Mortality and Clinical Characteristics of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 in critically ill patients: an observational multicenter study (MISCO STUDY)

Abstract

Background The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 is widespread and presents a very low mortality rate in highincome countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries compared to described series in high-income countries along with the factors associated with mortality and worse outcomes. Methods An observational cohort study was conducted in 14 PICUs in Colombia between April 01, 2020 and January 31, 2021. Patient´s age ranged between one month and 18 years and they met the requirements set forth by WHO for MIS-C. Results There were seventy-eight children in this study. The median age was seven years (IQR 1- 11), 18% (14/78) were under one year old, and 56% were male. Thirty-five percent (29/78) were obese or overweight. The PICU stay was six days (IQR 4-7), and 100% had a fever on admission lasting five days (IQR 3.7-6). Seventy percent (55/78) had diarrhea, and 87% (68/78) had shock or myocardial dysfunction (78%). Compared to the United Kingdom (UK) study, there were more children under the age of five (37% vs. 10%; p=0.004), and there was a higher frequency of obesity (29.5% vs. 10%; p=0.008). With regard to the US study, there was more lymphadenopathy (23% vs. 13%; p=0.02), diarrhea (70.5% vs. 53%; p=0.001), lymphopenia (64% vs. 35%; p=0.001), shock (87% vs. 35%; p=0.001), elevated troponin (51% vs. 31%; p=0.006) and elevated proBNP (82% vs 43%; p=0.001), as well as greater mortality (9% vs 1.8%; p=0.001). The group that did not survive had a longer duration of the disease until admission to the PICU (6 days vs. 5 days; p = 0.003), more frequency of ferritin above 500 ngr/mL (100% vs. 45%; p = 0.012) and more cardiovascular complications (100% vs. 54%; p = 0.019) compared to the group that survived. Conclusions Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. It was observed inflammatory response, and cardiovascular involvement were conditions that, added to the difficulties in accessing healthcare systems in countries with limited resources, may explain the higher mortality seen in these children.

Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection in KwaZulu-Natal, South Africa

“…7 A younger age for MIS-C was also reported in other low-middle-income countries, including India, Pakistan and Colombia. 10–12 In addition, we found that previously unidentified comorbidities like HIV and malnutrition, although limited by small numbers, may contribute to the higher morbidity and mortality in this setting. 27,28 This study adds to the evidence that significantly elevated biomarkers and critical organ involvement may be associated with severe MIS-C, and it suggests that higher ferritin levels and the need for mechanical ventilation confers a higher mortality risk in this context.…”

“…4–8 However, India, Pakistan, and Colombia have reported MIS-C in younger children (median age 2–7 years) with mortality rates ranging from 9% to 20%. 9–12 There are few studies from Africa; these include a study by Butters et al, 4 a letter by Webb et al 8 from Cape Town, a case series from Sokunbi et al 13 from Nigeria and 2 case reports from Moodley P et al 14 and Onyeaghala et al 15 In the analysis of 469 children hospitalized in 6 sub-Saharan African countries with SARS-CoV-2 infection, 6.1% were noted to have suspected or confirmed MIS-C. 16 While MIS-C was reported in this large multicentre study, the study was limited because of a lack of laboratory and infrastructural capacity to confirm the diagnosis in most countries where the study was performed. Outcomes of children in Sub-Saharan Africa may differ because of the higher burden of childhood diseases like malnutrition, human immunodeficiency virus infection (HIV), tuberculosis (TB) and poorer overall SARS-CoV-2 vaccine coverage.…”

Kawasaki disease and MIS-C share a host immune response

“…The expanded dataset also confirmed that the ViP signatures captured a subset of the genes that are differentially expressed between the MIS-C and Kawasaki disease subgroups, by multisystem inflammation triggered by an antecedent SARS-CoV-2 infection 4 . Of note, MIS-C has a more extreme phenotype than Kawasaki disease, with shock and MAS occurring in approximately 20% and 40% of affected children, respectively, but the incidence of coronary artery abnormalities is similar 5,6 .…”