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.

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis

“…Of these, 2055 duplicate studies were removed; 1663 studies were excluded after title and abstract screening, and 202 were excluded following full text screening based on the set inclusion criteria. Twenty-four studies [ [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] ] were ultimately included in the meta-analysis ( Fig. 1 ).…”

“…Fifteen studies [ 14 , 15 , [20] , [21] , [22] , [23] , [24] , [28] , [29] , [30] , [31] , [32] , [33] , 35 , 37 ] compared MIS-C and COVID-19, and nine of these studies [ 14 , 15 , [22] , [23] , [24] , 30 , 31 , 33 , 37 ] compared MIS-C with severe COVID-19. Eight studies [ [16] , [17] , [18] , [25] , [26] , [27] , 34 , 35 ] compared severe MIS-C with non-severe MIS-C, and three studies [ 17 , 19 , 26 ] compared MIS-C with CAA and MIS-C without CAA. The quality scores of the included studies ranged from 6 to 9, with three studies of moderate quality and 21 studies of high quality.…”

Vaccinating children against SARS-CoV-2

“…Additionally, vaccination may be particularly valuable for some subgroups. Certain chronic conditions, including obesity, predispose children to more severe covid-19,11 and those with markers of inflammation and cardiac distress, such as high levels of C reactive protein, interleukin-6, and brain natriuretic peptide, are more likely to develop serious sequelae such as multisystem inflammatory syndrome 12. Studies to identify whether laboratory markers before infection can predict risk of multisystem inflammatory syndrome should be a research priority, to help target vaccination to vulnerable children.…”

What are the risk factors for admission to the pediatric intensive unit among pediatric patients with COVID-19?

“…Among these is heart involvement [16]. Several findings seem to indicate that, in the first phases of severe COVID-19, signs and symptoms of heart lesions can occur and be useful to select children at risk for complications [13,17,18]. A great number of previously healthy children with MIS-C present with cardiovascular alterations [19][20][21].…”

“…A great number of previously healthy children with MIS-C present with cardiovascular alterations [19][20][21]. Some of them already have signs and symptoms of heart dysfunction in the first phases of disease, and it has been reported that they increase the need for PICU admission, development of potential long-term problems, and risk of death [13,17,18]. Reduced left ventricular systolic function with an ejection fraction < 60%; diastolic dysfunction; and arrhythmias, including ST segment changes, QTc prolongation, and premature atrial or ventricular beat, were the earliest manifestations.…”