In a study of 186 pediatric patients with MIS-C in 26 states, cardiovascular involvement leading to vasopressor or vasoactive support was observed most frequently in older children and adolescents. About 5% of children with KD in the United States present with cardiovascular shock leading to support, compared with 50% of the MIS-C patients in this study. 

Cardiovascular Involvement Differences Between MIS-C and Kawasaki’s Disease (KD)


In a study of 186 pediatric patients with MIS-C in 26 states, KD–like features were documented in 74 patients (40%), but 60% of those patients would not have met the complete or incomplete criteria for KD. KD usually affects children under the age of 5. On the other hand, MIS-C has been suggested to affect adolescents and children older than 5 years old. MIS-C also has different cardiovascular involvement compared with KD.

Bowdoin College

Smith College

Many pediatric patients with MIS-C have had fever and mucocutaneous manifestations similar to those of Kawasaki Disease (KD), a rare childhood illness that causes inflammation in the walls of blood vessels and coronary-artery aneurysms. Although the cause of KD remains unknown, an active or preceding infection has been suspected. Some of the KD–like features of MIS-C are also seen in toxic shock syndrome, which has been associated with other viruses.


Relationship Between MIS-C, Kawasaki Disease (KD), and Toxic Shock Syndrome (TSS)

This systematic review of 953 MIS-C cases compiles data regarding epidemiological risk factors of disease and common clinical manifestations. After analyzing the case studies, the authors argued for the WHO case definition of MIS-C as it best represented the longitudinal research. 


Systematic Review of 953 MIS-C Cases 

Feldstein, L. R., Rose, E. B., Horwitz, S. M., Collins, J. P., Newhams, M. M., Son, M. B., ... Randolph, A. G. (2020). Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. New England Journal of Medicine, 383(4), 334-346. doi:10.1056/nejmoa2021680

https://www.nejm.org/doi/full/10.1056/NEJMoa2021680?query=featured_coronavirus

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Comparing Kawasaki Disease (KD) and MIS-C

The comparison groups of children from cohorts with other inflammatory diseases included 
- 1132 patients with KD 
- 45 with KD shock syndrome
- 37 with toxic shock syndrome

Patients with PIMS-TS were generally older than those with KD or KD shock syndrome and had higher white blood cell count, neutrophil count, and CRP, as well as more profound lymphopenia and anemia. They also tended to have lower platelet counts, higher fibrinogen levels, and greater elevation of troponin. Alanine aminotransferase levels and D-dimer levels were similar between those with PIMS-TS and KD and also between those with PIMS-TS and KD shock syndrome. Patients with PIMS-TS tended to be older than those with toxic shock syndrome. Hemoglobin levels were lower, while CRP and alanine aminotransferase levels were higher. Ferritin and troponin results were not available in the toxic shock syndrome group.

Comparison of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 With Other Childhood Inflammatory Diseases 

MIS-C "is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. This rampant inflammation has been recorded in multiple organ systems; yet, clinical research into the pathogenesis of the disease is insufficient. However, we know that many children with MIS-C were exposed or infected with SARS-CoV-2. Currently, the lack of a universal case definition of MIS-C has limited the number of cases that are accurately diagnosed and hampered with proper treatment of the disease. Further research into the clinical, epidemiological and immunological nature of MIS-C is desperately needed. MIS-C can be serious, even deadly, but most children who were diagnosed with this condition have gotten better with medical care."

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19

Severe Covid-19 disease is associated with well-documented comorbidities, like age, cardiovascular and respiratory diseases. However, SARS-CoV-2 infections in children has been described as relatively benign, resulting in minimal hospitalizations and a low mortality rate. Since the beginning of the pandemic, hospitals within Europe and North America have recorded cases of multisystem inflammatory disease in pediatric patients with or previously exposed to Covid-19. Early descriptions have included a wide variety of clinical symptoms, which overlap with other inflammatory conditions like Kawasaki disease and toxic shock syndrome. Nevertheless, MIS-C is a unique condition in which a significant proportion of patients are affected by severe or fatal disease. 

The Origin of MIS-C

Numerous clinical symptoms, encompassing a wide spectrum of organ systems, are associated with MIS-C. The clinical heterogeneity has made diagnoses difficult and misdiagnoses a frequent event. This review has compiled a list of clinical manifestations that a majority of MIS-C patients presented. 
- Fever (922/928; 99.4%)
- Gastrointestinal symptoms (598/699; 85.6%)
- Abdominal pain (315/539; 58.4%)
- Vomiting (306/532; 57.5%)
- Diarrhea (268/532; 50.4%)
- Cardiovascular symptoms (307/387; 79.3%)
- Tachycardia (194/253: 76.7%)
- Hypotension (416/695; 59.9%)
- Myocarditis (128/309; 41.4%)
- Pericardial Effusion (114/511; 22.3%)
- Respiratory Symptoms (295/587; 50.3%)
- Upper respiratory tract symptoms (95/397; 23.9%)
- Dyspnea (101/378; 26.7%)


Clinical Manifestations Recorded by the Review

The isolation of RNA from SARS-CoV-2 was measured through RT-PCR and serological assays that measured the concentration of circulating IgG, IgM and IgA antibodies. Epidemiological protocols, including contact tracing, were also performed. 

SARS-CoV-2 Testing & Diagnostic Criteria

The WHO case definition, which aids clinician in diagnosing MIS-C, comprehensively covered the clinical manifestations of the disease and relationship with SARS-CoV-2. Using the definition to detect MIS-C cases within the records, only 4 mild cases were missed by researchers. However, these 4 cases did not present with multisystem inflammation, a key factor of MIS-C defined by the WHO. 
The case definition from the CDC was only relevant to 62% of cases. 31 cases were missed by the authors due to the lack of multi-organ dysfunction, failing to achieve the CDC diagnostic criteria.


Case Definitions of MIS-C

3/4ths of patients were given intravenous immunoglobulins to support the immune system. Corticosteroids, effective at reducing inflammation, were prescribed in 516 cases out of the 908 studied. Heparin was an anti-thrombotic that was used to reduce the likelihood of thromboses. Treatments that inhibit the innate immune system, specifically cytokine signaling pathways, were prescribed, including: 
- Anakinra (IL-1R inhibitor)
- IL-6 inhibitors (tocilizumab, siltuximab)
- TNFɑ inhibitors (infliximab)
Certain patients had to receive mechanical and non-invasive ventilation due to severe pulmonary inflammation. 


Therapeutic Management of Disease

73.3% of recorded cases were characterized by intensive care treatment, with a median duration of stay of 4 days and a median hospitalization stay of 8 days. 86% of cases experienced severe disease; however, the patients were generally older and suffered from more gastrointestinal and cardiovascular symptoms than a mild course of MIS-C. Laboratory tests done in patients with severe manifestations of MIS-C showed lower WBC counts; increased lymphopenia; higher CRP and ferritin; higher platelet counts, D-dimer and troponin. Of the eighteen deaths reported, 16.7% were patients less than 1 year old, 50% were between the ages of 5-12, and 33.3% were older than 13 years. The majority of patients were male (72.3%) and Black (62.5%). Comorbidities exacerbating fatal cases included obesity, acute leukemia, glucose-6-phosphate dehydrogenase deficiency, asthma and certain neurological conditions. 

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