Table 3.
Comparison between multisystem inflammatory syndrome in children (MIS-C), Kawasaki disease (KD), toxic shock syndrome (TSS) and severe COVID-19 disease in children and adults
| Characteristics | MIS-C | KD | TSS | Severe COVID-19 in children without MIS-C | Severe COVID-19 in adults |
|---|---|---|---|---|---|
| Age of presentation | Usually in children aged 8–10 years | Usually in children below 5 years (slightly older in KDSS) | Usually in children above 10 years | Usually in adolescents | Fatality rates higher in advanced age |
| Gender difference | Male > female | Male > female | Male < female | Male = female | Male > female |
| Affected ethnicity | Hispanic/Latino/African American > White | East Asian | No ethnic variation known | No difference | No difference |
| Fever | Present | Present | Present | Present | Present |
| Cutaneous signs | Similar to KD but full range of spectrum seen in < 50% | Typical signs seen in majority of patients | Usually erythroderma and petechiae | Usually absent; rarely, chilblain like lesions on toes (COVID toes) have been reported in adolescents | Acro‐ischemia in fingers and toes, cyanosis, cutaneous bullae, dry gangrene and maculopapular rash |
| Lymphadenopathy | Not common | More common | Less common | Not known | Less common |
| Hemodynamic instability and ICU support | Hemodynamic instability present in almost all patients | Less than 5% of patients have KDSS | Usually present | Seen in patients with multiorgan dysfunction | 5–12% of all cases |
| Cardiovascular Complications | Cardiac dysfunction is seen at presentation; severe myocarditis and pericarditis are more common; CAAs are usually restricted to mild dilatation and small-sized aneurysms | Symptomatic myocarditis is not common; both coronary artery dilatation and aneurysms are seen | Myocardial dysfunction, CAAs and valvular regurgitation are usually not seen | Myocardial dysfunction, CAAs and valvular regurgitation are usually not seen | Myocardial dysfunction, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events are reported |
| Predominant manifestations | Gastrointestinal manifestations (abdominal pain, diarrhea) are prominent and present in > 80% patients; some present with acute surgical abdomen | Gastrointestinal symptoms are usually not prominent | Rash, hypotension | Cough, respiratory distress may be present; gastrointestinal symptoms are less common | Cough, respiratory distress is common |
| Inflammatory markers | Markedly increased levels of inflammatory markers compared to classical KD; lymphopenia common; cytokine storm is more severe; extremely high levels of NT-pro-BNP, Troponins and d-dimers | Neutrophilic leukocytosis is usual | Neutrophilic leukocytosis is usual | Lymphopenia and neutropenia may be seen in 1/3rd patients; however, increased lymphocyte counts may also be seen | Inflammatory markers are raised; lymphopenia is common |
| Organ dysfunction | Multiorgan dysfunction seen | Multiorgan dysfunction is not common | Renal and CNS involvement is common | ARDS; MAS, shock are common | ARDS, heart failure, renal failure, liver damage, shock, and multiorgan failure are common |
| Underlying etiology | Putative post-infectious syndrome; SARS-CoV-2 serology is usually positive; in seronegative patients there is usually history of contact with an individual having COVID-19 infection | No identifiable cause | Focus of staphylococcal or streptococcal infection often present | Underlying comorbidity may be present; SARS-CoV-2 RT-PCR usually positive | Underlying comorbidity usually leads to severe disease; SARS-CoV-2 RT-PCR usually positive |
| Anti-HCoV antibodies | 70–90% | Paucity of data | No data | Nearly 90% of infected children develop antibodies | Seen in almost all patients after 2 weeks of infection [101]a |
| Autoantibodies | Few reports | Less common | No data | No data | Noted in only one studyb [102] |
| T cells | Lymphopenia | Involvement of cytotoxic T cells | Lymphopenia | Usually unaltered | Lymphopenia in severe disease |
| Co-morbidities as risk factors | Possibly underlying immunodeficiency states | Not common; rarely seen with primary immunodeficiency and occasionally seen in context of acquired immunodeficiency | Usually not significant | Co-morbidities (e.g., malignancy, chronic lung diseases, and neurological disorders) are associated with severe forms of disease | Co-morbidities (e.g., hypertension, diabetes mellitus, chronic heart or lung disease) are associated with severe forms of disease |
| Management | IVIg; steroids; IL-1 blockers; IL-6 inhibitors | IVIg; steroid; IL-1 blockers | Antibiotics, IVIg | Antiviral agents, antibiotics, IVIg, steroids, IL-6 inhibitors | HCQS, IL-6 inhibitors; steroids; convalescent plasma; antiviral therapies |
ARDS acute respiratory distress syndrome, CAA coronary artery aneurysm, CNS central nervous system; ICU intensive care units; KDSS Kawasaki disease shock syndrome, MAS macrophage activation syndrome, TSS toxic shock syndrome, IVIg intravenous immunoglobulin, HCQ hydroxychloroquine
References: [19, 68], aLong et al. Nat Med. 2020 Jun;26(6):845–848, bGazzaruso C et al. Clin Rheumatol. 2020;39(7):2095‐2097