Prognostic Biomarkers for Coronavirus Infection Severity in Preschool Children

Abstract

As for adults, the prognostic predictive factors have been established, including some cytokines, associated with the diagnosis, pathogenesis, and severity of the coronavirus infection (COVID-19). However, predictors for the severity of the course of coronavirus infection in children are not well understood. In addition, there is no information on the cytokine profile in preschool children with COVID-19 as yet. The purpose of the research was to create a predictive model based on a comprehensive analysis of cytokine levels, which would then allow predicting the severity of the course of coronavirus infection in preschool children. Materials and methods used: 21 children (47.6% (10/21) boys and 52.4% (11/21) girls) aged 4.0 [3.0; 4.0] y/o with confirmed coronavirus infection (main group) vs. 25 children (44% (11/25) boys and 56% (14/25) girls) of health group I aged 3.0 [2.9; 3.7] y/o (the control group). Depending on the severity of COVID-19, patients of the main group were divided into subgroups: SG1 of 7 children with asymptomatic COVID-19; SG2 of 7 patients with a mild form; and SG3 of 7 cases of moderate form of the disease. In all children, the presence of SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs was detected by PCR. The concentration of cytokines in blood serum was assessed by the flow fluorometry. Results: in children with COVID-19 at the time of admission to the hospital, the serum concentration of IL-1β, IL-2, IL-4, IL-6, IL-8, IP-10, MCP-1, IFN-γ, and TGF-β1 was statistically significantly higher than in the control group (p<0.05). Thus, based on a comprehensive analysis of the levels of IL-1β, IL-2, IL-6, IL-8, IL-12p70, IP-10, and TGF-β1 at the time of admission to the hospital, the prognostic model was developed allowing predicting the severity of COVID-19 in preschool children (Se=1.0 [95% CI 0.99-1.00], Sp=0.98 [95% CI 0.96-0.99], ROC-AUC=1.0 [95% CI 0.99-1.00], p<0.001; R2=0.93). Conclusion: the results of a comprehensive analysis allow us to consider the indicators of IL-1β, IL-2, IL-6, IL-8, IL-12p70, IP-10, and TGF-β1 as predictors for coronavirus infection severity in preschool children.