Serotonin and 5-hydroxyindoleacetic acid are involved in the pathogenesis of COVID-19 in children

Background. The new coronavirus infection COVID-19 is a pressing health problem around the world. This disease affects the respiratory, cardiovascular and other systems. The role of serotonin as one of the key factors in COVID-19 is discussed in the literature.

Aim. Determination of the concentration of serotonin and its metabolite 5-hydroxyindoleacetic acid in the blood serum of children in the acute period of COVID-19 for use as a diagnostic criterion for the severity of the disease.

Material and methods. A study that included 141 children aged 0 to 17 years was conducted: 92 patients hospitalized in a hospital with a diagnosis of COVID-19 without concomitant pathology made up the study group, 49 healthy children were included in the control group. The subjects were divided into two age groups: younger (0–2 years) and older (3–17 years). The groups of patients and children from the control group were comparable in age and gender. A study of the concentration of serotonin and its metabolite — 5-hydroxyindoleacetic acid — in the blood was carried out using high-performance liquid chromatography, and the results of laboratory and instrumental research methods (obtained from medical records) were evaluated. Based on the results of computed tomography, the proportion of involvement of the lung parenchyma in the pathological process was calculated: CT0 — absence of lung damage; CT1 — less than 25%; CT2 — 25–49%; CT3 — 50–74%; CT4 — more than 75%. Quantitative data were described using median (Me) and lower and upper quartiles (Q1–Q3). To analyze the data, the Pearson χ2 test, nonparametric Kruskal–Wallis and Mann–Whitney tests, as well as the ROC curve method were used. A correlation analysis was carried out using the Spearman coefficient and an assessment of the dependence of a quantitative variable on factors using the linear regression method.

Results. In children with COVID-19 aged 0–2 years, the concentration of serotonin (969.41 pmol/ml) in the blood serum was statistically significantly higher by 49.1 times, in the group of 3–17 years (637.87 pmol/ml) — by 24.5 times compared to age-matched controls (19.74 pmol/ml; p <0.001 and 26.0 pmol/ml; p <0.001, respectively). The concentration of 5-hydroxyindoleacetic acid in patients 0–2 years old (204.90 pmol/ml) was 4.7 times higher relative to healthy children (43.56 pmol/ml; p=0.003), and in the older age group (78.25 pmol/ml) — 2.4 times higher (32.65 pmol/ml; p=0.012), which suggests increased breakdown of serotonin under the influence of monoamine oxidase A. Maximum concentrations of serotonin in blood serum were detected in children aged 0–2 years (1808.79 pmol/ml) with damage to the lung parenchyma from 50 to 74% (grade 3 according to computed tomography). However, in children aged 3–17 years, the maximum concentrations of serotonin (2036.95 pmol/ml) were detected with lung damage ranging from 25 to 49% (grade 2 according to computed tomography). In patients with COVID-19, when the concentration of serotonin in the blood was above 1046.5 pmol/ml, grade 2–4 lung lesions were predicted according to computed tomography, sensitivity 62.5%, specificity 75%.

Conclusion. With COVID-19, a significant increase in the concentration of serotonin and 5-hydroxyindoleacetic acid in the blood was detected in children.