Tag Archive for: DeBiasi

borrelia bacteria

First-of-its-kind study on impacts of Lyme disease in pregnancy and infant development

borrelia bacteria

Lyme disease is caused by the bacterium Borrelia burgdorferi.

Understanding the effects of Lyme disease on the developing fetal brain is essential to ensure timely prenatal and postnatal treatments to protect the fetus and newborn. In response to this need, Children’s National Hospital is leading a pilot study to establish the groundwork needed for a larger study to determine the effect of in utero exposure to Lyme disease on pregnancy and early childhood neurodevelopmental outcomes.

Why it’s important

“Insect-borne illnesses have more than doubled during the last twenty years as a result of multiple factors including environmental changes,” says Sarah Mulkey, M.D., Ph.D., principal investigator of the study and prenatal-neonatal neurologist at Children’s National Hospital. Dr. Mulkey is the Co-Director of the Congenital Infection Program at Children’s National Hospital and has led a long-term child outcome study of the mosquito-borne Zika virus infection in pregnancy and impacts on child neurodevelopment. She is now adding Lyme disease to her work on pregnancy and child outcomes. Lyme disease is transmitted to humans via an infected tick and can be acquired throughout much of the United States. “Very little is known about Lyme disease in pregnancy and if and how it may affect the fetus and impact child neurodevelopment,” said Dr. Mulkey.

This pilot study is funded by the Clinical Trials Network for Lyme and other Tickborne Diseases (CTN), supported by the Steven and Alexandra Cohen Foundation. Roberta DeBiasi, M.D., M.S., division chief of infectious diseases at Children’s National, is a CTN Node Principal Investigator. The study team at Children’s National works closely with members of the CTN as well as other Lyme disease-focused organizations and nonprofits to make sure that the pilot study addresses Lyme disease advocates’ research priorities in a scientifically rigorous way. “This is an important opportunity for us to engage with advocacy groups and others who have been stressing the need for this type of research for decades,” says Meagan Williams, M.S.P.H., C.C.R.C., the senior research coordinator for the study. “We know how important it is to maintain a patient-centered and trauma-sensitive lens in our work with families impacted by Lyme disease during pregnancy. We’ve been working hard to build this study in a way that centers our participants’ lived experiences and focuses on the topics they find important. We’re very grateful to have the support of Lyme disease focused organizations and advocates as we embark on this study because they know and have expressed exactly where the gaps are in the literature. It’s our job to do the work to fill those gaps.”

The big picture

This pilot study aims to build upon existing research, case studies and advocacy to assess developmental and other family impacts of Lyme disease exposure during pregnancy.

Especially as tick season begins in Washington, D.C., and surrounding regions, the investigators are determined to make sure that all eligible people diagnosed with Lyme disease during their pregnancy are aware of the study and have the opportunity to participate. Pregnant volunteers can sign up for participation in the study here. Volunteers may be eligible to join if they are currently pregnant, live in the U.S. or Canada and were diagnosed with Lyme disease during pregnancy or have post-treatment Lyme disease syndrome (PTLDS).

Anyone interested in sharing information about the study with their clients or colleagues may email mewilliams@childrensnational.org for access to the team’s recruitment toolkit that includes flyers, FAQs and other resources. “We have resources available for clinicians, public health professionals, friends and family members and anyone else who may be able to help us identify participants and spread the word about this important study,” Williams says.

The study is registered on ClinicalTrials.gov (NCT06026969). If you have questions about the study, please reach out to Meagan at mewilliams@childrensnational.org or email cnhlymestudy@gmail.com.

Roberta Debiasi

Roberta L. DeBiasi, M.D., M.S., named as Robert H. Parrott Professor of Pediatric Research

Roberta Debiasi

“This wonderful honor will greatly benefit the work of our Infectious Disease Division, and I look forward to working to utilize it to its full potential,” says Dr. DeBiasi.

Children’s National Hospital named Roberta L. DeBiasi, M.D., M.S., as the Robert H. Parrott Professor of Pediatric Research at Children’s National Hospital.

