so far and further research that needs to be done when it comes to COVID-19 and diabetes.

1.      What do we know about COVID-19 and its effect on people with known diabetes?

The Centers for Disease Control and Prevention (CDC) currently lists type 2 diabetes (T2D) as a high risk condition for severe illness related to COVID-19 infection, while stating that adults with type 1 diabetes (T1D) might be at increased risk. A recent study from Vanderbilt University found that people with T1D and T2D were at approximately equal risk for complications of COVID-19 infection. As compared to adults without diabetes, adults with T1D and T2D were 3-4 times more likely to be hospitalized and to have greater illness severity. Given these comparable risks, both the American Diabetes Association and the Juvenile Diabetes Research Foundation are lobbying for adults with T1D to be given the same level or priority for COVID-19 vaccines as adults with T2D.

However, as pediatricians, we all know to be wary of extrapolating adult data to pediatrics. Children are less likely to be infected with COVID-19 and if they are, the clinical course is typically mild. To date, there have not been any studies of the impact of COVID-19 on youth with known T2D. Our clinical experience at Children’s National Hospital and reports from international multicenter studies indicate that youth with T1D are not at increased risk for hospitalization from COVID-19 infection. However, paralleling ongoing disparities in T1D care, African Americans with known T1D and COVID-19 infection were more likely to be develop diabetic ketoacidosis (DKA) than their White counterparts.

With the increased use of diabetes technologies, including continuous glucose monitors, insulin pumps and automated insulin delivery systems, diabetes care lends itself well to telemedicine. Studies from Italy during the period of lockdown showed better glycemic control among youth with T1D. Further studies are needed to better understand the implications of telehealth on diabetes care, particularly among those in rural areas with limited access to care.

Brynn Marks

Diabetes experts, like Brynn Marks, M.D., M.S.H.P.Ed., endocrinologist at Children’s National Hospital, have been studying the relationship between COVID-19 and diabetes, especially in the pediatric population.

2.      What do we know about the impact of the COVID-19 pandemic on children with newly diagnosed diabetes?

Nationwide studies from Italy and Germany over the first few months of the pandemic found no increase in the incidence of pediatric T1D during the COVID-19 pandemic as compared to the year before; in fact, the Italian study found that fewer children were diagnosed with T1D during the pandemic. However, many centers are seeing higher rates of DKA and more severe DKA at diagnosis during the pandemic, possibly due to decreased primary care visits and/or fears of contracting COVID-19 while seeking care.

To date, no studies have been published exploring the incidence of T2D in youth. A group from Children’s National, including myself, Myrto Flokas, M.D., Abby Meyers, M.D., and Elizabeth Estrada, M.D., from the Division of Endocrinology and Randi Streisand, Ph.D., C.D.C.E.S. and Maureen Monaghan, Ph.D., C.D.C.E.S., from the Department of Psychology and Behavioral Health, are gathering data to compare the incidence of T1D and T2D during the pandemic as compared to the year before.

3.      Can COVID-19 cause diabetes to develop?

This has been area of great interest, but the jury is still out. The SARS-CoV-2 virus, which causes COVID-19 infection, binds the angiotensin-converting enzyme 2 (ACE2) receptor which is located in many tissues throughout the body, including the pancreas. SARS-CoV-2 has been shown to infect pancreatic tissue leading to impaired glucose stimulated insulin secretion. Although the SARS-CoV-2 virus could plausibly cause diabetes, assessment has been complicated by many confounders that could be contributing to hyperglycemia in addition to or rather than the virus itself. Stress-induced hyperglycemia from acute illness, the use of high dose steroids to treat COVID-19 infection, and the disproportionate rates of infection among those already at high risk for T2D, as well as weight gain due to changes in day-to-day life as a result of social distancing precautions are all likely contributing factors.

FCC Chairwoman Jessica Rosenworcel visited Children’s National Hospital

Acting FCC chairwoman Rosenworcel highlights telehealth for pediatrics

FCC Chairwoman Jessica Rosenworcel visited Children’s National Hospital

Acting FCC Chairwoman Jessica Rosenworcel visited Children’s National Hospital yesterday to highlight the importance of connectivity in healthcare and learn more about how the hospital is using telehealth to serve families during the pandemic. Children’s National Hospital in Washington, D.C., has provided pediatric care for 150 years and is among the nation’s top 10 children’s hospitals. Last year, Children’s National, an academic pediatric health system, saw more than 219,000 children from the capital region and from across the country and around the world.

“So much more can be done to connect children and their families — in both urban and rural parts of the country — to the care they need not only to survive, but to thrive,” said Rosenworcel. “Telehealth can help bridge that gap by bringing specialty care available only in hospital centers to smaller clinics and even the home where problems can be addressed quickly, before they prove life threatening. I was encouraged by the creative work that Children’s National Hospital is doing to address the unique health needs of children from all backgrounds especially during these challenging times.”

Acting Chairwoman Rosenworcel was joined by her colleague FCC Commissioner Nathan Simington for a tour of the hospital, where they met with Shireen Atabaki, M.D., M.P.H., associate medical director of Telehealth, Emergency Medicine physician and program director for the COVID-19 Telehealth Program at Children’s National Hospital. The visit also included a demo of a telehealth robot by Ricardo Munoz, M.D., Cardiac Critical Care Medicine chief, and Alejandro Jose Lopez-Magallon, M.D., medical director of Telemedicine, both at Children’s National.

“The pandemic catapulted telehealth as a tool for the future of health care delivery,” said Dr. Atabaki. “With the support of the FCC, Children’s National is excited to introduce a robot and other state-of-the-art digital health technology to support provider-to-patient pediatric care and expert consultations in our hospital’s emergency departments and across our region. These innovations in telemedicine will facilitate access to specialized expertise and care of COVID-19 patients.”

In May 2020, Children’s National Hospital was approved for funding as part of the FCC’s COVID-19 Telehealth Program and established a regional pediatric telehealth consortium. This will enable the hospital to expand its telehealth platform to support 15 health care sites in the region serving children and young adults, providing care to children with COVID-19, as well as those who are medically vulnerable.

Acting Chairwoman Rosenworcel is committed to closing the digital divide and sees access to telehealth care services — especially for underserved and marginalized communities — as a top priority. To learn more about telehealth efforts at the FCC, including the COVID-19 Telehealth Program and the Connected Care Pilot Program, visit: https://www.fcc.gov/connecting-americans-health-care.

Coronavirus and lungs with world map in the background

Top AI models unveiled in COVID-19 challenge to improve lung diagnostics

Coronavirus and lungs with world map in the background

The top 10 results have been unveiled in the first-of-its-kind COVID-19 Lung CT Lesion Segmentation Grand Challenge, a groundbreaking research competition focused on developing artificial intelligence (AI) models to help in the visualization and measurement of COVID specific lesions in the lungs of infected patients, potentially facilitating more timely and patient-specific medical interventions.

Attracting more than 1,000 global participants, the competition was presented by the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital in collaboration with leading AI technology company NVIDIA and the National Institutes of Health (NIH). The competition’s AI models utilized a multi-institutional, multi-national data set provided by public datasets from The Cancer Imaging Archive (National Cancer Institute), NIH and the University of Arkansas, that originated from patients of different ages, genders and with variable disease severity. NVIDIA provided GPUs to the top five winners as prizes, as well as supported the selection and judging process.

