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News & Articles > Pediatric COVID-19: MIS-C

Dr. Sarah Bauer, MD, Assistant Professor, Department of Pediatrics, Medical College of Wisconsin

Update to Chapter 291 “Coronaviruses,” Nelson Textbook of Pediatrics, 2-Volume Set, 20th Edition (Elsevier, 2019). 


On May 14th, 2020 the Centers for Disease Control and Prevention (CDC) posted a health advisory regarding the rare and newly discovered pediatric disease associated with COVID-19, the multisystem inflammatory syndrome in children (MIS-C).1 Presentation is similar to other inflammatory diseases in children, such as Kawasaki disease, toxic shock syndromes, and sepsis.2 MIS-C has been described as Kawasaki-like and hyperinflammatory shock. The CDC case definition is:

-An individual aged <21 years presenting with fever (≥38ºC or subjective fever for ≥24 hours), laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological)

-No alternative plausible diagnoses

-Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms

Case Reports, Complications, and Treatment

Italy reported cases of inflammatory disease in children related to COVID-19 starting in February, with the United Kingdom noticing cases in mid-April.3,4 In the Bergamo province of Italy, one hospital noted a 30-fold monthly increase in Kawasaki-like disease since the start of the COVID-19 pandemic. The 10 patients in the post-COVID-19 group were more likely to be older (7.5 vs 3 years), have a higher BMI, have higher CRP, neutrophil, and ferritin levels, have lower white blood cell, lymphocyte, and platelet counts, and abnormal ECHO’s as compared to the 19 patients in the previous 5 years.3 Eighty percent of the post COVID-10 group were positive for COVID-19 IgG, IgM, or both, however only 2 were positive for COVID-19 PCR, suggesting post-infectious inflammation. Symptoms of macrophage activation syndrome were more common in this group as well. All patients received IVIG and 8 received adjunctive treatment with steroids with a 100% response to treatment.3 The authors estimate based on the limited data acquired from the region that the incidence of this Kawasaki-like illness is rare, no more than one in 1000 exposed children.

A pediatric ICU in London, UK reported 8 pediatric cases of hyperinflammatory shock in a 10-day period in April. Children were previously healthy, 6 were of Afro-Caribbean descent, and all but one were above the 75th percentile for weight.4 Labs included elevated CRP, procalcitonin, ferritin, triglycerides and D-dimers. Troponin were elevated in 5 patients and all patients had an elevated proBNP. Most ECHOs were abnormal but non-specific. All tested positive for COVID-19 antibodies, all were treated with IVIG and antibiotics, 6 received aspirin, all received isotropic support, one patient received infliximab, and one patient developed an arrhythmia, progressed to shock, and died of a cerebrovascular infarct.

On May 19th, 2020 Cohen Children’s Medical Center (CCMC) in Queens, NY reported on 33 patients with MIS-C in a 1-month period during a CDC webinar. The average age was 8.6 years with a male predominance; the majority of patients were previously healthy (79%) and 39% were obese.5 On presentation fever had lasted approximately 4 days. Other symptoms included neurocognitive issues (58%), gastrointestinal symptoms (97%), respiratory symptoms (52%), shock (76%), and Kawasaki criteria (64%). Laboratory findings were similar to previous studies and included mild anemia, lymphopenia, hypoalbuminemia, and elevated CRP, procalcitonin, D-dimer, fibrinogen, ferritin, troponins, and proBNP’s. Seventy-three percent were positive for COVID-19 IgG and negative PCR. One hundred percent of patients received IVIG, 70% received methylprednisolone, and 88% received aspirin. Immunomodulators (anakinra, tocilizumab, and infliximab) were used less frequently, with Anakinra being the most popular and used in 12% of patients. Acute kidney injury occurred in 70%, 18% required mechanical ventilation, no deaths had occurred, and 83% were discharged alive at the time of the webinar.