Dr. DeBiasi is chief of the Division of Pediatric Infectious Diseases at Children’s National. She leads the hospital’s response to emerging and highly contagious diseases and co-leads the Children’s National Congenital Infection Program. Dr. DeBiasi is a Principal Investigator in the Center for Translational Research at Children’s National Research Institute. She is a tenured Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine at George Washington University.

About the award

Professorships at Children’s National support groundbreaking work on behalf of children and their families and foster new discoveries and innovations in pediatric medicine. These appointments carry prestige and honor that reflect the recipient’s achievements and donor’s forethought to advance and sustain knowledge. The Robert H. Parrott Professorship in Pediatric Research is one of 47 endowed chairs at Children’s National.

Dr. DeBiasi leads a multidisciplinary team of experts caring for children with infectious diseases and tracking disease transmission to help limit spread and prevent outbreaks. The Division of Pediatric Infectious Diseases is a key referral center in the Washington, D.C., area, helping thousands of patients each year. The division also promotes prevention through community outreach and education.

Dr. DeBiasi’s wide-ranging research portfolio includes studies and clinical trials focused on COVID-19, MIS-C, influenza, Ebola, Lyme disease, Zika and other infections affecting pregnant women, newborns and children. She is the institutional lead of the Lyme Clinical Trials Network, and Principal Investigator for a study focused on long term outcomes in children with all stages of Lyme Disease in partnership with the National Institutes of Health and National Institute of Allergy and Infectious Diseases. She also leads COVID-19 and MIS-C research at Children’s National and is Principal Investigator of a 3-year comprehensive longitudinal study of outcomes in children with COVID-19 and MIS-C in collaboration with the National Institutes of Health. Dr. DeBiasi has authored more than 120 original research, review articles and book chapters. Her research awards include the Infectious Diseases Society of America Young Investigator Award and the John Horsley Prize from the University of Virginia.

“This Chair is particularly meaningful to me because Dr. Parrott was a legendary leader,” says Dr. DeBiasi. “I have read and heard about his legacy at Children’s National for many years. Additionally, he was a virologist, and the focus of my academic career and research has been virology. This wonderful honor will greatly benefit the work of our Infectious Disease Division, and I look forward to working to utilize it to its full potential.”

About the donors

The Robert H. Parrott Professorship in Pediatric Research is supported by many generous donors, including the Charles Engelhard Foundation and the Diane and Norman Bernstein Foundation, Inc.  Through their vision and generosity, these donors are ensuring that Dr. DeBiasi and future holders of this professorship will launch bold, new initiatives to rapidly advance the field of pediatric infectious diseases, elevate our leadership and improve the health of children in the nation’s capital and around the world.

antibodies binding to coronavirus

Biomarker patterns unique to MIS-C and severe COVID in children identified

antibodies binding to coronavirus

Researchers have identified specific biomarker patterns in the blood that are unique to severe COVID-19 infection, as well as others unique to Multisystem Inflammatory Syndrome in Children (MIS-C).

Using powerful sequencing technology, researchers have identified specific biomarker patterns in the blood that are unique to severe COVID-19 infection, as well as others unique to Multisystem Inflammatory Syndrome in Children (MIS-C), a severe complication of COVID-19 infection in children. These findings pave the way for development of potential diagnostic tests in the future, according to a multi-center study published in Cell Reports Medicine. The study includes 416 blood samples from 237 patients at Children’s National Hospital, University of California at San Francisco and Emory University/Children’s Healthcare of Atlanta.

“Our overall goal is to develop tests that can accurately predict if a child with COVID is likely to develop severe disease, and also accurately distinguish children with MIS-C from children with other causes of fever,” says co-author Roberta DeBiasi, M.D., M.S., principal investigator of the study site at Children’s National and chief of the Division of Pediatric Infectious Diseases there. “These two groups of children can decompensate quickly and require rapid diagnosis and more aggressive treatments right from the beginning.”

MIS-C is a condition where different parts of the body, including skin, mucous membranes, gastrointestinal tract, heart, lungs, kidneys or brain can become inflamed after a COVID-19 infection. Researchers still don’t know why some children develop the condition and why minority children are over-represented in MIS-C cases.

