Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Abstract

Background: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.

Methods: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms.

Results: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).

Conclusions: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Figure 1. Geographic and Temporal Representation of Cases of Multisystem Inflammatory Syndrome in Children (MIS-C).

Panel A shows the cases of MIS-C included in this report according to state; cases are only from the reporting hospitals and do not reflect all cases in each state. Panel B shows statewide pooled percentages of positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) laboratory testing of respiratory specimens from persons younger than 21 years of age as compared with hospitalization dates for patients with MIS-C included from participating hospitals from March 15 to May 15, 2020. The percentage of positivity for SARS-CoV-2 is based on pooled results from tests reported to the Centers for Disease Control and Prevention from commercial and public health laboratories in 25 of the 26 states in which hospitals in our system that reported cases of MIS-C are located.

Figure 2. Organ-System Involvement in Patients with MIS-C.

Cardiovascular involvement and laboratory and diagnostic findings are shown in Panel A, and noncardiovascular complications and diagnostic findings according to age are shown in Panel B. Numbers on each column represent percentages. The denominator for percentages was the 186 patients included in this report, with the exception of the percentages of patients with elevated troponin and B-type natriuretic peptide (BNP), which were calculated among those with reported values (128 patients and 153 patients, respectively). DVT denotes deep-vein thrombosis, ECMO extracorporeal membrane oxygenation, GI gastrointestinal, LAD left anterior descending, and RCA right coronary artery. Panel C is a heat map illustrating the overlap in organ-system involvement among patients with MIS-C. The diagonal represents the percentage of patients with involvement of each organ system. The intersections of rows and columns beneath the diagonal indicate the percentages of patients with both indicated organ systems involved.

Figure 3. Laboratory Markers in Patients with MIS-C Associated with Covid-19.

Denominators varied and are provided in Table S6 in the Supplementary Appendix. Lymphocytopenia was defined as an absolute lymphocyte count of less than 1500 per microliter in patients 8 months of age or older and of less than 4500 per microliter in patients younger than 8 months of age. Neutrophilia was defined as a maximum absolute neutrophil count higher than 7700 per microliter. Increased troponin was defined on the basis of the hospital cutoff for the upper limit of the normal range. No imputations were made for missing laboratory values. ALT denotes alanine aminotransferase, ESR erythrocyte sedimentation rate, FEU fibrinogen equivalent units, and INR international normalized ratio.