“Improving COVID-19 treatment starts with a clearer understanding of the patient’s disease state. However, a prior lack of global data collaboration limited clinicians in their ability to quickly and effectively understand disease severity across both adult and pediatric patients,” says Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, who led the Grand Challenge initiative. “By harnessing the power of AI through quantitative imaging and machine learning, these discoveries are helping clinicians better understand COVID-19 disease severity and potentially stratify and triage into appropriate treatment protocols at different stages of the disease.”

The top 10 AI algorithms were identified from a highly competitive field of participants who tested the data in November and December 2020. The results were unveiled on Jan. 11, 2021, in a virtual symposium, hosted by Children’s National, that featured presentations from top teams, event organizers and clinicians.

Developers of the 10 top AI models from the COVID-19 Lung CT Lesion Segmentation Grand Challenge are:

  1. Shishuai Hu, et al. Northwestern Polytechnical University, China. “Semi-supervised Method for COVID-19 Lung CT Lesion Segmentation”
  2. Fabian Isensee, et al. German Cancer Research Center, Germany. “nnU-Net for Covid Segmentation”
  3. Claire Tang, Lynbrook High School, USA. “Automated Ensemble Modeling for COVID-19 CT Lesion Segmentation”
  4. Qinji Yu, et al. Shanghai JiaoTong University, China. “COVID-19-20 Lesion Segmentation Based on nnUNet”
  5. Andreas Husch, et al. University of Luxembourg, Luxembourg. “Leveraging State-of-the-Art Architectures by Enriching Training Information – a case study”
  6. Tong Zheng, et al. Nagoya University, Japan. “Fully-automated COVID-19-20 Segmentation”
  7. Vitali Liauchuk. United Institute of Informatics Problems (UIIP), Belarus. “Semi-3D CNN with ImageNet Pretrain for Segmentation of COVID Lesions on CT”
  8. Ziqi Zhou, et al. Shenzhen University, China. “Automated Chest CT Image Segmentation of COVID-19 with 3D Unet-based Framework”
  9. Jan Hendrik Moltz, et al. Fraunhofer Institute for Digital Medicine MEVIS, Germany. “Segmentation of COVID-19 Lung Lesions in CT Using nnU-Net”
  10. Bruno Oliveira, et al. 2Ai – Polytechnic Institute of Cávado and Ave, Portugal. “Automatic COVID-19 Detection and Segmentation from Lung Computed Tomography (CT) Images Using 3D Cascade U-net”

Linguraru added that, in addition to an award for the top five AI models, these winning algorithms are now available to partner with clinical institutions across the globe to further evaluate how these quantitative imaging and machine learning methods may potentially impact global public health.

“Quality annotations are a limiting factor in the development of useful AI models,” said Mona Flores, M.D., global head of Medical AI, NVIDIA. “Using the NVIDIA COVID lesion segmentation model available on our NGC software hub, we were able to quickly label the NIH dataset, allowing radiologists to do precise annotations in record time.”

“I applaud the computer science, data science and image processing global academic community for rapidly teaming up to combine multi-disciplinary expertise towards development of potential automated and multi-parametric tools to better study and address the myriad of unmet clinical needs created by the pandemic,” said Bradford Wood, M.D., director, NIH Center for Interventional Oncology and chief, Interventional Radiology Section, NIH Clinical Center. “Thank you to each team for locking arms towards a common cause that unites the scientific community in these challenging times.”

happy children running with kite

Spurring innovation to support pediatric preparedness

happy children running with kite

There are many lessons to be learned from the response to the COVID-19 pandemic, but one that is at the forefront is to be prepared for anything and to strengthen readiness even in the unlikeliest circumstances.

This was the focus of a recent panel discussion featuring Lee Beers, M.D., F.A.A.P, medical director of Community Health and Advocacy within the Goldberg Center for Community Pediatric Health and Child Health Advocacy Institute at Children’s National Hospital. Dr. Beers is also president of the American Academy of Pediatrics.

The webinar entitled, “Protecting Our Future: Spurring Innovation to Support Pediatric Preparedness,” was hosted by Johnson & Johnson Innovation – JLABS (JLABS) as a product of BLUE KNIGHT™, a collaboration between JLABS and the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services.

This event focused on what innovators can do to develop therapeutics, diagnostics, vaccines and other technologies that may protect our future, our children. Experts shared what has been done to develop groundbreaking medical countermeasures that aim to prepare and protect pediatric populations from the health threats of today and those of tomorrow. The main discussions were on ecosystems readiness, adaptations for the pediatric population and the way forward in 2021.

“One size does not fit all for pediatrics when it comes to treatments and personal protective equipment,” said Dr. Beers “We need to know the need and how to do the roll-out.” Fellow panelists agreed.

Dr. Beers went on to say that mental health is the pandemic within the pandemic for our nation’s youth. There are increased cases and severity now for children who struggle to cope with the lockdowns. “We cannot have our children bear the burdens of our challenges.”

After robust questions and answers from everything from the role of artificial intelligence in preparing for future pandemics to the inclusion of families in research and decisions, the panelists walked away with a good feeling about the future with the unprecedented speed of vaccines aimed to counter the effects of the 2020 virus crisis.

The consensus priorities of 2021 should be to develop specifics for children and not just adaptations from adults, with the aim to advance equity, diversity and inclusion in treatment goals, and to build on the success of telemedicine.

Nationally, funding for pediatric research continues to trail efforts targeted for adults. That’s why Children’s National is creating a one-of-a-kind pediatric research and innovation hub. The Children’s National Research & Innovation Campus is set to open in 2021, located on a nearly 12-acre portion of the former Walter Reed Army Medical Center campus. The campus will combine the strengths of Children’s National with those of public and private partners who share the vision of accelerating new discoveries that save and improve the lives of children. At the new campus, breakthrough innovations can more quickly be translated into new treatments and technologies benefitting kids.

Sally Allain, Head of Johnson & Johnson Innovation – JLABS @ Washington, D.C., highlighted the opening of a 32,000 square-foot facility on the Research & Innovation Campus with a residency capacity for up to 50 companies. This will be the first JLABS site anchored with a children’s hospital and research institute working to bring recognition to the need for more early-stage research and innovation in pediatrics for our smallest patients.

The new site will serve as an incubator for pharmaceutical, medical device, consumer and health technology companies, and serve as the hub for BLUE KNIGHT™. BLUE KNIGHT™ aims to stimulate innovation and incubation of technologies that improve health security and response through companies focused on public health threats and emerging infectious diseases. At JLABS @ Washington, DC, companies selected for BLUE KNIGHT™ will have access to the JLABS ecosystem and being a part of the Research & Innovation Campus, as well as fee assistance for certain costs associated with access, mentorship for BARDA, and dedicated equipment for BLUE KNIGHT™ companies.

child receiving COVID test

COVID testing results highlight importance of understanding virus in children

child receiving COVID test

A new study looking at the results of testing children for COVID-19 through a Children’s National Hospital community-based testing site found that one in four patients had a positive test.

A new study looking at the results of testing children for COVID-19 through a Children’s National Hospital community-based testing site found that one in four patients had a positive test. The findings, reported online Dec. 18 in The Journal of Pediatrics, reinforce that children and young adults are impacted by the virus more than originally believed, and that the continued understanding of their role in transmitting COVID-19 is essential to getting the virus under control.