The study is funded by National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development as part of a national effort to develop approaches to identify children at high risk of developing MIS-C.

The longitudinal analysis included 416 blood samples from 70 patients with acute COVID-19 (mild, moderate and severe illness) and 141 patients with MIS-C across the three hospitals. Blood samples included those that were collected at the beginning of the illness, during initial recovery, one-month after hospitalization and more than three months after illness.

Investigators used a combination of both whole blood RNA (wbRNA) sequencing, as well as cell-free RNA (cfRNA) and cell-free DNA (cfDNA) sequencing of plasma samples to identify key biosignatures. Information from wbRNA is primarily from circulating white blood cells and identifies inflammatory and immune responses to infection. In contrast, both cfRNA and cfDNA can inform about the levels and types of cell death from peripheral tissues.

“wbRNA analyses revealed that although multiple inflammatory pathways were activated in both severe COVID-19 and MIS-C, there were specific patterns that were unique to each disease and distinguish them from mild COVID and other control conditions,” says Meghan Delaney, D.O., M.P.H., co-author and co-investigator of the study at Children’s National. “This finding can be useful in understanding the pathogenesis of the diseases and also in developing a diagnostic test.”

Additionally, cfRNA and cfDNA analysis from MIS-C patients demonstrated distinct signatures of cell injury and death, including endothelial cells, which are the lining of blood vessels, and a type of neuronal cells called Schwann cells, indicating increased levels of organ injury compared to samples from COVID-19 patients.

“To our knowledge, no one has performed comprehensive analysis of both plasma cell-free RNA and whole blood RNA, as well as cell-free DNA in this setting, which is a powerful approach because it gives us different but complementary types of information,” says Dr. DeBiasi.

During the next three years of the four-year grant, researchers will continue working on developing a test that will accurately distinguish MIS-C from other inflammatory conditions affecting children such as Kawasaki Disease, as well as a test which can predict the likelihood of severe COVID-19 infection. Although this may be applied on a research basis in the near future, Dr. DeBiasi says it can take a period of months to years of regulatory reviews before such a diagnostic test could become available commercially.

Borrelia burgdorferi bacteria

Most children diagnosed with Lyme disease recover fully after treatment

Borrelia burgdorferi bacteria

Lyme disease is caused by the bacterium Borrelia burgdorferi.

Experts found most children diagnosed with Lyme disease recovered within six months of completing antibiotic treatment, according to a new joint study published in Pediatric Research.

The study, which was supported through a partnership between Children’s National Research Institute (CNRI) at Children’s National Hospital and the National Institute of Allergy and Infectious Diseases (NIAID), also revealed that a notably small percentage of children took longer than six months to recover and experienced a significant impact on their daily functioning.

The big picture

This research studied the long-term outcomes of children with Lyme disease through a cross-sectional evaluation using validated surveys. The study collected survey responses from the parents of 102 children ages 5 to 18 years who had been diagnosed with Lyme disease between six months and 10 years before enrollment. Adolescents ages 10 to 18 years were also invited to complete adolescent-specific questionnaires.

According to these parent survey responses, the vast majority (87%) of fully recovered patients did so

within the initial 6-month period after completing antibiotic treatment, with approximately one third recovering within the first month post-treatment and an additional third recovering 1–3 months post-treatment. However, 13% of children who ultimately made a full recovery took longer to do so. At the time of study completion, 6% of children still experienced symptoms attributed to Lyme disease but only 1% experienced symptoms significant enough to impair daily functioning.

Why we’re excited

According to the authors, this study supports previous data showing an excellent overall prognosis for children with Lyme disease, which should help alleviate understandable parental stress associated with lingering non-specific symptoms among infected children.

“These findings can help clinicians manage families’ expectations about the varying post-treatment recovery times of pediatric Lyme disease patients,” says Roberta DeBiasi, M.D., chief of Infectious Diseases at Children’s National Hospital and one of the study’s authors. “It may also give parents relief in knowing that their child has an excellent chance of full recovery after treatment.”

What’s next

Common symptoms of Lyme disease include fever, headache, fatigue and a distinct skin rash called erythema migrans. Without treatment, the infection can spread to joints, the heart and the nervous system.

