When a child arrived at Alfred I. Dupont in April 2020 with symptoms feigning appendicitis, myocarditis, Rheumatic fever, toxic shock syndrome, or possibly, Kawasaki Disease, Dr. Deepika Thacker, medical director of the Cardiac Inpatient Unit at Nemours Alfred I. duPont Children’s Hospital, knew something didn’t quite add up to any of those diagnoses.
Fortunately, that patient was treated and able to go home 12 days later – unbeknownst to the world that said patient was the first in Delaware with a new, rare, serious condition associated with COVID-19. And, it was just the beginning of a new research path for Thacker.
Later in April, a message from the North Central London Clinical Commissioning Group’s Incident Coordination Centre begins to spread, warning physicians across the globe of a COVID-19 related inflammatory syndrome in children or that there may be another unidentified infectious pathogen affecting children.
An international web-based meeting was hosted May 2 via Zoom reporting data of 38 similar pediatric cases between March 25 and April 1. On May 4, the New York City Health Department issued an alert reporting a growing number of pediatric cases between April 17 and May 1. By May 14, the CDC issued a health advisory outlining diagnostic criteria for this emerging syndrome and requiring physicians to report cases. The following day, similar diagnostic criteria was issued from the World Health Organization.
According to the Centers for Disease Control and Prevention, Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, but serious condition associated with COVID-19 in which children present inflammation of the heart, lungs, kidney, brain, skin, eyes, or gastrointestinal organs, as well as fever, abdominal pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, and/or fatigue. The cause of MIS-C is still unknown; however, many children with MIS-C have been infected with COVID-19 or been around someone with COVID-19.
Thacker, who was involved in the initial MIS-C patient case in April, has since been heavily involved in grant-funded research studies to learn more about this new condition affecting children in relation to cardiac symptoms and its similarities to Kawasaki disease, which is marked by fever, rash, red eyes, swollen lymph nodes, irritation in the mouth, lips and throat, and swollen hands and feet.
“It’s very exciting because it has been a while since we’ve had something new to study and there are a lot of diverse ways to study MIS-C – different perspectives,” Thacker said, adding that she hopes the studies will reveal a positive outcome for MIS-C patients years later.
One study is assessing the prevalence of COVID-19-specific antibodies in children presenting with Kawasaki Disease, toxic shock syndrome, and myocarditis between January 1 and May 15, 2020. In addition, this study is assessing the sociodemographic differences between patients within the Kawasaki Disease, toxic shock syndrome, myocarditis, and MIS-C cohort as well as comparing this cohort to a cohort of all children positive for COVID-19 but without cardiac findings. Furthermore, the study is looking at the prevalence of COVID-19 antibodies in a patient’s immediate family.
Thacker said this study “going along very well” and is in the data collection and early data analysis stage. It is on schedule to be completed mid-March 2021. Currently, researchers have funding and processes in place for 40 samples to be bio-banked for future research.
A second study, assessing the long-term outcomes after MIS-C is focusing on coronary artery dilation, coronary artery aneurysms, left ventricular dysfunction, and non-coronary systemic organ dysfunction, inflammation, and major medical events. Currently, six patients have enrolled in this 5-year follow-up study.
Additionally, Thacker is participating in one of eight studies recently funded by the National Institute of Health for the PreVAIL Kids Program, all of which are developing approaches for identifying children at high risk for MIS-C. With fellow researchers, Thacker will be participating in a data science approach to identifying and managing MIS-C associated with SARS-CoV-2 infection and Kawasaki disease in pediatric patients.
In a NIH press release, Director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Diana Bianchi, M.D., said, “These awards underscore NIH’s commitment to identifying children at risk for MIS-C, which will inform development of interventions to improve their health outcomes.”
Unfortunately, there are still many questions about MIS-C, Thacker explained, including: risk factors; progression of the illness; how to better identify it; why it is prevalent in Europe and the eastern United States; the absence of cases in China where COVID-19 originated; increased incidence in certain demographic groups; and, whether pediatric immune responses to COVID-19 vaccines will cause MIS-C.
Multisystem Inflammatory Syndrome in Children (MIS-C) by the Numbers
According to the Centers for Disease Control and Prevention, as of January 8, there are 47 states, New York City, and Washington, D.C., reporting:
- Cases have occurred in children and adolescents from < 1 year old to 20 years old
- Most cases were in children and adolescents between the ages of 1 and 14 years old with an average age of 8 years
- 99% of the total cases have tested positive for COVID-19
- 1% of the total cases were around someone who was infected with COVID-19
- Children developed MIS-C within 2-4 weeks after COVID-19 infection or exposure
- 37% of MIS-C patients have been Hispanic/Latino
- 34% of MIS-C patients have been Non-Hispanic Black