Of the 1,445 patients tested at the specimen collection site for SARS-CoV-2 virus between March 21 and May 16, 2020, the median age was 8 years old, and more than 34% of positive patients were Hispanic, followed by non-Hispanic Black and non-Hispanic white. The daily positivity rate increased over the study period, from 5.4% during the first week to a peak of 47.4% in May. Children and adolescents were referred to the testing site because of risk of exposure or mild symptoms.

“We knew that community-based testing sites were key in minimizing exposure risk to other patients and health care workers, preserving PPE, centralizing specimen collection services, mitigating acute care site overcrowding and informing our community of the burden caused by this disease,” says Joelle Simpson, M.D., medical director of Emergency Preparedness at Children’s National.

Drive-through/walk-up testing sites outside of a traditional acute care setting have emerged around the world to meet the need for testing mildly ill or asymptomatic individuals. In March, Children’s National Hospital opened a drive-up/walk-up location — one of the first exclusively pediatric testing sites for the virus in the U.S. — where primary care doctors in the Washington, D.C., region could refer young patients for COVID-19 specimen collection and testing.

“At first, children were not the target of testing initiatives, but it is clear that making testing available to pediatric patients early was a very important part of the pandemic response,” says Meghan Delaney, D.O., M.P.H., chief of Pathology and Laboratory Medicine at Children’s National. “Not only can children get severe disease, they can be part of positive clusters with the adults they live with. The knowledge we have gained by testing many thousands of children over the pandemic has provided key information.”

Compared with non-Hispanic white children and after adjustments for age, sex and distance of residence from specimen collection site, minority children had a higher likelihood of infection.

“We wanted to identify the features of children tested at this site who did not require acute medical care and be able to compare demographic and clinical differences between patients who tested positive and negative for COVID-19,” says Dr. Simpson.

Patients with COVID-19 exposure and symptoms were more likely to have a positive test than patients without symptoms. This supports contact tracing for symptomatic cases and testing as an important tool in detecting and containing community spread, according to the study’s findings. Although most patients were referred because they lived with a family member with high risk for exposure or infection, this was not associated with positive test results.

“The impact of this virus is broad and affects planning for children, especially as schools and childcare centers work to reopen,” Dr. Simpson says. “In order to guide the development of measures to control the ongoing pandemic, we need better understand the transmission potential of these mildly symptomatic or well children and young adults.”

global connectedness concept illustration

Research partnerships and capacity building in the time of COVID-19

global connectedness concept illustration

“COVID infection anywhere in the world is COVID infection everywhere in the world,” said John Nkengasong, M.Sc., Ph.D., director of the Africa Centers for Disease Control (Africa CDC), during his remarks on the importance of shared science, innovation and diplomacy. Leading experts in global health met virtually on November 13, 2020, to discuss updates in the COVID-19 crisis and lessons learned in Africa. Children’s National Hospital, along with the George Washington University (GW) Institute for Africa Studies and the CNRS-EpiDaPo Lab, sponsored the half-day conference that captured the interest of international attendees committed to examining how best to expand strong and enduring partnerships between U.S. and African scientists, health professionals and research institutes to meet global challenges.

Trust, transparency and communication were common themes of expert panelists that included Elizabeth Bukusi, Ph.D., M.P.H., Kenya Medical Research Institute; Maryam DeLoffre, Ph.D., GW Humanitarian Action Initiative; Peter Kilmarx, M.D., National Institutes of Health (NIH) Fogarty International Center; Enock Motavu, Ph.D., Makerere University in Uganda; Jennifer Troyer, Ph.D., Human Health and Heredity in Africa Program (H3Africa) at NIH; Désiré Tshala-Katumbay, M.D., Ph.D., National Institute of Biomedical Research in Kinshasa; Eric Vilain, M.D., Ph.D., Center for Genetic Medicine Research at Children’s National, with Institute for African Studies Director Jennifer Cooke, and Jonathan LoTempio Jr and D’Andre Spencer of Children’s National as moderators and co-conveners. Read more about the panelists.

The keynote speaker, Nkengasong, updated the group on the massive efforts in bending the COVID-19 disease curve on the African continent which at present has two million cases and 46,000 deaths. This is fewer than many other regions, and Nkengasong attributes this in part to health systems strengthening and capacity building that already occurred with past pandemics like Ebola. He stressed the importance of focusing on the “4 Ps” — population, pathogen, politics and policy — in fighting the pandemic, and the need to ensure that citizens trust their leaders and the public health measures they advance. New endeavors by the Africa CDC include the Pathogen Genomic Initiative, which will help inform research and responses to COVID-19 and other emergent disease threats, and the African COVID-19 Vaccine Development and Access Strategy, which aims to ensure widespread access, delivery and uptake of effective vaccines across Africa. Africa CDC is surging to hotspots as lockdowns ease or shift, and is empowering universities to invest in proactive and, which has helped with the active response success. “Rising tides raise all boats in the sea,” said Nkengasong. He went on to say that there is great power in coordination and cooperation, and science diplomacy and technology are critical to winning the novel coronavirus war.

In a panel on research partnerships, speakers Motavu, Tshala-Katumbay, and Vilain emphasized the global benefits of scientific collaborations in Africa. Africa contains more human genetic variation than any other region of the world, and capturing that diversity in global understanding of the human genome — which is still heavily skewed toward individuals of European ancestry — will be a major factor in global medical advances of the future. And research into relatively localized diseases can lead to breakthroughs in broader understanding on connections between climate variation, environment, nutrition and child health. “The simplistic, localized, nationalist, way of doing science is over,” said Tshala-Katumbay, “and there is no way to go back.” The discipline of science diplomacy will take time for people to grasp, he added, “but it will be crucial for the future generation of scientists to go back.”

A recurring conference theme was that collaboration between countries is crucial for development of better care. Kilmarx told the event participants that in 2019, the National Institutes of Health supported some 1,668 collaborations with African research institutions. Investments in capacity building have yielded impressive results, and today some of Africa’s foremost leaders in science research and public health have received NIH training and support, stating: “If you plant acorns over the decades, you have some mighty oaks.” Bukusi, once such NIH trainee, now is engaged in training a new generation of African researchers and U.S. researchers based in Africa and expanding research partnerships at the Kenya Medical Research Institute.

Troyer showed the successes of the Human Heredity and Health in Africa Initiative, a large consortium that supports a pan-continental network of laboratories that aims to determine disease susceptibility and drug responses. Finally, DeLoffre underscored the need for long-term investments and the value of building local capacities to respond to current crises and anticipate future challenges.

Overall, there was optimism that innovative coalitions are a long-term strength in fighting pandemics and promoting reciprocal learning that will last after the crisis. Science can be a neutral platform that, combined with diplomacy and technology, builds bridges between peoples.

a telehealth video visit with a patient family

Steady rates of patient satisfaction, reimbursement for cardiac telehealth during COVID-19

a telehealth video visit with a patient family

In the first two weeks of COVID-19’s major impact on the U.S., Children’s National Hospital moved most of its subspecialty in-person day-to-day clinics to virtual care. Children’s National Heart Institute was one of the first divisions to offer telehealth visits — in part because the team was an early adopter of telehealth in cardiology for both physician-to-physician consultations and direct-to-patient care, and stood poised to widely implement it.

A poster presentation at the American Heart Association Scientific Sessions 2020 quantified how the rapid transition to direct-to-consumer telehealth services impacted families with children who have congenital heart disease. The findings were presented by first author Kristine Mehrtens, M.S., B.S.N., R.N., C.P.N., clinical manager for the Heart Institute’s Ambulatory Services.

