Infectious Disease Archives

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

February 8, 2021

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.

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.

Advance care planning and the trajectory of end-of-life treatment preference

February 5, 2021

Advance care planning is a process that helps patients define their goals, values and preferences for future medical care. This information is shared with a surrogate decision maker who will make decisions for the patient if/when they are unable to make decisions for themselves. While ongoing conversations with the surrogate about goals of care are recommended, the optimal timing has not been empirically determined, until now.

Maureen Lyon, Ph.D., and her colleagues at Children’s National Hospital found that adults living with HIV and their chosen surrogate decision makers, who participated in a FAmily CEntered (FACE) advance care planning intervention, had seven times the odds of being on the same page about end of life decisions compared with controls. The researchers’ 5-year randomized clinical trial conducted in Washington, D.C., highlights a critical period 3 months after the intervention which might be optimal to schedule a booster session. FACE advance care planning had a significant effect on both surrogates’ longitudinal preparedness and confidence in decision-making and understanding of the patients’ end of life treatment preferences, compared to controls. These findings confirm advance care planning is beneficial and support African Americans’ desire to have family participate in decision making.

Children’s National researchers who contributed to this study include Maureen Lyon, Ph.D., Lawrence D’Angelo, M.D., MPH, Jichuan Wang, Ph.D., and Isabella Greenberg, MPH.

Read the full study in the American Journal of Hospice and Palliative Care.

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

January 12, 2021

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:

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

Lee Beers, M.D., F.A.A.P, begins term as AAP president

January 4, 2021

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

Causes, diagnosis and management of acute flaccid myelitis

December 23, 2020

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. Children’s National Hospital was part of a multi-center study focused on AFM and published in The Lancet.

Children’s National authors include Elizabeth Wells, M.D., director of Inpatient Neurology; Jessica Carpenter, M.D., director of the Neonatal and Childhood Stroke Program and co-director of the Neurocritical Care Program; and Roberta DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases.

This review describes the epidemiology, clinical features, course and outcomes of AFM to help to guide diagnosis, management and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral and immunological features of affected patients, host-virus interactions and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

COVID testing results highlight importance of understanding virus in children

December 21, 2020

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.”

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

November 13, 2020

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)

Boeing gives $5 million to support Research & Innovation Campus

November 5, 2020

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.

“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”

The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.

“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”

Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.

The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.

Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.

Children’s National joins international AI COVID-19 initiative

October 28, 2020

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.

“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.

Study shows COVID-19 antibodies and virus can coexist

October 27, 2020

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.

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

October 26, 2020

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.

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

October 19, 2020

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, 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.

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

October 2, 2020

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

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

October 2, 2020

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

Clinical features of COVID-19 versus influenza

September 24, 2020

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.

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

September 15, 2020

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.”

Higher COVID-19 rates seen in minority socioeconomically disadvantaged children

September 10, 2020

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.

Dr. Youssef Kousa awarded Pediatric Epilepsy Research Grant

August 31, 2020

The Child Neurology Foundation has awarded Youssef A. Kousa, M.S., D.O., Ph.D., the 2020 Pediatric Epilepsy Research Foundation Shields Research Grant. The funds will support his work on identifying genetic risk factors in congenital Zika syndrome.

The Child Neurology Foundation has awarded Youssef A. Kousa, M.S., D.O., Ph.D., physician-scientist within the Division of Neurology at Children’s National Hospital, and founder and director of the Zika Genetics Consortium, the 2020 Pediatric Epilepsy Research Foundation Shields Research Grant. The funds will support his work on identifying genetic risk factors in congenital Zika syndrome.

This prestigious grant provides $100,000 of research funding to help identify treatments and cures for pediatric neurologic diseases. It will allow Dr. Kousa to test the hypothesis that rare genetic variants in individuals contributed to being affected with congenital Zika syndrome and the severity of the phenotype for those who were affected.

“Despite decades of research, identifying those at greatest risk of congenital infection or being severely affected remains an elusive goal,” says Dr. Kousa. “This research is important because identifying genetic risk or protective factors for developmental brain malformations can help teach us how the brain develops.”

In 2015, Dr. Kousa established the Zika Genetic Consortium to investigate whether maternal and fetal genetic factors can modify the risk of brain injury from congenital infections.

Dr. Kousa adds that this work will provide key insights into maternal and fetal genetic factors that can contribute to brain malformations. The hope is that these insights may one day translate into targeted prevention efforts.

“Dr. Kousa’s project is very creative and has a fantastic opportunity to look at factors of Zika on brain development,” says William D. Gaillard, M.D., division chief of both Epilepsy and Neurophysiology, and Neurology at Children’s National. “This is a very competitive award. It’s a tremendous achievement that few accomplish.”