Antibiotic treatment resulting in full recovery is successful in most Lyme cases. For some, however, symptoms of pain, fatigue or difficulty thinking persist or return after antibiotic treatment. Symptoms that substantially reduce levels of activity and impact quality of life for more than six months after treatment are classified as post-treatment Lyme disease (PTLD) syndrome.

PTLD syndrome remains poorly understood in children and adults, and more research is needed to better understand these prolonged symptoms and identify treatment targets, according to the authors.

You can read the full study, Pediatric Lyme disease: systematic assessment of post-treatment symptoms and quality of life, in Pediatric Research.

pregnant hispanic woman

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

pregnant hispanic woman

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

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

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

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

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

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

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

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

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

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

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

sick child in palliative care hospital bed

New study compares first and second wave of MIS-C

sick child in palliative care hospital bed

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

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

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

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

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

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

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

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

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

coronavirus

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

coronavirus

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

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

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

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

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

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

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

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

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

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

You can find more information about the study here.

little boy at doctor

Demographic, clinical and biomarker features of MIS-C

little boy at doctor

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

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

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

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

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

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

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

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

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

boy in hospital bed

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

boy in hospital bed

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

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

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

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

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

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

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

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

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

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

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.

Acute flaccid myelitis concept illustration

Causes, diagnosis and management of acute flaccid myelitis

Acute flaccid myelitis concept illustration

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.

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

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.

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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

Study finds children can become seriously ill with COVID-19

coronavirus

Despite early reports suggesting COVID-19 does not seriously impact children, a new study shows that children who contract COVID-19 can become very ill.

In contrast to the prevailing view that the novel coronavirus known as COVID-19 does not seriously impact children, a new study finds that children who contract the virus can become very ill—many of them critically so, according to physician researchers at Children’s National Hospital. Their results, published in the Journal of Pediatrics and among the first reports from a U.S. institution caring for children and young adults, shows differences in the characteristics of children who recovered at home, were hospitalized, or who required life support measures. These findings highlight the spectrum of illness in children, and could help doctors and parents better predict which pediatric patients are more likely to become severely ill as a consequence of the virus.

In late 2019, researchers identified a new coronavirus, known as SARS-CoV-2, which causes COVID-19. As the disease spread around the world, the vast majority of reports suggested that elderly patients bear the vast majority of the disease burden and that children are at less risk for either infection or severe disease. However, study leader Roberta DeBiasi, M.D., M.S., chief of the Division of Infectious Diseases at Children’s National, states that she and her colleagues began noticing an influx of children coming to the hospital for evaluation of a range of symptoms starting in mid-March 2020, who were tested and determined to be infected with COVID-19. One quarter of these children required hospitalization or life support.

“It was very apparent to us within the first several weeks of the epidemic that this was a very different situation than our colleagues on the West Coast of the US had described as their experience just weeks before,” DeBiasi says. “Right away, we knew that it was important for us to not only care for these sick children, but to examine the factors causing severe disease, and warn others who provide medical care to children.”

To better understand this phenomenon, she and her colleagues examined the medical records of symptomatic children and young adults who sought treatment at Children’s National for COVID-19 between March 15 and April 30, 2020. Each of these 177 children tested positive using a rapid assay to detect SARS-CoV-2 performed at the hospital. The researchers gathered data on each patient, including demographic details such as age and sex; their symptoms; whether they had any underlying medical conditions; and whether these patients were non-hospitalized, hospitalized, or required critical care.

The results of their analysis show that there was about an even split of male and female patients who tested positive for COVID-19 at Children’s National during this time period. About 25% of these patients required hospitalization. Of those hospitalized, about 75% weren’t considered critically ill and about 25% required life support measures. These included supplemental oxygen delivered by intubation and mechanical ventilation, BiPAP, or high-flow nasal cannula – all treatments that support breathing – as well as other support measures such as dialysis, blood pressure support and medications to treat infection as well as inflammation.

Although patients who were hospitalized spanned the entire age range, more than half of them were either under a year old or more than 15 years old. The children and young adults over 15 years of age, Dr. DeBiasi explains, were more likely to require critical care.