The team found that though in-person cardiology visits decreased during the COVID-19 pandemic, direct-to-patient telehealth visits were able to partially compensate for the sudden drop.

Additionally, payer reimbursement rates for these direct-to-consumer telehealth visits were similar to in-person clinic visits.

”This is exciting as prior to COVID-19  we have seen a lower reimbursement rates for these cardiology direct-to-consumer telehealth visits compared to in-person cardiology clinic visits,” said Ashraf S. Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who has utilized direct-to-consumer telehealth visits since 2016 and is a senior author on the new study.

Patient satisfaction scores for care providers, including the likelihood of recommending a care provider from Children’s National Hospital, was the same for telehealth follow-up visits as it was for in-person clinic visits before the pandemic.

“As a multidisciplinary team, we agreed that diagnostic studies such as echocardiograms were important to include with follow-up visits,” says Mehrtens. “Together we developed a strategy to ensure we could meet the needs of the patients and also safely conduct in-person visits when necessary.”

Why is this important?

The pandemic and the resulting temporary halt to in-person, non-urgent/emergent visits earlier this year put the most vulnerable people with congenital heart disease at high risk for complications or worsening of their existing heart disease because they are unable to follow the recommended schedule for follow-ups.

The readiness of the Children’s Heart Institute team to quickly move to a telehealth platform successfully bridged the gap between in-person visits for some patients, allowing cardiology surveillance to continue safely.

“I am proud of our team of physicians and advanced care providers,” Harahsheh concludes. “We went from three providers (8%) pre-COVID 19 to 31 (79%) providers offering direct-to-consumer telehealth visits during the pandemic.”

What’s next?

Building on previous, smaller studies of telehealth before the pandemic began, the team will continue to conduct research to assess the safety and efficacy of these telehealth visits over time. The increase in patients who are continuing to see their providers for routine follow-ups via telehealth will allow a larger sample for effective study of this care model.

American Heart Association Scientific Sessions 2020
Impact of Telemedicine on Pediatric Cardiac Center’s Ambulatory Response to the 2019 Novel Coronavirus Disease (covid-19) Pandemic
P1692
9:00am – 10:00am
Fri, Nov 13  (CST)

Read additional news stories about cardiology telehealth:

coronavirus

Single institution study finds high rates of cardiac complications in MIS-C

coronavirus

At this year’s AHA Scientific Sessions, cardiologists from Children’s National Hospital presented a poster about an interesting finding in children with MIS-C.

During the height of the pandemic, researchers at Children’s National Hospital discovered that as many as one half of children diagnosed with multisystem inflammatory disease in children (MIS-C) at the hospital developed cardiac complications including coronary artery abnormalities, even when diagnosed and treated promptly.

The data was shared as part of a poster presentation at the American Heart Association Scientific Sessions in November 2020. Though analysis was limited to the data from one institution’s confirmed MIS-C cases, the findings are significant enough to warrant further study.

Interestingly, the authors noted that the high rate of cardiac complications far exceeds the rate of similar issues in children with Kawasaki disease — another pediatric inflammatory syndrome that shares many common symptoms with MIS-C. The two are so similar that immunomodulation therapies successfully deployed in children with MIS-C were based on those developed to treat Kawasaki disease.

Knowledge of common cardiac complications in Kawasaki disease also flagged the need for routine echocardiograms in patients with MIS-C, which helped identify the higher rates of cardiac complications seen in the MIS-C patient population.

“This finding, however, is another data point that shows how MIS-C and Kawasaki disease have some specific differences needing further study,” says Ashraf Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who studies Kawasaki disease and the first author on the new study.

“Previous clinical advancements made in Kawasaki disease set the stage for our response to MIS-C early on,” he said. ”Now we also need to understand MIS-C as its own syndrome so we can better address what we are seeing in this patient population,” he says.

While most of the cardiac findings resolved during follow up, long-term studies are needed to determine if the cardiac abnormalities are associated with major cardiac events later.

“This work will help inform the community of the importance of diagnosing children with MIS-C promptly and following clinical guidelines for necessary tests and treatments once MIS-C is diagnosed,” Harahsheh concludes.

Next, the research team plans to take a deep dive into patient demographics as well as findings from clinical, laboratory and electrocardiogram data for children who developed cardiac complications with MIS-C. The goal will be to refine treatment algorithms and potentially identify a subgroup of patients who may require different or more intense therapy to prevent cardiac complications.

American Heart Association Scientific Sessions 2020 Poster Session
Cardiac Complications of SARS CoV-2 Associated Multi-System Inflammatory Syndrome in Children (MIS-C)
P1306
9:00am – 10:00am
Fri, Nov 13 (CST)

communication network concept image

Children’s National joins international AI COVID-19 initiative

communication network concept image

Children’s National Hospital is the first pediatric partner to join an international initiative led by leading technology firm NVIDIA and Massachusetts General Brigham Hospital, focused on creating solutions through machine and deep learning to benefit COVID-19 healthcare outcomes.

Children’s National Hospital is the first pediatric partner to join an international initiative led by leading technology firm NVIDIA and Massachusetts General Brigham Hospital, focused on creating solutions through machine and deep learning to benefit COVID-19 healthcare outcomes. The initiative, known as EXAM (EMR CXR AI Model) is the largest and most diverse federated learning enterprise, comprised of 20 leading hospitals from around the globe.

Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital, noted that one of the core goals of the initiative is to create a platform which brings resources together, from a variety of leading institutions, to advance the care of COVID-19 patients across the board, including children.

“Children’s National Hospital is proud to be the first pediatric partner joining the world’s leading healthcare institutions in this collaboration to advance global health,” says Linguraru. “We are currently living in a time where rapid access to this kind of global data has never been more important — we need solutions that work fast and are effective. That is not possible without this degree of collaboration and we look forward to continuing this important work with our partners to address one of the most significant healthcare challenges in our lifetime.”

A recent systematic review and meta-analysis from Children’s National Hospital became another core contribution to understanding how children are impacted by COVID-19. Led by Linguraru and accepted to be published in Pediatric Pulmonology, it offers the first comprehensive summary of the findings of various studies published thus far that describe COVID-19 lung imaging data across the pediatric population.

The review examined articles based on chest CT imaging in 1,026 pediatric patients diagnosed with COVID-19, and concluded that chest CT manifestations in those patients could potentially be used to prompt intervention across the pediatric population.

Marius George Linguraru

“Children’s National Hospital is proud to be the first pediatric partner joining the world’s leading healthcare institutions in this collaboration to advance global health,” says Marius George Linguraru, D.Phil., M.A., M.Sc.

“Until this point, pediatric COVID-19 studies have largely been restricted to case reports and small case series, which have prevented the identification of any specific pediatric lung disease patterns in COVID-19 patients,” says Linguraru. “Not only did this review help identify the common patterns in the lungs of pediatric patients presenting COVID-19 symptoms, which are distinct from the signs of other viral respiratory infections in children, it also provided insight into the differences between children and adults with COVID-19.”

Earlier this month, NVIDIA announced the EXAM initiative had – in just 20 days – developed an artificial intelligence (AI) model to determine whether a patient demonstrating COVID-19 symptoms in an emergency room would require supplemental oxygen hours – even days – after the initial exam. This data ultimately aids physicians in determining the proper level of care for patients, including potential ICU placement.