Children’s National is the leading site for this international research study.

In 2015, Dr. Kousa established the Zika Genetic Consortium to investigate whether maternal and fetal genetic factors can modify the risk of brain injury from congenital infections. Dr. Kousa is the principal investigator of the consortium, which includes 19 co-investigators representing 13 different institutions.

The consortium is bringing together cohorts of 12,000 mother-infant participants retrospectively and prospectively. These cohorts come from 15 international health centers in seven countries in collaboration with partners at the National Institutes of Health, and the Centers for Disease Control and Prevention.

“This support gives us the opportunity to test our hypothesis,” says Dr. Kousa. “We also hope what we continue to learn about Zika can play a role in helping us understand other congenital infections and neurodevelopment diseases.”

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

August 25, 2020

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.

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.

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.

Case report highlights importance of antibiotic stewardship

August 10, 2020

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well.

A recent meningitis case treated at Children’s National Hospital raises serious concerns about a rise in antibiotic resistance in the common bacterium that caused it, researchers from the hospital write in a case report. Their findings, published online August 3 in the Journal of the Pediatric Infectious Disease Society, could change laboratory and clinical practice across the U.S. and potentially around the globe.

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well, say case report authors Gillian Taormina, D.O., a third year fellow in Pediatric Infectious Diseases at Children’s National, who was on service for this recent case, and Joseph Campos, Ph.D., D(ABMM), FAAM, director of the Microbiology Laboratory and the Infectious Diseases Molecular Diagnostics Laboratory at Children’s National. As standard clinical practice in the U.S., they explain, patients who are thought to have this infection are typically treated first with the broad spectrum antibiotic ceftriaxone while they wait for a microbiology lab to identify the causative organism from blood or cerebrospinal fluid samples. Once the organism is identified as N. meningitidis, patients are typically treated with penicillin or ampicillin, antibiotics with a narrower spectrum of activity that’s less likely to lead to ceftriaxone resistance. Family members and other close contacts are often prophylactically treated with an antibiotic called ciprofloxacin.

Because N. meningitidis has historically been sensitive to these antibiotics, most laboratories do not perform tests to confirm drug susceptibility, Dr. Campos says. But the protocol at Children’s National is to screen these isolates for penicillin and ampicillin resistance with a rapid 5-minute test. The isolate from Dr. Taormina’s five-month-old patient – a previously healthy infant from Maryland who came to the Children’s National emergency room after six days of fever and congestion – yielded surprising results: N. meningitidis grown from the patient’s blood was positive for beta-lactamase, an enzyme that destroys the active component in the family of antibiotics that includes penicillin and ampicillin. This isolate was also found resistant to ciprofloxacin.

“The lab used a rapid test, and after just a few minutes, it was positive,” Dr. Campos says. “We did it again to make sure it was accurate, and the results were reproducible. That’s when we knew we needed to share this finding with the public health authorities.”

Dr. Campos, Dr. Taormina and their colleagues sent samples of the antibiotic-resistant bacteria first to the Washington, D.C. Public Health Laboratory and the Maryland Department of Health, and later to the Centers for Disease Control and Prevention (CDC). When the CDC asked other state laboratories to send their own N. meningitidis samples to be tested, 33 were positive for beta-lactamase. And like the bacterium isolated from Dr. Taormina’s patient, 11 of these were also resistant to ciprofloxacin.

“These bacteria wouldn’t have been susceptible to the common antibiotics that we would normally use for this infection,” Dr. Taormina says, “so it’s entirely possible that the infections caused by these bacteria could have been treated inappropriately if doctors used the standard protocol.”

Dr. Taormina says that her patient cleared his infection after staying on ceftriaxone, the original antibiotic he’d been prescribed, for the recommended seven days. His six family members and close contacts were prophylactically treated with rifampin instead of ciprofloxacin.

Although this case had a positive outcome, Dr. Campos says it raises the alarm for other N. meningitidis infections in the U.S., where antibiotic resistance is a growing concern. The danger is even higher in other countries, where the vaccine that children in the U.S. commonly receive for N. meningitidis at age 11 isn’t available.

In the meantime, Drs. Taormina and Campos say their case highlights the need for the appropriate use of antibiotics, known as antibiotic stewardship, which is only possible with close partnerships between infectious disease doctors and microbiology laboratories.

“Our lab and the infectious diseases service at Children’s National interact every day on cases like this to make sure we’re doing the best job we can in diagnosing and managing infections,” says Dr. Campos. “We’re a team.”

Other Children’s National authors who contributed to this case report include infectious disease specialist Benjamin Hanisch, M.D.