THE EFFECT OF COVID-19 INFECTION ON THE COURSE OF CHRONIC INFLAMMATORY DISEASES OF THE UPPER RESPIRATORY TRACT AND THE STATE OF IMMUNITY

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INFLUENCE OF MUCOSAL VACCINATION ON INDICATORS OF LABORATORY RESEARCH IN PATIENTS WITH CHRONIC INFLAMMATORY DISEASES OF THE UPPER RESPIRATORY TRACT VACCINATED AGAINST COVID-19

Melnikov OF, Zabolotnyі DI, Volosevych LI, Tymchenko MD, Sambur MB, Sidorenko TV, Faraon IV, Rylska OG, Smagina TV, Tupitska OD, Peleshenko NO, Zayets TA

State Institution “O.S. Kolomiychenko Institute of Otolaryngology of National Academy of Medical Sciences of Ukraine”
Email: amtc@kndio.kiev.ua

Abstract

Introduction: The use of immunotropic drugs in infectious and inflammatory diseases is a promising area of practical medicine. Clinical studies have established that the appointment of patients with chronic inflammatory diseases of the upper respiratory tract (URT), vaccinated against COVID-19, a mucosal vaccine of bacterial origin (OM-85), led to an improvement in the course of their main otolaryngological disease and decrease in the number of acute respiratory viral infections. The improvement of the general clinical condition of such patients after mucosal vaccination raised the question of which mechanisms were responsible for this.

The purpose of the study: to determine the effect of mucosal vaccination on indicators of systemic and local immunity and the microbiota of oropharyngeal secretions in patients with chronic inflammatory diseases of the upper respiratory tract, vaccinated against COVID-19.

Materials and methods: The study included patients with chronic inflammatory diseases of the upper respiratory tract. They were divided into three research groups: 1^st – patients with chronic inflammatory diseases of URT who were not sick and were not vaccinated against COVID-19 (n=7); 2^nd – patients with chronic inflammatory disease who were vaccinated against COVID-19 (n=12); 3^rd – patients with chronic inflammatory diseases of URT who were sick with COVID-19 and were vaccinated against this viral disease (n=15). All of them were prescribed a lyophilized lysate of bacteria that often cause infectious diseases of the upper respiratory tract (OM-85). The drug was prescribed in accordance with the manufacturer’s recommendations. 4^th (control) group consisted of donors (n=32), represented by clinically healthy individuals who were examined before the COVID-19 epidemic.

Laboratory study of indicators of systemic and local immunity and assessment of microbiological parameters of oropharyngeal secretions in patients with chronic inflammatory diseases of URT were carried out twice – before the appointment and 6 months after they took OM-85. Cytotoxic activity of natural blood cells of peripheral blood was evaluated by the level of destruction of metabolically inactive nucleated erythrocytes of chickens by the spectrophotometric method (Stat Fax-2100, USA). The percentage of CD¹⁶⁺ cells among blood lymphocytes (Lf) was determined using monoclonal antibodies. The content of circulating immune complexes (CIC) in blood and saliva was assessed by the method of precipitation with a PEG-6000 solution. The concentration of γ-interferon (γ-IFN) in blood sera and secretory immunoglobulin A (sIgA) in oropharyngeal secretions was determined using sets of reagents for enzyme-linked immunosorbent assay (Euroimmune) on the Stat Fax-2100 reader (USA).

The qualitative composition of the microflora cultured from the oropharyngeal secretions of patients with chronic inflammatory diseases of URT was identified by morphological, tinctorial, cultural and biochemical properties according to standard methods. The level of insemination of the oropharyngeal secretion with bacteria was assessed by two parameters: a) the content of microorganisms isolated from 1.0 ml of mixed saliva, which was determined as the cumulative decimal logarithm of the number of colony-forming units (CFU) – ∑lg CFU/ml and b) the percentage of pathogenic and conditionally pathogenic (transient) microflora (TMF) from the total content of microorganisms isolated from oropharyngeal secretions.

The reliability of the differences of the obtained results was assessed using the one-sided non-parametric Mann-Whitney “U” test and Fisher’s exact method (EFT). Data are given in the form of median values (Me) and quartiles (Q25-Q75).

Results and discussion: It is possible to ascertain the absence of a reliable effect of mucosal vaccination on such indicators of systemic cellular immunity as the total number and functional activity of natural blood cells in the blood of patients with chronic inflammatory diseases of URT. The decrease in the content of circulating immune complexes in the blood of patients with chronic inflammatory diseases of URT 6 months after taking OM-85 looked like a vector and was within the normal range. It was shown that the concentration of interferon gamma was reduced compared to both donors and baseline data. Studies of the state of local immunity established that the content of sIgA in the oropharyngeal secretions of patients of the first and second groups after taking OM-85 was variable and did not go beyond the norm, but in general there was a positive vector towards the increase of this immunoglobulin. After taking the drug OM-85, the content of immune complexes in the secretion of the oropharynx increased, but reliably – only in those vaccinated against COVID-19.

The most significant data are the results of a decrease in the level of gamma-interferon in the blood after taking a mucosal vaccine. It can be assumed that this result could be evidence that the appointment of OM-85 drug to patients with chronic inflammatory diseases of URT, regardless of their vaccination against COVID-19, over time reduced their need for γ-IFN as a protective factor against viral infections, as well as regulatory factor.

The direction of changes in indicators of systemic and local immunity in patients with chronic inflammatory diseases of the upper respiratory tract caused by taking an immunotropic agent of bacterial origin on the background of the vaccination against COVID-19 indicates that mucosal vaccination does not contribute to the normalization of the content and functional activity of natural killer cells in patients, the presence of γ-interferon and circulating immune complexes in the blood, although it causes the tension of the local defence mechanisms of the mucous membrane, which can affect the improvement of their general clinical condition.

Conclusions: Mucosal vaccination in patients with chronic inflammatory diseases of URT contributes to a significant decrease in the content of transient microflora and an increase in the number of immune complexes in the oropharyngeal secretions of patients vaccinated against COVID-19 and who have suffered this disease. Protective mechanisms of local immunity are more active in the implementation of OM-85 reception.

Key words: chronic inflammatory diseases of the upper respiratory tract, COVID-19, systemic and local immunity, OM-85 vaccine, microflora of upper respiratory tract.