The EXAM initiative achieved a machine learning model offering precise prediction for the level of oxygen incoming patients would require.

In addition to Children’s National Hospital, other participants included Mass Gen Brigham and its affiliated hospitals in Boston; NIHR Cambridge Biomedical Research Centre; The Self-Defense Forces Central Hospital in Tokyo; National Taiwan University MeDA Lab and MAHC and Taiwan National Health Insurance Administration; Tri-Service General Hospital in Taiwan; Kyungpook National University Hospital in South Korea; Faculty of Medicine, Chulalongkorn University in Thailand; Diagnosticos da America SA in Brazil; University of California, San Francisco; VA San Diego; University of Toronto; National Institutes of Health in Bethesda, Maryland; University of Wisconsin-Madison School of Medicine and Public Health; Memorial Sloan Kettering Cancer Center in New York; and Mount Sinai Health System in New York.

antibodies attached to COVID

Study shows COVID-19 antibodies and virus can coexist

antibodies attached to COVID

Children’s National study shows that children can have COVID-19 antibodies and the virus in their system simultaneously.

With many questions remaining around how children spread COVID-19, Children’s National Hospital researchers set out to improve the understanding of how long it takes pediatric patients with the virus to clear it from their systems, and at what point they start to make antibodies that work against the coronavirus. The study, published Sept. 3 in the Journal of Pediatrics, finds that the virus and antibodies can coexist in young patients.

“With most viruses, when you start to detect antibodies, you won’t detect the virus anymore. But with COVID-19, we’re seeing both,” says Burak Bahar, M.D., lead author of the study and director of Laboratory Informatics at Children’s National. “This means children still have the potential to transmit the virus even if antibodies are detected.”

She adds that the next phase of research will be to test if the virus that is present alongside the antibodies can be transmitted to other people. It also remains unknown if antibodies correlate with immunity, and how long antibodies and potential protection from reinfection last.

The study also assessed the timing of viral clearance and immunologic response. It found the median time from viral positivity to negativity, when the virus can no longer be detected, was 25 days. The median time to seropositivity, or the presence of antibodies in the blood, was 18 days, while the median time to reach adequate levels of neutralizing antibodies was 36 days. Neutralizing antibodies are important in potentially protecting a person from re-infection of the same virus.

This study used a retrospective analysis of 6,369 children tested for SARS-CoV-2, the virus that causes COVID-19, and 215 patients who underwent antibody testing at Children’s National between March 13, 2020, and June 21, 2020. Out of the 215 patients, 33 had co-testing for both the virus and antibodies during their disease course. Nine of the 33 showed presence of antibodies in their blood while also later testing positive for the virus.

Also of note, researchers found patients 6 through 15 years old took a longer time to clear the virus (median of 32 days) compared to patients 16 through 22 years old (median of 18 days). Females in the 6-15 age group also took longer to clear the virus than males (median of 44 days for females compared to median of 25.5 days for males).

Although there is emerging data regarding this timing in adults with COVID-19, there is far less data when it comes to the pediatric population. The findings being gathered by Children’s National researchers and scientists around the world are critical to helping understand the unique impact on children and their role in viral transmission.

“The takeaway here is that we can’t let our guard down just because a child has antibodies or is no longer showing symptoms,” says Dr. Bahar. “The continued role of good hygiene and social distancing remains critical.”

Other researchers who contributed to this study include Cyril Jacquot, M.D.; Delores Y Mo,M.D.; Roberta L DeBiasi, M.D.; Joseph Campos, Ph.D.; and Meghan Delaney, D.O.

coronavirus

T-cells show promise to protect vulnerable patients from COVID-19 infection

coronavirus

Children’s National Hospital immunotherapy experts have found that T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function.

Children’s National Hospital immunotherapy experts have found that T-cells taken from the blood of people who recovered from a COVID-19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function. Their findings were published Oct. 26, 2020, in Blood.

“We found that many people who recover from COVID-19 have T-cells that recognize and target viral proteins of SARS-CoV-2, giving them immunity from the virus because those T-cells are primed to fight it,” says Michael Keller, M.D., a pediatric immunology specialist at Children’s National Hospital, who led the study. “This suggests that adoptive immunotherapy using convalescent T-cells to target these regions of the virus may be an effective way to protect vulnerable people, especially those with compromised immune systems due to cancer therapy or transplantation.”

Based on evidence from previous phase 1 clinical trials using virus-targeting T-cells “trained” to target viruses such as Epstein-Barr virus, the researchers in the Cellular Therapy Program at Children’s National hypothesized that the expanded group of COVID-19 virus-targeting T-cells could be infused into immunocompromised patients, helping them build an immune response before exposure to the virus and therefore protecting the patient from a serious or life-threatening infection.

“We know that patients who have immune deficiencies as a result of pre-existing conditions or following bone marrow or solid organ transplant are extremely vulnerable to viruses like SARS-CoV-2,” says Catherine Bollard, M.D., M.B.Ch.B., senior author of the study and director of the novel cell therapies program and the Center for Cancer and Immunology Research at Children’s National. “We’ve seen that these patients are unable to easily clear the virus on their own, and that can prevent or delay needed treatments to fight cancer or other diseases. This approach could serve as a viable option to protect or treat them, especially since their underlying conditions may make vaccines for SARS-CoV-2 unsafe or ineffective.”

The T-cells were predominantly grown from the peripheral blood of donors who were seropositive for SARS-CoV-2. The study also identified that SARS-CoV-2 directed T-cells have adapted to predominantly target specific parts of the viral proteins found on the cell membrane, revealing new ways that the immune system responds to COVID-19 infection.

Current vaccine research focuses on specific proteins found mainly on the “spikes” of the coronavirus SARS-CoV-2. The finding that T-cells are successfully targeting a membrane protein instead may add another avenue for vaccine developers to explore when creating new therapeutics to protect against the virus.

“This work provides a powerful example of how both scientific advances and collaborative relationships developed in response to a particular challenge can have broad and unexpected impacts on other areas of human health,” says Brad Jones, Ph.D., an associate professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine and co-author on the study, whose lab focuses on HIV cure research. “I began working with Dr. Bollard’s team several years ago out of our shared interest in translating her T-cell therapy approaches to HIV. This put us in a position to quickly team up to help develop the approach for COVID-19.”

The Cellular Therapy Program is now seeking approval from the U.S. Food and Drug Administration for a phase 1 trial that will track safety and effectiveness of using COVID-19-specific T-cells to boost the immune response in patients with compromised immune systems, particularly for patients after bone marrow transplant.

illustration of lungs surrounded by virus

COVID-19: First comprehensive review of pediatric lung imaging features

illustration of lungs surrounded by virus

A systematic review and meta-analysis by Children’s National Hospital researchers, published in Pediatric Pulmonology, provides the first comprehensive review of the findings of published studies describing COVID-19 lung imaging data in children.

The number COVID-19 studies focused on children have been small and with limited data. This has prevented the identification of specific pediatric lung disease patterns in COVID-19. Although children make up around 9.5% of COVID-19 infections, less than 2% of the literature on the virus, its symptoms and effects, have focused on kids.

A systematic review and meta-analysis by Children’s National Hospital researchers, published in Pediatric Pulmonology, provides the first comprehensive review of the findings of published studies describing COVID-19 lung imaging data in children. The analysis concludes that chest CT manifestations in children with COVID‐19 could potentially prompt intervention in the pediatric population.

Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, discusses the importance of this work.

Q: What findings stand out to you?

A: We found that more than a third of children with COVID-19 had normal imaging. The lung imaging findings in these children were overall less frequent and less severe than in adult patients, but they were also more heterogeneous than in adults. Importantly, children with COVID-19 were three times more likely to have a normal exam than adults.

Several common lung imaging findings reported in adults were extremely rare or not found in the pediatric studies. These discoveries, and other recent reports in this space, support the fact that children’s symptoms may be less obvious than adults or even absent, but they still carry the virus and may be at risk for serious and life-threatening illness.

Marius George Linguraru

Marius George Linguraru, D.Phil., M.A., M.Sc., principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National.

Q: How will the findings of this study benefit pediatric care?

A: In our study, we showed how the health of the lungs of these children is impacted. Our results from data from 1,026 children (from newborns to 18 year old) with COVID-19 present chest manifestations that could potentially prompt informed intervention and better recovery.

Another conclusion of our study is that the abnormalities reported on the chest scans of children infected with COVID-19 are distinct from the typical lung images seen during other viral respiratory infections in the pediatric population. This is important for preparing for the cold and flu season.

Q: Why was this review important to our understanding of how COVID-19 impacts children?

A: This is the first systematic review and meta-analysis focused on the manifestation of the COVID-19 infection in the lungs of children. Our study, and others from colleagues at Children’s National, helps lead the efforts on elucidating how the pandemic affects the health of children.

Though children were initially thought to be less susceptible to infection, the data has made it clear that many children are at high risk for hospitalization and severe health complications. Although there are similarities between how children and adults are affected by the pandemic, there are also critical differences.

Given the limited knowledge in the manifestation of COVID-19 in children, with children susceptible to infection and hospitalization, and with children returning to school, continued efforts to understand the impact of COVID-19 on young patients is critically important. Understanding how children fare through the pandemic is the foundation of discovering better ways to take care of young patients and their health.

You can find the full study published in Pediatric Pulmonology. Learn more about the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National.

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.

COVID-19 triage tent outside the hospital Emergency Department

Telehealth team shares its pandemic response and discusses the future of telehealth

COVID-19 triage tent outside the hospital Emergency Department

The telehealth team at Children’s National Hospital is featured in DataBank IMX’s latest Tech Talk podcast. They discuss how the organization scaled up and managed the telehealth program through the early and mid phases of the COVID-19 pandemic, as well as the future of telehealth.

Featured in the discussion are clinical, operational and revenue cycle leaders from Children’s National:

  • Mary Daymont, M.S.N., R.N., CCM, Vice President, Revenue Cycle & Care Management
  • Clarence Williams, MHA, MBA, Director, Telehealth Program
  • Alejandro Lopez-Magallon, M.D., Medical Director, Telehealth Program, Cardiac Critical Care Specialist

tech talk

sick boy in bed

Clinical features of COVID-19 versus influenza

sick boy in bed

In a cohort retrospective study comparing clinical features of COVID-19 and seasonal flu, researchers found surprisingly little difference in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups.

As the fall approaches, pediatric hospitals will start seeing children with seasonal influenza A and B. At the same time, COVID-19 will be co-circulating in communities with the flu and other respiratory viruses, making it more difficult to identify and prevent the novel coronavirus.

With little published data directly comparing the clinical features of children with COVID-19 to those with seasonal flu, researchers at Children’s National Hospital decided to conduct a retrospective cohort study of patients in the two groups. Their findings — published September 8 in JAMA Network Open — surprised them.

The study — detailed in the article “Comparison of Clinical Features of US Children With COVID-19 vs Seasonal Influenza A and B” — showed no statistically significant differences in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups.

The other unexpected finding was that more patients with COVID-19 than those with seasonal influenza reported fever, cough, diarrhea or vomiting, headache, body ache or chest pain at the time of diagnosis, says Xiaoyan Song, Ph.D., M.Sc., M.B., the study’s principal investigator.

“I didn’t see this coming when I was thinking about doing the study,” says Dr. Song, director of Infection Control and Epidemiology at Children’s National since 2007 and a professor of pediatrics at the George Washington University School of Medicine and Health Sciences. “It took several rounds of thinking and combing through the data to convince myself that this was the conclusion.”

Given that much remains unknown about COVID-19, the researchers’ discovery that children with the disease present with more symptoms at the time of diagnosis is a valuable one.

“It’s a good cue from a prevention and planning perspective,” says Dr. Song. “We always emphasize early recognition and early isolation with COVID. Having a clinical picture in mind will assist clinicians as they diagnose patients with symptoms of the coronavirus.”

The study included 315 children who were diagnosed with a laboratory-confirmed COVID-19 between March 25, 2020, and May 15, 2020, and 1,402 children who were diagnosed with a laboratory-confirmed seasonal influenza between Oct. 1, 2019, and June 6, 2020, at Children’s National. Asymptomatic patients who tested positive for COVID-19 during pre-admission or pre-procedural screening were excluded from the study.

Of the 315 patients who tested positive for COVID-19, 52% were male, with a median age of 8.4 years. Of these patients, 54 (17.1 %) were hospitalized, including 18 (5.7%) who were admitted to the intensive care unit (ICU) and 10 (3.2%) who received mechanical ventilator treatment.

Among the 1,402 patients who tested positive for influenza A or B, 52% were male, with a median age of 3.9 years, and 291 (21.2%) were hospitalized, including 143 for influenza A and 148 for influenza B. Ninety-eight patients (7.0%) were admitted to the ICU, and 27 (1.9%) received mechanical ventilator support.

The study showed a slight difference in the age of children hospitalized with COVID-19 compared to those hospitalized with seasonal influenza. Patients hospitalized with COVID-19 had a median age of 9.7 years vs. those hospitalized with seasonal influenza who had a median age of 4.2 years.

In both groups, fever was the most often reported symptom at the time of diagnosis followed by cough. A greater proportion of patients hospitalized with COVID-19 than those hospitalized with seasonal influenza reported fever (76% vs. 55%), cough (48% vs. 31%), diarrhea or vomiting (26% vs. 12%), headache (11% vs. 3%), body ache/myalgia (22% vs. 7%), and chest pain (11% vs. 3%).

More patients hospitalized with COVID-19 than those with seasonal influenza reported sore throat or congestion (22% vs. 20%) and shortness of breath (30% vs. 20%), but the differences were not statistically significant.

During the study period, the researchers noticed an abrupt decline of influenza cases at Children’s National after local schools closed in mid-March and stay-at-home orders were implemented about two weeks later to combat the community spread of COVID-19. Dr. Song says the impact of school closures on the spread of COVID-19 among children is the next area of study for her research team.

“We want to assess the quantitative impact of school closures so we can determine at what point the cost of closing schools and staying at home outweighs the benefit of reducing transmission of COVID-19 and burdens on the health care system,” she says.

Dr. Song urges members of the community “first and foremost to stay calm and be strong. We’re learning new and valuable things about this virus each day, which in turn improves care. The collision of the flu and COVID-19 this fall could mean an increase in pediatric hospitalizations. That’s why it’s important to get your flu shot, because it can help take at least one respiratory virus out of circulation.”

