Acute respiratory infections (ARI) are the most common disease in the world, and 85.0% of these infections occur in children. The term "recurrent respiratory infections" is used in the modern world scientific literature to define recurrent respiratory diseases. In recent years, the role of a "simple minimal genetic deficiency" in a specific signalling pathway associated with increased susceptibility to respiratory pathogens, as well as nutrient deficiencies, in particular vitamin D, among children with ARI, which are considered as certain phenotypes of this category of children, has been attracting increasing attention among scientists.
Looking through the prism of the current epidemic situation in the world, the question remains whether children with recurrent respiratory infections are at risk of severe COVID-19.
The dissertation is devoted to the study of medical and social risk factors for the development of COVID-19 among children with RRI; features of the clinical course of RRI after coronavirus disease, the relationship between the state of vitamin D supply and the frequency of recurrent episodes of acute respiratory infections, the risk of infection and the development of COVID-19; polymorphic variant rs12979860 of the IFNL gene and I/D of the ACE1 gene in children with RRI and determine their role in the development, infection with SARS-CoV-2 virus and COVID-19 among this category of children. This will allow to identify the risk group among children with RRI and develop differentiated approaches to treatment and prevention measures.
The aim of the study is to improve approaches to treatment and prevention measures in children with RRI during a pandemic by developing a personalised algorithm for their management, taking into account medical and social risk factors, rs12979860 polymorphisms of the IFNL gene and I/D of the ACE1 gene, respiratory system status and vitamin D status.
The dissertation found that among children with COVID-19, 47.2% suffered from RRI, of which 22.3% had a severe course of coronavirus disease with fever (94.7%), general weakness (75.5%), and headache (35.1%).
It has been proven that the development of COVID-19 among children with RRI is facilitated by the following medical and social factors: child's residence in dormitories (OR = 11.25; 95% CI; 1.86 - 68.31; p = 0.001), in families with ≥ 5 people
(OR=0.22; 95% CI: 0.04 - 1.06; p=0.05); attendance children’s clubs (OR=2.47; 95% CI: 1.17 - 5.2; p=0.02), incomplete vaccination status (OR=3; 95% CI, 1.41 - 6.37; p=0.005) and pneumonia at the age of < 3 years (OR=2.28; 95% CI, 1.8 - 5.03; p=0.03).
An inverse correlation was found between the level of vitamin D supply and the frequency of repeated episodes of RI (r= -0.295, p=0.001). In children with insufficient 25(OH)D levels, the risk of SARS-CoV-2 virus infection increased twofold (OR=2.06, 95% CI; 0.740-12.72), while in children with deficiency it increased fourfold (OR 4.72, 95% CI; 1.31-17.03) (≤0.05). Also, an inverse correlation was found between vitamin D levels and the severity of COVID-19 in children with RRI (r = -0.337; p<0.001).
A study was conducted to determine the role of genetic and molecular factors in the course of COVID-19, namely the I/D polymorphisms of the ACE1 gene and rs12979860 of the IFNL gene. The CC genotype is a risk genotype for COVID-19 among children with rhabdomyosarcoma, as well as lung damage.
Genotype II for the I/D polymorphism of the ACE1 gene has been shown to be a risk marker for COVID-19. The I allele is a risk allele for repeated episodes of respiratory infections, including SARS-CoV-2 virus, while the D allele is protective.
Post-COVID changes in the respiratory system were recorded in 67.5% of children with RRI who had COVID-19, characterised by: restrictive pulmonary function disorders (47.5%), bronchial hyperreactivity (10.0%), preservation of inflammatory changes in the airways and a tendency to a decrease in the number of killer (CD56+) and macrophage (CD68+) cells. A direct correlation was found between the number of CD56+ cells (r = 0.61; 95% CI 0.48-0.86; p = 0.001) and serum 25(OH)D concentration.
According to the results of the study was found that in children with a deficiency or insufficient level of serum 25(OH)D and with the CC genotype for the polymorphic variant rs12979860 of the IFNL gene, a dosage of 2000 IU/day was insufficient to prevent RI, including COVID-19, which justifies the need for differential dosage of cholecalciferol in the range of ≥2000 - ≤4000 IU/day.
Based on the studied risk factors, differentiated approaches to treatment and prevention measures for children with RRI were scientifically substantiated and developed, which included, along with general health recommendations (rational nutrition, exercise therapy, breathing exercises), individualised vitamin D supplementation, interferon prophylaxis, and the use of mucosal vaccines.
