Multisystem Inflammatory Syndrome in Children

COVID-19, the disease caused by the new coronavirus (SARS-CoV-2), is usually very mild in children. However, as more children have become infected, a new condition has been seen around the world in which children develop an inflammatory response in multiple areas of the body. It is similar to a known condition called Kawasaki disease that we see occasionally, usually in children less than 5 years old. No one knows the cause of Kawasaki disease, but it has long been suspected to be a reaction to a virus of some kind. COVID-19 is so serious in adults because it causes a severe inflammatory reaction in the lungs, so we know that some people tend to respond to this virus with an exaggerated inflammatory reaction. We still don’t know, however, the exact relationship between SARS-CoV-2 infection and MIS-C.

Children with MIS-C have fever, sometimes prolonged, elevated inflammatory markers, and involvement of other systems including the heart, kidneys, skin, lungs, eyes, stomach & intestines. Symptoms may include rashes, abdominal pain, vomiting, diarrhea, pink eye (conjunctivitis), inflammation of the mouth, swollen lymph nodes, sore throat, muscle aches, swollen hands and feet, inflammation of the heart (myocarditis). Many of these are the same symptoms as Kawasaki disease. MIS-C tends to be more severe than Kawasaki disease, and typically affects older children.

In addition to supportive care, it is usually treated with intravenous immune globulin (IVIG), as with Kawasaki disease. Steroids are also sometimes used. If the symptoms are similar to Kawasaki disease, it is also treated with aspirin. At this time, we do not know the optimal treatment, but IVIG does seem to work. It seems to require more treatments though than Kawasaki disease typically does.

Interestingly, heart inflammation (myocarditis) has become a greater concern and now all children who have fever or symptoms 3 or more days due to COVID-19 should have their heart screened after recovery, especially athletes. The main concern, too, with Kawasaki disease is heart damage.

Parents, and pediatricians, need to be aware of and on the lookout for this syndrome. Most children with it will appear ill, and parents will likely seek medical care.

Resources

COVID-19 and Multi-System Inflammatory Syndrome in Children (AAP Healthy Children.org)

Multisystem Inflammatory Syndrome (MIS-C) (CDC)

Multisystem Inflammatory Syndrome in Children (MIS-C) (CHOA)

References

Godfred-Cato S. COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020. MMWR Morb Mortal Wkly Rep. 2020;69. doi:10.15585/mmwr.mm6932e2

Health Advisory Network (HAN-CDC): Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19) May 14, 2020 https://emergency.cdc.gov/han/2020/han00432.asp

AAP Multisystem Inflammatory Syndrome in Children (MIS-C) Interim Guidance

WHO Scientific Brief. Multisystem inflammatory syndrome in children and adolescents with COVID-19.

Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020;383(4):334-346. doi:10.1056/NEJMoa2021680

Whittaker E, Bamford A, Kenny J, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020;324(3):259-269. doi:10.1001/jama.2020.10369

Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020;369:m2094. doi:10.1136/bmj.m2094

Jiang L, Tang K, Levin M, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. Published online August 17, 2020. doi:10.1016/S1473-3099(20)30651-4

Dufort EM, Koumans EH, Chow EJ, et al. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. 2020;383(4):347-358. doi:10.1056/NEJMoa2021756

Miller J, Cantor A, Zachariah P, Ahn D, Martinez M, Margolis KG. Gastrointestinal Symptoms as a Major Presentation Component of a Novel Multisystem Inflammatory Syndrome in Children That Is Related to Coronavirus Disease 2019: A Single Center Experience of 44 Cases. Gastroenterology. Published online June 4, 2020. doi:10.1053/j.gastro.2020.05.079

Abrams JY, Godfred-Cato SE, Oster ME, et al. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2: A Systematic Review. J Pediatr. Published online August 5, 2020. doi:10.1016/j.jpeds.2020.08.003

Bassareo PP, Calcaterra G, Fanos V. Coronavirus disease 2019, Kawasaki disease, and multisystem inflammatory syndrome in children. J Pediatr. 2020;224:184. doi:10.1016/j.jpeds.2020.06.033

Pouletty M, Borocco C, Ouldali N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis. 2020;79(8):999-1006. doi:10.1136/annrheumdis-2020-217960

Sperotto F, Friedman KG, Son MBF, VanderPluym CJ, Newburger JW, Dionne A. Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach. Eur J Pediatr. Published online August 15, 2020. doi:10.1007/s00431-020-03766-6