• Ashley Grigsby, DO

COVID-19 UPDATE: Multisystem Inflammatory Syndrome in Children (MIS-C)

Once again, we here at pedsinablog felt it was necessary to discuss the recent pediatric concerns regarding COVID-19. Many have heard of the emerging hyper-inflammatory syndrome resembling Kawasaki Disease showing up in pediatric patients of high hit areas of COVID-19. Many have seen this study in the lancet or this recent AAP news release. Here I will attempt to shed some light on what we currently know about this condition: Multisystem Inflammatory Syndrome in Children (MIS-C) with temporal relation to COVID-19. It is important to understand that what we know about this clinical entity is very little and only time will give us a better understanding of the illness; this will focus on what is currently understood as of May 20, 2020.

On May 7, 2020, The Lancet published a case series from mid-April 2020 with a cluster of eight children with hyper-inflammatory shock and symptoms similar to Kawasaki disease (see sidebar), including fever, rash, conjunctivitis, peripheral edema and GI symptoms(1). All of the patients from this case study progressed to fluid refractory shock requiring the use of vasopressors. All of these children had laboratory and clinical evidence of systemic inflammation, including elevated CRP, procalcitonin, ferritin, d-dimer, and/or pericardial effusions, pleural effusions and ascites. No organism was identified as a causative agent for this shock in 7 of the 8 children (one had adenovirus and enterovirus diagnosed). Echocardiogram showed “echo-bright coronary vessels” in these patients and one went on to develop a giant coronary aneurysm as seen in patients with Kawasaki Disease (KD). Three of the children tested positive for COVID-19, including one of the deaths.

Since then, increasing reports of similar cases have been reported. New York has reported, and is investigating, 102 cases of suspected MIS-C, including 3 deaths. Forty percent of these cases have tested positive for COVID-19 antibodies (4). The exact role of COVID-19 remains unclear.

Given this new case entity, the Royal College of Pediatrics and Child Health out of the United Kingdom, has put forth a guidance including a new case definition. This definition is currently the recommend definition by the American Academy of Cardiology as well.


1. A child presenting with persistent fever, inflammation and evidence of single or multi-organ dysfunction (shock, cardiac, respiratory, renal, GI or neurological disorder) with additional features (see appendix here). They may fulfill full or partial criteria for Kawasaki.

2. Exclusion of any other microbial cause

3. COVID-19 PCR testing may be positive or negative

As MIS-C seems to be similar in clinical presentation to KD, below you will find a synopsis of Kawasaki Disease - this definition is separate from MIS-C, but they share many similar clinical features.

Current recommendations regarding treatment of these patients from American College of Cardiology can be found here. I think the take home points from these guidelines are as follows. This entity still remains rare, but a heightened awareness is necessary to appropriately care for these children. Patients with suspected cases of either Kawasaki or atypical Kawasaki, or meeting the case definition for MIS-C, should be sent to a pediatric care center capable of providing a multidisciplinary approach, including cardiology, infectious disease, pediatric critical care, and rheumatology. These patients should undergo serial inflammatory laboratory studies as well as serial echocardiograms. Some of these patients seem to have evidence of elevated inflammation but go on to recover without incident; however, others progress to fluid resistant shock. As such, these patients should be cared for in facilities capable of providing pediatric critical care if it becomes necessary (6).


- Multisystem inflammatory syndrome in children (MIS-C) is a newly emerging clinical entity resembling Kawasaki Disease with associated severe shock and seems to have a temporal relationship with COVID-19

- The exact role of COVID-19 is unclear, and positive PCR or antibody tests are not currently required for this diagnosis

- Patients with suspected MIS-C, Kawasaki, or Atypical Kawasaki should be transferred to pediatric multispecialty facilities capable of caring for critically ill pediatric patients.

- We still know very little about this illness and assumptions about prognosis, clinical course and typical clinical presentations should not be made.


1. Riphagen, S., Gomez, X., Gonzalez-Martinez, C., Wilkinson, N. and Theocharis, P., 2020. Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet,.

2. Jenco, M., 2020. CDC Details COVID-19-Related Inflammatory Syndrome In Children. [online] American Academy of Pediatrics. Available at: <https://www.aappublications.org/news/2020/05/14/covid19inflammatory051420> [Accessed 21 May 2020].

3. Newburger, J., Takahashi, M., Gerber, M., Gewitz, M., Tani, L., Burns, J., Shulman, S., Bolger, A., Ferrieri, P., Baltimore, R., Wilson, W., Baddour, L., Levison, M., Pallasch, T., Falace, D. and Taubert, K., 2004. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. PEDIATRICS, 114(6), pp.1708-1733.

4. Governor Andrew M. Cuomo. 2020. Governor Cuomo Announces State Department Of Health Will Host Statewide Webinar Tomorrow For Healthcare Providers To Discuss Inflammatory Disease In Children Related To COVID-19. [online] Available at: <https://www.governor.ny.gov/news/governor-cuomo-announces-state-department-health-will-host-statewide-webinar-tomorrow> [Accessed 21 May 2020].

5. Royal College of Pediatrics and Child Health. 2020. [online] Available at: <https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf#page4> [Accessed 21 May 2020].

6. American College of Cardiology. 2020. Pediatric Hyperinflammatory Syndrome And COVID-19: Statement And Recommendations From A Pediatric Intensive Care International Collaborative Conference Call - American College Of Cardiology. [online] Available at: <https://www.acc.org/latest-in-cardiology/articles/2020/05/01/01/42/pediatric-hyperinflammatory-syndrome-and-covid-19-statement-and-recommendations-from-a-pediatric-intensive-care-coronavirus-disease-2019-international-collaborative-conference-call> [Accessed 21 May 2020].

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