Other researchers who contributed to this study include Meghan Delaney, D.O.; Rahul K. Shah, M.D.; Joseph M. Campos, Ph.D.; David L. Wessel, M.D.; and Roberta L. DeBiasi, M.D.

young boy and teddy bear in face masks

Study provides important insight into spread of COVID-19 in children

young boy and teddy bear in face masks

New research suggests that children can shed SARS-CoV-2, the virus that causes COVID-19, even if they never develop symptoms or for long after symptoms have cleared. But many questions remain about the significance of the pediatric population as vectors for this sometimes deadly disease.

New research suggests that children can shed SARS-CoV-2, the virus that causes COVID-19, even if they never develop symptoms or for long after symptoms have cleared. But many questions remain about the significance of the pediatric population as vectors for this sometimes deadly disease, according to an invited commentary by Children’s National Hospital doctors that accompanies this new study published online Aug. 28, 2020 in JAMA Pediatrics. The commissioned editorial, written by Roberta L. DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases, and Meghan Delaney, D.O., M.P.H., chief of the Division of Pathology and Lab Medicine, provides important insight on the role children might play in the spread of COVID-19 as communities continue to develop public health strategies to reign in this disease.

The study that sparked this commentary focused on 91 pediatric patients followed at 22 hospitals throughout South Korea. “Unlike in the American health system, those who test positive for COVID-19 in South Korea stay at the hospital until they clear their infections even if they aren’t symptomatic,” explains Dr. DeBiasi.

The patients here were identified for testing through contact tracing or developing symptoms. About 22% never developed symptoms, 20% were initially asymptomatic but developed symptoms later, and 58% were symptomatic at their initial test. Over the course of the study, the hospitals where these children stayed continued to test them every three days on average, providing a picture of how long viral shedding continues over time.

The study’s findings show that the duration of symptoms varied widely, from three days to nearly three weeks. There was also a significant spread in how long children continued to shed virus and could be potentially infectious. While the virus was detectable for an average of about two-and-a-half weeks in the entire group, a significant portion of the children — about a fifth of the asymptomatic patients and about half of the symptomatic ones — were still shedding virus at the three week mark.

Drs. DeBiasi and Delaney write in their commentary that the study makes several important points that add to the knowledge base about COVID-19 in children. One of these is the large number of asymptomatic patients — about a fifth of the group followed in this study. Another is that children, a group widely thought to develop mostly mild disease that quickly passes, can retain symptoms for weeks. A third and important point, they say, is the duration of viral shedding. Even asymptomatic children continued to shed virus for a long time after initial testing, making them potential key vectors.

However, the commentary authors say, despite these important findings, the study raises several questions. One concerns the link between testing and transmission. A qualitative “positive” or “negative” on testing platforms may not necessarily reflect infectivity, with some positives reflecting bits of genetic material that may not be able to make someone sick or negatives reflecting low levels of virus that may still be infectious.

Testing reliability may be further limited by the testers themselves, with sampling along different portions of the respiratory tract or even by different staff members leading to different laboratory results. It’s also unknown whether asymptomatic individuals are shedding different quantities of virus than those with symptoms, a drawback of the qualitative testing performed by most labs. Further, testing only for active virus instead of antibodies ignores the vast number of individuals who may have had and cleared an asymptomatic or mild infection, an important factor for understanding herd immunity.

Lastly, Drs. DeBiasi and Delaney point out, the study only tested for viral shedding from the respiratory tract even though multiple studies have detected the virus in other bodily fluids, including stool. It’s unknown what role these other sources might play in the spread of this disease.

Drs. DeBiasi and Delaney note that each of these findings and additional questions could affect public health efforts continually being developed and refined to bring COVID-19 under control in the U.S. and around the world. Children’s National has added their own research to these efforts, with ongoing studies to assess how SARS-CoV-2 infections proceed in children, including how antibodies develop both at the individual and population level.

“Each of these pieces of information that we, our collaborators and other scientists around the world are working to gather,” says Dr. DeBiasi, “is critical for developing policies that will slow the rate of viral transmission in our community.”

coronavirus

Higher COVID-19 rates seen in minority socioeconomically disadvantaged children

coronavirus

Minority and socioeconomically disadvantaged children have significantly higher rates of COVID-19 infection, a new study led by Children’s National Hospital researchers shows.

Minority and socioeconomically disadvantaged children have significantly higher rates of COVID-19 infection, a new study led by Children’s National Hospital researchers shows. These findings, reported online August 5 in Pediatrics, parallel similar health disparities for the novel coronavirus that have been found in adults, the authors state.

COVID-19, an infection caused by the novel coronavirus SARS-CoV-2 that emerged in late 2019, has infected more than 4.5 million Americans, including tens of thousands of children. Early in the pandemic, studies highlighted significant disparities in the rates of infection in the U.S., with minorities and socioeconomically disadvantaged adults bearing much higher burdens of infection. However, says Monika Goyal, M.D., M.S.C.E, a pediatric emergency medicine specialist and associate division chief in the Division of Emergency Medicine at Children’s National whose research focuses on health disparities, it’s been unclear whether these disproportionate rates of infection also extend to youth.

To investigate this question, she and her colleagues looked to data collected between March 21, 2020, and April 28, 2020, from a drive-through/walk-up COVID-19 testing site affiliated with Children’s National — one of the first exclusively pediatric testing sites for the virus in the U.S. To access this free testing site, funded by philanthropic support, patients between the ages of 0 and 22 years needed to meet specific criteria: mild symptoms and either known exposure, high-risk status, family member with high-risk status or required testing for work. Physicians referred patients through an online portal that collected basic demographic information, reported symptoms and the reason for referral.

When Dr. Goyal and her colleagues analyzed the data from the first 1,000 patients tested at this site, they found that infection rates differed dramatically among different racial and ethnic groups. While about 7% of non-Hispanic white children were positive for COVID-19, about 30% of non-Hispanic Black and 46% of Hispanic children were positive.

“You’re going from about one in 10 non-Hispanic white children to one in three non-Hispanic Black children and one in two Hispanic children. It’s striking,” says Dr. Goyal.

Using data from the American Families Survey, which uses five-year census estimates derived from home address to estimate median family income, the researchers separated the group of 1,000 patients into estimated family income quartiles. They found marked disparities in COVID-19 positivity rates by income levels: while those in the highest quartile had infection rates of about 9%, about 38% of those in the lowest quartile were infected.

There were additional disparities in exposure status, Dr. Goyal adds. Of the 10% of patients who reported known exposure to COVID-19, about 11% of these were non-Hispanic white. However, non-Hispanic Black children were triple this number.

Although these numbers show clear disparities in COVID-19 infection rates, the authors are now trying to understand why these disparities occur and how they can be mitigated.

“Some possible reasons may be socioeconomic factors that increase exposure, differences in access to health care and resources, as well as structural racism,” says Dr. Goyal.

She adds that Children’s National is working to address those factors that might increase risk for COVID-19 infection and poor outcomes by helping to identify unmet needs — such as food and/or housing insecurity — and steer patients toward resources when patients receive their test results.

“As clinicians and researchers at Children’s National, we pride ourselves on not only being a top-tier research institution that provides cutting-edge care to children, but by being a hospital that cares about the community we serve,” says Denice Cora-Bramble, M.D., M.B.A., chief medical officer of Ambulatory and Community Health Services at Children’s National and the research study’s senior author. “There’s still so much work to be done to achieve health equity for children.”

