Treatments and Severe Outcomes for Patients Diagnosed With MIS-C at Four Children's Hospitals in the United States, March 16, 2020-March 10, 2021

Abstract

Background: Clinical management of multisystem inflammatory syndrome in children (MIS-C) has varied over time and by medical institution.

Methods: Data on patients with MIS-C were collected from 4 children's hospitals between March 16, 2020 and March 10, 2021. Relationships between MIS-C treatments and patient demographics, clinical characteristics, and outcomes were described. Propensity score matching was utilized to assess the relative risk of outcomes dependent on early treatment with intravenous immunoglobulin (IVIG) or low-dose steroids, controlling for potential confounding variables.

Results: Of 233 patients diagnosed with MIS-C, the most commonly administered treatments were steroids (88.4%), aspirin (81.1%), IVIG (77.7%) and anticoagulants (71.2%). Compared with those patients without respiratory features, patients with respiratory features were less likely to receive IVIG and steroids on the same day (combination treatment) (44.1%). Controlling for confounding variables, patients receiving IVIG within 1 day of hospitalization were less likely to have hospital length of stay ≥8 days (RR = 0.53, 95% CI: 0.31-0.88). Patients receiving low-dose steroids within 1 day of hospitalization were less likely to develop ventricular dysfunction (RR = 0.45, 95% CI: 0.26-0.77), have increasingly elevated troponin levels (RR = 0.55, 95% CI: 0.40-0.75) or have hospital length of stay ≥8 days (RR = 0.46, 95% CI: 0.29-0.74).

Conclusion: Treatments for MIS-C differed by hospital, patient characteristics and illness severity. When IVIG and low-dose steroids were administered in combination or low-dose steroids were administered alone within 1 day of hospitalization, the risk of subsequent severe outcomes was decreased.

Figure 1.

Percentage of patients receiving treatments for MIS-C by date of admission and clinical characteristics Abbreviations: MIS-C = Multisystem Inflammatory Syndrome in children; IVIG = Intravenous Immunoglobulin; ICU = Intensive Care Unit * Percentage of patients in a demographic category receiving a specified treatment significantly differs from the percentage of patients in other demographic categories receiving the same treatment (p<0.05). For example, patients receiving ICU-level care were compared to all non-ICU patients, regardless of the presence of cardiac complications. Chi square or Fisher’s exact two-sided p-value if any expected cell counts were below 5. ^a Organ system involvement categories are not mutually exclusive ^b The cutoff date of October 22, 2020 for timing of hospitalization reflects the median date of hospital admissions among all patients. ^c Cardiac complications are defined as arrhythmia, pericarditis, myocarditis, mitral regurgitation (mild, moderate, or severe), coronary artery abnormalities (dilatation or aneurysms), elevated troponin, congestive heart failure, ventricular dysfunction (left, right, or dysfunction in both ventricles), or a left ventricular ejection fraction <50%. ^d Mucocutaneous features include the appearance of rash, mucocutaneous lesions, or conjunctival injection. ^e Respiratory features include cough, shortness of breath, chest pain or tightness, pneumonia, acute respiratory distress syndrome (ARDS), or pleural effusion. ^f Cardiac features include shock, elevated brain natriuretic peptide (BNP) or N-terminal pro-hormone BNP (NT-proBNP), elevated troponin. ^g Gastrointestinal features include abdominal pain, vomiting, or diarrhea. ^h Hematologic features include elevated d-dimer, lymphopenia, or thrombocytopenia. Lymphopenia was defined as a lymphocyte count of <4,500 cells per μl for infants aged <8 months, or less than 1,500 cells per ml for persons aged ≥8 months.

Figure 2.

Prevalence of severe outcomes of MIS-C by treatment regimen at day 2 or later of hospitalization^a Abbreviations: ICU = Intensive Care Unit; LOS = Length of Stay; IVIG = Intravenous Immunoglobulin ^a Treatment regimens are not mutually exclusive. Percentages reflect the proportion of patients with severe outcomes within each treatment category. ^b Patients with an outcome of Shock/Hypotension experienced shock, were hypotensive and received vasoactive medications, or received vasoactive medications regardless of shock or hypotension. ^c Patients who were intubated or placed on mechanical ventilation are a subset of patients who received ICU-level care. ^d Any ventricular dysfunction is defined as dysfunction of the left, right, or both ventricles. ^e Any mitral regurgitation is defined as mild, moderate, or severe regurgitation. ^f Coronary artery abnormalities are defined as dilatation or aneurysm indicated by z-score. ^g Immune modulators administered included anakinra, tocilizumab, rituximab, or sirolimus.

Figure 3.

Relative risk of subsequent outcomes for patients with MIS-C receiving IVIG or low-dose steroids within 1 day of hospitalization compared with patients not receiving these treatments within 1 day of hospitalization, using propensity score matching to account for demographic and clinical confounding variables ^a Patients who received ICU-level care stayed in the ICU for one or more days, received treatment with a vasoactive medication, were intubated or placed on mechanical ventilation, or were placed on extracorporeal membrane oxygenation (ECMO). ^b Patients with an outcome of Shock/Hypotension experienced shock, were hypotensive and received vasoactive medications, or received vasoactive medications regardless of shock or hypotension. ^c Coronary artery abnormalities are defined as dilatation or aneurysm indicated by z-score. ^d Ventricular dysfunction is defined as dysfunction of the left, right, or both ventricles. ^e Mitral regurgitation is defined as mild, moderate, or severe regurgitation. ^f Troponin that was elevated (>0.04 ng/ml) and peaked at two or more days following hospitalization ^g Immune modulators administered included anakinra, tocilizumab, rituximab, or sirolimus.

Figure 4.

Relative risk of subsequent outcomes for patients with MIS-C receiving both IVIG and low-dose steroids within 1 day of hospitalization compared with patients only receiving one of these treatments within 1 day of hospitalization, using propensity score matching to account for demographic and clinical confounding variables * Calculation did not converge (risk ratio was not able to be estimated) ^a Patients who received ICU-level care stayed in the ICU for one or more days, received treatment with a vasoactive medication, were intubated or placed on mechanical ventilation, or were placed on extracorporeal membrane oxygenation (ECMO). ^b Patients with an outcome of Shock/Hypotension experienced shock, were hypotensive and received vasoactive medications, or received vasoactive medications regardless of shock or hypotension. ^c Coronary artery abnormalities are defined as dilatation or aneurysm indicated by z-score. ^d Ventricular dysfunction is defined as dysfunction of the left, right, or both ventricles. ^e Mitral regurgitation is defined as mild, moderate, or severe regurgitation. ^f Troponin that was elevated (>0.04 ng/ml) and peaked at two or more days following hospitalization ^g Immune modulators administered included anakinra, tocilizumab, rituximab, or sirolimus.