In adults with COVID-19, it has been observed that independent risk factors associated with mortality included older age, male sex, high fraction of inspired oxygen, high positive end-expiratory pressure, and history of chronic obstructive pulmonary disease, hypercholesterolemia, and type 2 diabetes [9, 10]. Studies that have evaluated which factors could predict severe pediatric COVID-19 have shown that younger age, pre-existing underlying chronic severe comorbidities, male sex and lower respiratory tract infection signs and symptoms at presentation could be considered risk factors for PICU admission [11,12,13]. Among laboratory markers, increased leukocyte count, lymphopenia, and elevated inflammatory markers (C-reactive protein and procalcitonin) were those more frequently associated with PICU admission [11,12,13]. Only in some cases were lactate dehydrogenase, pro-B-type natriuretic peptide and troponin studied and found to be increased, suggesting a potential role of these variables as markers of risk.
Despite these findings, early identification of children who must be carefully monitored for substantial risk of severe COVID-19 remains difficult. Definitive conclusions about the real role of the suggested risk markers as predictors of severity cannot be drawn, as most of the studies have enrolled few patients [6,7,8]. Additionally, the criteria used for enrollment and evaluation differed significantly. The lack of a cutoff level for some parameters does not allow us to establish which patients are truly at risk. Regarding the role of age, there were large differences among studies. In some cases, it was reported that children ≤1 year old were at risk, whereas in others, only children ≤1 month old had a greater probability of developing severe disease [6,7,8]. Most cases of multisystem inflammatory syndrome in children (MIS-C), one of the most severe clinical manifestations of pediatric COVID-19, occur in school-age patients and have marginal epidemiological importance in younger children [14]. The presence of an underlying chronic disease in children admitted to the PICU has been documented in several studies and is generally considered the most reliable marker of severe COVID-19 in pediatrics [6]. However, the prevalence of these factors among PICU patients varies significantly. In some studies, the prevalence of comorbidities was documented in more than 70% of children with severe disease [15]. In a European study, only 52% of PICU cases had an underlying disease [6]. This conflicting evidence suggests that, if an underlying comorbidity may be a risk factor for severe COVID-19 in children, it is not the only factor capable of favoring the worsening of the clinical picture and the development of complications.
More effective identification of at-risk children could be obtained if several variables could be simultaneously considered, and a risk score could be developed. A similar solution was found to be effective in adults by Liang et al. [16] Starting with 72 variables characterizing COVID-19 adult patients, they identified 10 independent predictors of severe or critical disease. With a mathematical model, a well-defined value was attributed to each variable, and a score was developed [16]. Later, it was validated to show high efficacy in predicting a patient’s risk of developing critical illness. However, to prepare a pediatric score, criteria for admission to the PICU must be clarified, including the degree of respiratory impairment and cutoff levels of laboratory tests. The inclusion of potential markers of severity to date have been poorly considered, must be evaluated. 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]. 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. Moreover, increased troponin levels have been repeatedly reported in children with COVID-19 admitted to the PICU [13, 18, 19]. Inclusion of heart enzyme serum levels and evaluation of ventricular function among predictive markers could lead to a more effective evaluation of children at risk with proper selection of those to admit to the PICU and with more adequate treatment in case of more severe clinical manifestations.