About 39% of all COVID-19 patients had underlying medical conditions, including asthma, which has been highlighted as a risk factor for worse outcomes with this infection. However, DeBiasi says, although underlying conditions were more common as a whole in hospitalized patients – present in about two thirds of hospitalized and 80% of critically ill – asthma didn’t increase the risk of hospitalization or critical illness. On the other hand, children with underlying neurological conditions, such as cerebral palsy, microcephaly, or global developmental delay, as well as those with underlying cardiac, hematologic, or oncologic conditions were significantly more likely to require hospitalization.

In addition, although early reports of COVID-19 suggested that fever and respiratory symptoms are hallmarks of this infection, Dr. DeBiasi and her colleagues found that fewer than half of patients had both concurrently. Those with mild, upper respiratory symptoms, such as runny nose, congestion, and cough were less likely to end up hospitalized than those with more severe respiratory symptoms, such as shortness of breath. The frequency of other symptoms including diarrhea, chest pain and loss of sense of smell or taste was similar among hospitalized and non-hospitalized patients.

Dr. DeBiasi notes that although other East Coast hospitals are anecdotally reporting similar upticks in pediatric COVID-19 patients who become seriously ill, it’s currently unclear what factors might account for differences from the less frequent and milder pediatric illness on the West Coast. Some factors might include a higher East Coast population density, differences between the genetic, racial and ethnic makeup of the two populations, or differences between the viral strains circulating in both regions (an Asian strain on the West Coast, and a European strain on the East Coast).

Regardless, she says, the good news is that the more researchers learn about this viral illness, the better prepared parents, medical personnel and hospitals will be to deal with this ongoing threat.

Other researchers from Children’s National who participated in this study include Xiaoyan Song, Ph.D., M.Sc., Meghan Delaney, D.O., M.P.H., Michael Bell, M.D. , Karen Smith, M.D., Jay Pershad, M.D., Emily Ansusinha, Andrea Hahn, M.D., M.S., Rana Hamdy, M.D., M.P.H., MSCE, Nada Harik, M.D., Benjamin Hanisch, M.D., Barbara Jantausch, M.D., Adeline Koay, MBBS, MS.c., Robin Steinhorn, Kurt Newman, M.D. and David Wessel, M.D.

Dengue virus

Children’s National/NIH team competes in #IDbugbowl

Dengue virus

IDBugBowl team member Maria Susana Rueda-Altez, M.D., hopes her knowledge of infectious diseases common to Peru, like dengue virus, will give her team an advantage.

It’s a bird. It’s a plane. No, it’s an infectious agent that zipped past country borders, infecting international passengers who shared the same commercial aircraft as a person who had symptomatic illness.

The buzzer rings. And the correct answer is: What is severe acute respiratory syndrome?

This fall, a combined team from Children’s National in Washington, D.C. and the National Institutes of Health (NIH) will compete against three other teams testing their collective infectious disease knowledge through IDBugBowl, a Jeopardy-style quiz geared toward fellows, residents and medical students. The competition is held during IDWeek2019. “From anaplasmosis to Zika, any topic is fair game,” according to organizers.

“BugBowl has become so popular that the IDWeek 2019 program committee carved out a separate time for the contest to ensure it would not conflict with any other symposia,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases at Children’s National. “On a day-to-day basis, we all contend with serious infectious diseases that have the potential to jeopardize human health. However, this event helps to expand knowledge among the general public in a fun and engaging way.”

The Children’s National/NIH team participating in the Oct. 5 trivia contest includes:

  • Kevin Lloyd, M.D., third-year pediatrics resident
  • Maria Susana Rueda-Altez, M.D., third-year pediatrics resident
  • Kanal Singh, M.D., fellow, adult infectious diseases at the National Institutes of Health (NIH) and
  • Alexandra Yonts, M.D., fellow, pediatric infectious diseases at Children’s National

Even though she has little formal training in infectious diseases, team member Dr. Rueda-Altez says: “One thing I have in my favor is that I’m from Peru. We’re used to seeing infectious diseases that are less common elsewhere, including tuberculosis and hantavirus.”

