MICRONUTRIENT STATUS (VITAMINS A AND D) AND ITS EFFECT ON THE SEVERITY OF THE COURSE OF COVID-19 IN CHILDREN

H. Pavlyshyn, O. Labivka, K. Kozak
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Abstract

A strong immune response is important during recovery from COVID-19, and its status is infl uenced by several micronutrients. Vitamin D is important in regulating the immune response and protecting against respiratory infections. Vitamin A also has immunomodulatory eff ects, inhibiting viral replication and enhancing immune responses, thereby reducing morbidity and mortality from COVID-19. The aim of research was to study the levels of vitamins A, D, and retinol- binding protein 4 in children with COVID-19, and their associations with the severity of the disease.Material and Methods. 112 children aged 1 month to 18 years with COVID-19 confi rmed by polymerase chain reaction (PCR)in nasal swabs or by a positive serologic test (IgM and IgG or IgM). In all children, vitamin D levels were determined by thecolorimetric enzyme- linked immunosorbent assay (ELISA) using the Monobind test system. Vitamin A and retinol binding protein 4 (RBP4) levels were determined by the colorimetric enzyme- linked immunosorbent assay (ELISA) using the Elabscience test system. Statistical analysis was performed using Stat Plus (its 95 % confi dence interval (95 % CI) was calculated for the mean values, and the Kruskal- Wallis test (H-test) was used as the reliability criterion for checking the equality of the medians of several samples). The level of statistical signifi cance was set at P<0.05). The study was conducted in accordance with the rules of patient safety and ethical principles of scientifi c medical research involving human subjects (2000). The permission to conduct this study was granted by the Bioethics Commission (Protocol No. 73, dated April 3, 2023). The parents (legal representatives) of the patients gave their written consent to the conduct of this study. This study is a fragment of research work «Optimizing the diagnosis of clinical and pathogenetic characteristics of the COVID-19 coronavirus infection in children with comorbid pathology and treatment features» (state registration No. 0123U100064, 2023-2025).Results. The mean age of the children was (7.04±5.75) years (95 % CI 5.96-8.12). According to the severity of the disease,57 children (50.89 %) had a mild course, 43 children (38.39 %) had a moderate course, and 12 children (10.72 %) had a severe course. The concentration of vitamin D in children with mild course of COVID-19 was 30.91 ng/ml, in children with moderate course – 29.10 ng/ml, in children with severe course – 22.42 ng/ml (Р<0.05). The level of vitamin A also varied in children with diff erent severity of the disease: in mild COVID-19 it was 456.10 ng/ml, in moderate – 347.30 ng/ml, and in severe – 242.90 ng/ ml (Р <0.001). At the same time, the level of retinol binding protein 4 was 30.66 ng/ml in mild disease, 33.07 ng/ml in moderate disease and 23.28 ng/ml in severe disease.Conclusions. Children with moderate and severe COVID-19 have signifi cantly lower levels of vitamins A, D, and RBP4compared to uninfected individuals. Vitamin A and RBP4 levels were age-dependent, and vitamin D levels did not show agerelated patterns. Lower levels of vitamins A and D are associated with higher levels of pro-infl ammatory markers – CRP,leukocytes and ESR.
微量营养素状况(维生素 A 和 D)及其对儿童科维-19 病程严重程度的影响
在 COVID-19 的康复过程中,强有力的免疫反应非常重要,而其状态受到多种微量营养素的影响。维生素 D 对调节免疫反应和防止呼吸道感染非常重要。维生素 A 也具有免疫调节作用,可抑制病毒复制,增强免疫反应,从而降低 COVID-19 的发病率和死亡率。本研究旨在研究 COVID-19 儿童体内维生素 A、D 和视黄醇结合蛋白 4 的水平及其与疾病严重程度的关系。112 名 1 个月至 18 岁的 COVID-19 患儿通过鼻拭子聚合酶链反应(PCR)或阳性血清学检测(IgM 和 IgG 或 IgM)进行了确诊。所有儿童的维生素 D 水平都是通过使用 Monobind 检测系统的比色酶联免疫吸附试验 (ELISA) 测定的。维生素 A 和视黄醇结合蛋白 4 (RBP4) 含量通过使用 Elabscience 测试系统的比色酶联免疫吸附试验 (ELISA) 进行测定。使用 Stat Plus 进行统计分析(计算平均值的 95 % 置信区间(95 % CI),并使用 Kruskal Wallis 检验(H 检验)作为检验多个样本中位数是否相等的可靠性标准)。统计意义水平设定为 P<0.05)。本研究的开展符合患者安全规则和涉及人类受试者的医学科学研究伦理原则(2000 年)。生物伦理委员会批准了本研究的进行(2023 年 4 月 3 日第 73 号协议)。患者的父母(法定代理人)以书面形式同意开展本研究。本研究是 "优化COVID-19冠状病毒感染儿童的临床和病理特征诊断及治疗特点"(国家注册号:0123U100064,2023-2025)研究工作的一个片段。患儿的平均年龄为(7.04±5.75)岁(95 % CI 5.96-8.12)。根据病情严重程度,57 名患儿(50.89%)为轻度病程,43 名患儿(38.39%)为中度病程,12 名患儿(10.72%)为重度病程。COVID-19轻度病程儿童的维生素D浓度为30.91纳克/毫升,中度病程儿童的维生素D浓度为29.10纳克/毫升,重度病程儿童的维生素D浓度为22.42纳克/毫升(Р<0.05)。病情严重程度不同的儿童的维生素 A 含量也不同:轻度 COVID-19 的维生素 A 含量为 456.10 纳克/毫升,中度为 347.30 纳克/毫升,重度为 242.90 纳克/毫升(Р<0.001)。同时,视黄醇结合蛋白 4 的水平在轻度疾病中为 30.66 纳克/毫升,中度疾病中为 33.07 纳克/毫升,重度疾病中为 23.28 纳克/毫升。与未感染者相比,中度和重度 COVID-19 儿童的维生素 A、D 和 RBP4 水平明显较低。维生素 A 和 RBP4 水平与年龄有关,而维生素 D 水平与年龄无关。维生素 A 和维生素 D 水平较低与促炎症指标(CRP、白细胞和血沉)水平较高有关。
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