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One-half of MIS-C patients at a single center experienced heart complications

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A single center study of patients with multisystem inflammatory disease in children (MIS-C) found that half of children diagnosed with MIS-C had a heart complication as part of the disease. The study collected and analyzed data from 39 cases of MIS-C at Children’s National Hospital in 2020. MIS-C is a pediatric disease that has been linked to SARS-CoV-2, the virus that causes COVID-19.

The study’s findings appear in the journal Cardiology of the Young. The authors aimed to describe the type and frequency of cardiac complications in children with MIS-C while also outlining the disease’s short-term progression. They also hoped to better understand the demographics, clinical and laboratory findings, as well as the therapeutic successes for children with cardiac complications from MIS-C.

“While half of all children at our hospital diagnosed with MIS-C did experience a cardiac complication, it’s important to note that almost all of them (84%) also fully recovered from that cardiac complication within 50 days of diagnosis,” says Ashraf Harahsheh, M.D., director of Quality Outcomes in Cardiology at Children’s National Hospital, who led the study. “We were also able to identify a few common factors among those with cardiac complications that, with further research, may help us identify earlier the children with MIS-C who are at greater risk for heart problems.”

The study found that children with cardiac complications had higher levels of natriuretic peptides, which appear in greater numbers when the heart isn’t pumping enough blood to the rest of the body. Additionally, children who developed heart complications also had higher initial white blood cell counts. MIS-C cardiac complications ranged from mild systolic dysfunction to coronary artery abnormalities and/or artery dilation.

This was a retrospective, observational study of 39 patients admitted to Children’s National Hospital from March 2020 to September 2020 who met the Centers for Disease Control and Prevention MIS-C case definition. Patient demographics, clinical features, laboratory values, diagnostic investigations, including echocardiograms, and therapies were extracted from the electronic medical records.

“This syndrome has some similarities to Kawasaki disease, another inflammatory syndrome that is known to cause cardiac complications,” says Dr. Harahsheh. “Thankfully what we’ve learned from studying and treating Kawasaki disease in children has helped us collaborate with partners around the world to find treatments for MIS-C that seem to minimize the impact of these complications, at least in the short term.”

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

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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

Screenshot of Drs. Northam, Newman and Batshaw

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

Screenshot of Drs. Northam, Newman and Batshaw

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

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

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

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

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

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

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

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

Below are the speakers and the focus of their presentations.

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

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

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

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

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

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Francis Collins

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

Kurt Newman and Francis Collins

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

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

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

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

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

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

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

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

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

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

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

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

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

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An analysis of articles on pediatric COVID-19 cases

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

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

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

Read the full editorial in the Journal of Pediatric Urology.

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

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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)

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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.

mother measuring sick child's temperature

Connections between Kawasaki disease and MIS-C

mother measuring sick child's temperature

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

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

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

Similarities between Kawasaki disease and MIS-C

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

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

Primary differences between Kawasaki disease and MIS-C

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

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

Further study of both Kawasaki and MIS-C needed

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

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

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

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