And while disease-carrying mosquitoes aren’t abundant at Peru’s higher altitudes, closer to sea level and in its rain forests, infected mosquitoes spread chikungunya, dengue, malaria and Zika, she adds.

Take this quiz to test your infectious disease knowledge.

Dr. DeBiasi

Staying one step ahead of deadly Ebola

Dr. DeBiasi

An ongoing outbreak of Ebola virus since 2018 in the Democratic Republic of the Congo that has resulted in millions of travelers being screened at checkpoints, hundreds of thousands of vaccinations and thousands of deaths is a stark reminder of the need to remain one step ahead of the deadly disease.

To that end, one-half dozen personnel from Children’s National in Washington, D.C., including infectious diseases experts, critical care nurses and laboratory personnel traveled to New York in mid-August for an interactive workshop sponsored by the National Ebola Training and Education Center. They covered how to correctly don and doff protective gear, safely collect, handle and process specimens and discuss the special circumstances that arise when caring for pediatric patients, among other topics.

“Since 2014, Children’s National has evaluated 6 children with exposure as Persons Under Investigation of  Ebola virus disease, 4 of  whom required extended inpatient hospitalization under full isolation precautions,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases. “As a designated Ebola Treatment Center, we must continue our preparedness to care for additional patients with suspected and proven Ebola infection.

“Hands-on training and  drilling offer Children’s National personnel an opportunity to continue to test, evaluate and optimize our institutional Ebola response plan and procedures to maintain our preparedness for the needs of future patients,” adds Dr. DeBiasi.

In addition to Dr. DeBiasi, members of the Children’s National Special Pathogens Isolation Unit team who attended the Emerging Infectious Disease Workshop included:

  • Zohreh Hojjati, Laboratory Medicine.
  • Kristin Elizabeth Mullins, Clinical Lab Director, Laboratory Medicine.
  • Daniel Schroeder, Registered Nurse II, Pediatric Intensive Care Unit (PICU).
  • Melissa Taylor, Registered Nurse II, PICU.
  • Heather Wellman, Registered Nurse II, PICU.

“Among the keys to Children’s National serving as a national exemplar for pediatric Ebola care, is the stability of our multidisciplinary care team and our institutional commitment to ongoing training,” Dr. DeBiasi adds.

During a Grand Rounds presentation at Children’s National in mid-August, Dr. DeBiasi provided updates about recent global infectious disease outbreaks affecting pediatric patients including Ebola, measles, acute flaccid myelitis and Zika Virus. An interdisciplinary panel of Children’s National experts, including nurses, transport specialists, infectious disease and intensive care experts directly involved in caring for Ebola Persons Under Investigation, demonstrated personal protective equipment and fielded questions from staff. The overview also outlined Children’s National institutional expertise and response, including the Congenital Zika Virus Program, the Acute Flaccid Myelitis Task Force, the Special Isolation Unit for Ebola and other highly contagious infectious diseases.

View Ebola preparedness photo gallery.

Sarah Mulkey

MRI and ultrasound imaging detect the spectrum of Zika’s impact

Sarah Mulkey

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D.

Worldwide, thousands of babies have been born to mothers who were infected during pregnancy with Zika, a virus associated with neurological deficits, impaired vision and neurodevelopmental disabilities, among other birth defects. These birth defects are sometimes severe, causing lifelong disability. But they’re also relatively rare compared with the overall rates of infection.

Predicting how many Zika-exposed babies would experience neurological birth defects has been challenging.

However, an international study led by Children’s faculty suggests that ultrasound (US) imaging performed during pregnancy and after childbirth revealed most Zika-related brain abnormalities experienced by infants exposed to the Zika virus during pregnancy, according to a prospective cohort study published online Nov. 26, 2018, in JAMA Pediatrics. Some Zika-exposed infants whose imaging had been normal during pregnancy had mild brain abnormalities detected by US and magnetic resonance imaging (MRI) after they were born.

“A combination of prenatal MRI and US was able to detect Zika-related brain abnormalities during pregnancy, giving families timely information to prepare for the potential complex care needs of these infants,” says Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist at Children’s National Health System and the study’s lead author. “In our study, we detected mild brain abnormalities on postnatal neuroimaging for babies whose imaging was normal during pregnancy. Therefore, it is important for clinicians to continue to monitor brain development for Zika-exposed infants after birth.”

