Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study

Abstract

Background: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes.

Methods: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities.

Findings: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]).

Interpretation: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C.

Funding: None.

Figure 1

Study profile MIS-C=multisystem inflammatory syndrome in children. ICU=intensive care unit. *Analysis of clinical variables excluded patients admitted to ICU on the same as day as hospital admission.

Figure 2

Associations between potential explanatory factors and ICU admission Odds ratios were adjusted for sex, age group, race and ethnicity, obesity, and date of MIS-C onset. All potential explanatory factors were binary (yes or no) except for laboratory values, which were continuous (log-transformed and standardised). Elucidation of those odds ratios is shown in figure 4. BNP=brain natriuretic peptide. ICU=intensive care unit. MIS-C=multisystem inflammatory syndrome in children. proBNP=N-terminal pro B-type BNP. *Reference 0–5 years. †Reference Non-Hispanic White. ‡For laboratory values, odds ratios above 1 indicate that higher values increase the odds of the outcome and odds ratios below 1 indicate that lower values increase the odds of the outcome.

Figure 3

Associations between potential explanatory factors and having decreased cardiac function Odds ratios were adjusted for sex, age group, race or ethnicity, obesity, and date of MIS-C onset. All potential explanatory factors were binary (yes or no) except for laboratory values, which were continuous (log-transformed and standardised). Elucidation of those odds ratios is shown in figure 3. BNP=brain natriuretic peptide. proBNP=N-terminal pro b-type BNP. ICU=intensive care unit. MIS-C=multisystem inflammatory syndrome in children. *Reference 0–5 years. †Reference Non-Hispanic White. ‡For laboratory values, odds ratios above 1 indicate that higher values increase the odds of the outcome and odds ratios below 1 indicate that lower values increase the odds of the outcome.

Figure 4

Estimated adjusted odds ratios for outcomes of interest over different values of laboratory markers compared with a reference value Odds ratios were calculated from logistic regression using data from patients not admitted to an ICU on the same day as hospital admission, controlling for sex, age group, race or ethnicity, obesity, and date of MIS-C onset. Solid lines represent odds ratios that significantly differed from the null value of 1, and dashed lines were not statistically significant. Vertical black lines are reference values. BNP=brain natriuretic peptide. ICU=intensive care unit. MIS-C=multisystem inflammatory syndrome in children. proBNP=N-terminal pro B-type BNP.