Cardiac complications, such as myocarditis, pericardial effusion, and coronary artery dilation have been described in children. CCMC reported myocardial dysfunction in 58% of their patients.5 France and Switzerland noted heart failure in 35 patients with suspected MIS-C in a 2 month period from 14 ICUs, a third of which had a left ventricular ejection fraction of <30% and no deaths occurred.6

In adult ICU patients, increased fibrinogen and D-dimer suggest a hypercoagulable state secondary to inflammatory cytokines rather than DIC; patients may require antithrombotic therapy and at minimum prophylactic dosing.7 This inflammatory state has led to both pulmonary embolisms as well as microthrombi and an increased risk of death in adults,8 yet data is lacking in children.

Guidelines and Recommendations

The Royal College of Paediatrics and Child Health published a guideline on MIS-C to raise awareness, describe the syndrome, and give management advice.2 In all children, persistent fever of >38.5ºC  is present and most have hypotension and require oxygen; other complaints include abdominal pain, conjunctivitis, cough, lymphadenopathy, mucus membrane changes, rash, cough, sore throat, and gastrointestinal symptoms. Chest XR can show patchy infiltrates and pleural effusions. Per their guideline, all patients have the following abnormal labs:2

  • Abnormal Fibrinogen
  • High CRP
  • High D-dimer
  • High Ferritin
  • Hypoalbuminemia
  • Lymphopenia

Close monitoring of end organ dysfunction with hourly vital signs for at least the first 12 hours of admission and frequent labs is recommended; an ICU setting may be necessary, along with a multidisciplinary approach including infectious disease experts, cardiologists, and rheumatologists.2 While MIS-C patients tend to be older and have more cardiac complications than children with Kawasaki disease, treatment is similar given both processes appear to be post-infectious. Kawasaki disease treatment is well studied and involves IVIG, aspirin, and the use of corticosteroids and/or immunomodulators such as infliximab, etanercept, or anakinra for refractory disease and anticoagulation for patients with coronary artery aneurysms.9-11 Similarly, thus far, treatment for MIS-C includes supportive care, IVIG, aspirin, consideration of steroids or other immune modulators (anakinra, tocilizumab, and infliximab have all been used) in refractory inflammation, and enoxaparin for prophylaxis or treatment if thrombosis is diagnosed.4,5 Other recommended therapies are antibiotics until cultures are negative, inotropes for shock, and investigation of antiviral trials that may be applicable pending the child’s condition.2,5

As of May 21, 2020 New York City Department of Health and Mental Hygiene has reported 89 confirmed MIS-C cases.13 The CDC health advisory encourages health care providers to report suspected cases to their local or state health departments in order to collect more data and better define this new pediatric syndrome.


1.         Centers for Disease Control and Prevention. Emergency Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Published 2020. Accessed May 27, 2020.

2.         Royal College of Paediatrics and Child Health Guidance. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. Published 2020. Accessed May 29, 2020.

3.         Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020.

4.         Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395(10237):1607-1608.

5.         Centers for Disease Control and Prevention. Emergency Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19) Webinar. In:2020:

6.         Belhadjer Z, Méot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020.

7.         Panigada M, Bottino N, Tagliabue P, et al. Hypercoagulability of COVID-19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis. J Thromb Haemost. 2020.

8.         Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020;7(6):e438-e440.

9.         Portman MA, Dahdah NS, Slee A, et al. Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial. Pediatrics. 2019;143(6).

10.       Pilania RK, Jindal AK, Guleria S, Singh   S. An Update on Treatment of Kawasaki Disease. Vasculitis. 2019;5:36-55.

11.       Dionne A, Dahdah N, Singh-Grewal D, Burgner DP, Newburger JW, de Ferranti SD. Anti-thrombosis management of patients with Kawasaki disease: Results from an international survey. Int J Cardiol. 2020;307:154-158.

12.       National Institutes of Health. Care of Critically Ill Patients with COVID-19. Published 2020. Updated May 12, 2020. Accessed June 1, 2020.

13.       NYC Health. New York City Reports at Least 89 Cases of Multisystem Inflammatory Syndrome in Children (MIS-C). Published 2020. Accessed May 29, 2020.

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