Other Children’s National researchers who contributed to this study include Joelle N. Simpson, M.D.; Meleah D. Boyle, M.P.H, Gia M. Badolato, M.P.H; Meghan Delaney, D.O,. M.P.H.; and Robert McCarter Jr., Sc.D.

The science-policy interface

We can do better: Lessons learned on COVID-19 data sharing can inform future outbreak preparedness

Since COVID-19 emerged late last year, there’s been an enormous amount of research produced on this novel coronavirus disease. But the content publicly available for this data and the format in which it’s presented lack consistency across different countries’ national public health institutes, greatly limiting its usefulness, Children’s National Hospital scientists report in a new study. Their findings and suggestions, published online August 19 in Science & Diplomacy, could eventually help countries optimize their COVID-19-related data — and data for future outbreaks of other diseases — to help further new research, clinical decisions and policy-making around the world.

Recently, explains study senior author Emmanuèle Délot, Ph.D., research faculty at Children’s National Research Institute, she and her colleagues sought data on sex differences between COVID-19 patients around the world for a new study. However, she says, when they checked the information available about different countries, they found a startling lack of consistency, not only for sex-disaggregated data, but also for any type of clinical or demographic information.

“The prospects of finding the same types of formats that would allow us to aggregate information, or even the same types of information across different sites, was pretty dismal,” says Dr. Délot.

To determine how deep this problem ran, she and colleagues at Children’s National, including Eric Vilain, M.D., Ph.D., the James A. Clark Distinguished Professor of Molecular Genetics and the director of the Center for Genetic Medicine Research at Children’s National, and Jonathan LoTempio, a doctoral candidate in a joint program with Children’s National and George Washington University, surveyed and analyzed the data on COVID-19.

The research spanned data reported by public health agencies from highly COVID-19 burdened countries, viral genome sequence data sharing efforts, and data presented in publications and preprints.

PubMed entries with coronavirus

Publications with the term “coronavirus” archived in PubMed over time.

At the time of study, the 15 countries with the highest COVID-19 burden at the time included the US, Spain, Italy, France, Germany, the United Kingdom, Turkey, Iran, China, Russia, Brazil, Belgium, Canada, the Netherlands and Switzerland. Together, these countries represented more than 75% of the reported global cases. The research team combed through COVID-19 data presented on each country’s public health institute website, looking first at the dashboards many provided for a quick glimpse into key data, then did a deeper dive into other data on this disease presented in other ways.

The data content they found, says LoTempio, was extremely heterogeneous. For example, while most countries kept running totals on confirmed cases and deaths, the availability of other types of data — such as the number of tests run, clinical aspects of the disease such as comorbidities, symptoms, or admission to intensive care, or demographic information on patients, such as age or sex — differed widely among countries.

Similarly, the format in which data was presented lacked any consistency among these institutes. Among the 15 countries, data was presented in plain text, HTML or PDF. Eleven offered an interactive web-based data dashboard, and seven had comma-separated data available for download. These formats aren’t compatible with each other, LoTempio explains, and there was little to no documentation about where the data that supplies some formats — such as continually updated web-based dashboards — was archived.

The science-policy interface

Graphic representation of the science-policy interface.

Dr. Vilain says that a robust system is already in place to allow uniform sharing of data on flu genomes — the World Health Organization’s (WHO) Global Initiative on Sharing All Influenza Data (GISAID) — which has been readily adapted for the virus that causes COVID-19 and has already helped advance some types of research. However, he says, countries need to work together to develop a similar system for harmonized sharing other types of data for COVID-19. The study authors recommend that COVID-19 data should be shared among countries using a standardized format and standardized content, informed by the success of GISAID and under the backing of the WHO.

In addition, the authors say, the explosion of research on COVID-19 should be curated by experts who can wade through the thousands of papers published on this disease since the pandemic began to identify research of merit and help merge clinical and basic science.

“Identifying the most useful science and sharing it in a way that’s usable to most researchers, clinicians and policymakers, will not only help us emerge from COVID-19 but could help us prepare for the next pandemic,” Dr. Vilain says.

Other researchers who contributed to this study include D’Andre Spencer, MPH, Rebecca Yarvitz, BA, and Arthur Delot-Vilain.

mother measuring sick child's temperature

Connections between Kawasaki disease and MIS-C

mother measuring sick child's temperature

A new review article enumerates some key similarities and differences between MIS-C and Kawasaki disease.

Since May 2020, there has been some attention in the general public and the news media to a specific constellation of symptoms seen in children with COVID-19 or who have been exposed to COVID-19. For a time, headlines even called it a “Kawasaki-like” disease. At first glance, both the symptoms and the effective treatments are remarkably similar. However, a new review published in Trends in Cardiovascular Medicine finds that under closer scrutiny, the two conditions have some interesting differences as well.

“At the beginning of this journey, we thought we might be missing actual cases of Kawasaki disease because we identified a few patients who presented late and developed coronary artery abnormalities,” says Ashraf Harahsheh, M.D., senior author of the review article, “Multisystem inflammatory syndrome in children: Is there a linkage to Kawasaki disease?” and a cardiologist at Children’s National Hospital. “But as time passed, children exposed to COVID-19 started to present with a particular constellation of symptoms that actually had some important similarities and distinctions from Kawasaki.”

Similarities between Kawasaki disease and MIS-C

Both disease patterns seem to have a common trigger that provokes the inflammatory cascade reaction in genetically susceptible children, the authors write. However, there is also early evidence that children with each disease have different genetic markers, meaning different populations are genetically susceptible to each disease.

Additionally, the authors found that the massive activation of pro-inflammatory cytokines seen in MIS-C, also known as a “cytokine storm,” overlaps with a similar occurrence seen in Kawasaki disease, adult COVID-19 patients, toxic shock syndrome and some other viral infections.

Primary differences between Kawasaki disease and MIS-C

Overall, when compared to Kawasaki disease, children with MIS-C tend to:

  • Present at an older age
  • Have a more profound form of inflammation
  • Have more gastrointestinal manifestation
  • Show different laboratory findings
  • Have greater risk of left ventricle dysfunction and shock

Further study of both Kawasaki and MIS-C needed

Despite noted differences, the authors are also careful to credit the documented similarities between Kawasaki disease and MIS-C as a key to the quick identification of the new syndrome in children. The study of Kawasaki disease also gave clinicians a valid basis to begin developing diagnostic recommendations and treatment protocols.

The review’s first author Yue-Hin Loke, M.D., who is also a cardiologist at Children’s National, says, “The quick recognition of MIS-C is only possible because of meticulous research conducted by Dr. Tomisaku Kawasaki, who recently passed away on June 5th, 2020. Even though some aspects of both are still shrouded in mystery, the previous research and clinical advancements made in Kawasaki disease set the stage for our immediate response to MIS-C.”

“Previous research provided key information for cardiologists facing this new syndrome, including the necessity of routine echocardiograms to watch for coronary artery abnormalities (CAAs) and for use of  intravenous immunoglobulin (IVIG) to mitigate  the development of CAAs,” says Charles Berul, M.D., chief of Cardiology at Children’s National and a co-author. “Both of these factors have played a key role in reducing the mortality of MIS-C to almost zero.”

The authors note that more research is needed to understand both Kawasaki disease and the specifics of MIS-C, but that what is learned about the mechanisms of one can and should inform study and treatment of the other. And in the meantime, caution and continued surveillance of these patients, especially with respect to coronary artery and myocardial function, will continue to improve the long-term outcomes for both syndromes.