As of Nov. 20 2018, nearly 2,500 pregnant women in the U.S. had laboratory confirmed Zika infection, and about 2,400 of them had given birth, according to the Centers for Disease Control and Prevention (CDC). While more than 100 U.S. infants were born with Zika-associated birth defects, the vast majority of Zika-exposed U.S. infants were apparently normal at birth. The sequential neuroimaging study Dr. Mulkey leads seeks to determine the spectrum of brain findings in infants exposed to Zika in the womb using both US and MRI before and after birth.

The international research team enrolled 82 women in the study from June 15, 2016, through June 27, 2017. All of the women had been exposed to Zika during pregnancy; all but one experienced clinical symptoms by a mean gestational age of 8.2 weeks. Eighty of those women lived in or near Barranquilla, Colombia, and were exposed to Zika there. Two U.S. study participants were exposed to the primarily mosquito-borne illness during travel to Zika hot zones.

All women received fetal MRIs and US during the second and/or third trimester of pregnancy. After their infants were born, the children received brain MRI and cranial US. Blood samples from both mothers and babies were tested for Zika using polymerase chain reaction and serology.

Fetal MRI was able to discern Zika-related brain damage as early as 18 weeks gestation and picked up significant fetal brain abnormalities not fully appreciated in US imaging. In one case, the US remained normal while fetal MRI alone detected brain abnormalities. Three fetuses (4 percent) had severe fetal brain abnormalities consistent with Zika infection, including:

Seventy-five infants were born at term. One pregnancy was terminated at 23 weeks gestation due to the gravity of the fetal brain abnormalities. One fetus with normal imaging died during pregnancy. One newborn who was born with significant fetal brain abnormalities died at age 3 days.

Cranial US and brain MRI was performed on the majority of infants whose prenatal imaging had been normal.  Seven of 53 (13 percent) Zika-exposed infants had mild brain abnormalities detected by MRI after birth. In contrast, postnatal cranial US was better at detecting changes of lenticulostriate vasculopathy, cysts within the brain’s choroid plexus (cells that produce cerebrospinal fluid), germinolytic/subependymal cysts and/or calcifications, which were seen in 21 of 57 (37 percent) infants.

“Sequential neuroimaging revealed that the majority of Zika-exposed fetuses had normal brain development. Tragically, in a small number of pregnancies, Zika-related brain abnormalities were quite severe,” Dr. Mulkey adds. “Our data support the CDC’s recommendation that cranial US be performed after Zika-exposed babies are born. In addition, there is clearly a need to follow these babies over time to gauge whether the brain anomalies we see in imaging affects language, motor and social skills.”

Companion editorial: Revealing the effects of Zika

In addition to Dr. Mulkey, study co-authors include Dorothy I. Bulas, M.D., Gilbert Vezina, M.D., Margarita Arroyave-Wessel, MPH,  Stephanie Russo, B.S, Youssef A. Kousa, D.O, Ph.D., Roberta L. DeBiasi, M.D., MS, Senior Author Adré J. du Plessis, M.B.Ch.B., MPH, all of Children’s National; Christopher Swisher, BS, Georgetown University and Caitlin Cristante, BS, Loyola University, both of  whose contributions included research performed at Children’s National; Yamil Fourzali, M.D., Armando Morales, M.D., both of Sabbag Radiologos; Liliana Encinales, M.D., Allied Research Society; Nelly Pacheco, Bacteriologa, Bio-Nep; Robert S. Lanciotti, Ph.D., Arbovirus Diseases Branch, Centers for Disease Control and Prevention; and Carlos Cure, M.D., BIOMELAB.

Research reported in this news release was supported by the IKARIA fund.

Deer tick

Lyme disease: When will pediatric symptoms resolve?

Deer tick

Over a 13-year period that began in 2004, cases of illness transmitted by ticks, mosquitoes and fleas have more than tripled, the CDC found.

The summer of 2018 was a bad summer for Lyme disease, the tick-borne disease that was first documented in the 1970s in the town of Lyme, Connecticut. While about 30,000 cases of this disease had been reported annually in recent years, studies suggest that the actual number of infections is around 10 times greater.

And according to a study published May 2018 by the Centers for Disease Control and Prevention (CDC), those case numbers may increase over time. Over a 13-year period that began in 2004, cases of illness transmitted by ticks, mosquitoes and fleas have more than tripled, the CDC found.

Lyme disease causes a host of uncomfortable symptoms, ranging from headache and neurological problems, heart problems and eye inflammation in earlier stages, and progressing to joint pain and arthritis in later stages. While it can be treated successfully with appropriate antibiotics, the timeframe for kids’ symptom resolution has been unclear.

A new study by researchers at Children’s National Health System shows that symptoms improve just days or weeks after starting antibiotic therapy for the vast majority of patients, with people whose symptoms had been present a briefer time improving the fastest.

“These findings offer a reassuring timeline for doctors, patients and their families about when patients with Lyme disease can expect to feel better,” says study Senior Author Roberta L. DeBiasi, M.D., MS, Children’s National’s chief of the Division of Pediatric Infectious Diseases and co-director of the Congenital Zika Virus Program. Dr. DeBiasi was recently appointed to serve on a 52-member Tick-Borne Disease Working Group established in 2018 by the Department of Health and Human Services.

Dr. DeBiasi and colleagues collected data retrospectively from the medical records of 78 patients who had been hospitalized at Children’s National for Lyme disease from 2008 to 2015. Each child, who was younger than 18 years old, had documented symptoms and lab tests conclusive for this disease.

Just under one-half had symptoms consistent with early-stage disease, such as:

  • A severe headache
  • Meningitis (inflammation of the membranes covering the brain)
  • Cranial nerve palsy (a nerve dysfunction that affects eye movement and can cause double vision)
  • Multiple erythema migrans rashes (the bulls-eye-shaped rash that’s a hallmark of Lyme disease) and
  • Pseudotumor cerebri (increased pressure inside the skull).

Just over one-half had symptoms consistent with late-stage disease, which mostly consisted of arthritis affecting the knees, along with the hips and elbows in some cases.

In the hospital, each patient was started on an antibiotic that can effectively treat Lyme, including doxycycline, cefotaxime or ceftriaxone, which they continued at home for the prescribed length of the course. The researchers then tracked how quickly the patients’ symptoms resolved.

They report online July 30, 2018, in the Journal of the Pediatric Infectious Diseases Society, that the time to symptom resolution for early stages of disease did not depend on the duration of symptoms prior to starting antibiotics. However, for later stages of disease, patients with longer duration of symptoms prior to starting treatment took longer for their symptoms to resolve.

For patients with early-stage disease, the most common symptom was headache; the median time to symptom resolution was just three days, no matter how long the headache had persisted before treatment started. However, for patients with late-stage Lyme disease, the median time to resolution was 18 days. However, the time depended largely on how long symptoms had persisted before patients began taking antibiotics. For example, patients who had experienced arthritis for less than one week had a shorter time to resolution than those who had arthritis for more than two weeks.

This finding is important, Dr. DeBiasi says, because it suggests that diagnosing Lyme disease earlier – and prescribing the appropriate therapy as soon as possible – can hasten recovery. The vast majority of patients in the study, she adds, eventually experienced full resolution of their symptoms, which should be comforting to families worried about whether their child will ever feel well again.

“We all want what patients and their families want: to feel better as quickly as possible,” Dr. DeBiasi says. “This study gives us valuable information about how soon that will happen given the duration of pediatric patients’ symptoms.”

Dr. DeBiasi and Children’s Psychologist Maureen Monaghan, Ph.D., are leading another Lyme study in collaboration with the National Institutes of Health/National Institute of Allergy and Infectious Diseases to evaluate symptom resolution, quality of life and neurocognitive outcomes in a larger group of pediatric patients with Lyme disease.

In addition to Dr. DeBiasi and Monaghan, Children’s co-authors include Lead Author Mattia E. Chason; Biostatistician Jichuan Wang, Ph.D.; and Yao Cheng.