Following the coronavirus infection, a variety of symptoms may persist for a long time. Therefore, an important area of further research is to study the state and response of protective immune mechanisms in the post-COVID period. Our aim was to evaluate the dynamics of mucosal immunity by measuring sIgA in the saliva samples and nasal swabs (sIgA, lactoferrin), as well as efficiency of interferon-alpha-2b (IFNa2b) treatment in the patients after coronavirus infection. A study was conducted in the patients aged 18 to 60 years (n = 130) at the terms of 1 to 9 months after a coronavirus infection. A control group consisted of conditionally healthy individuals (n = 15). Diagnosis of post-COVID manifestations was carried out by collecting complaints, anamnestic data, physical examination and questionnaire. The state of mucosal immunity in saliva samples and nasopharyngeal mucosal scrapings was evaluated in dynamics as based on determination of sIgA and lactoferrin concentrations by means of enzyme immunoassay techniques prior to administration of local preventive therapy with recombinant IFNa2b, and 1 month after the treatment (VIFERON gel applied intranasally twice a day for 30 days). The following symptoms of post-COVID syndrome were documented In the study group: joint and muscular pain, shortness of breath, cough, fatigue and weakness, headache and dizziness, anxiety. In the group of patients who received preventive therapy during 1 to 3 months after coronavirus infection, a significantly increased level of saliva sIgA was noted, respectively, 1.840.28 to 5.781.96 mg/mL. As based on the data obtained with scrapings from nasopharyngeal mucosa, a significant increase in the level of sIgA was revealed in the group subjected to therapy up to 3 months after COVID-19 infection, i.e., from 28.613.0 to 39.833.85 mg/mL. In the group of patients devoid of preventive therapy, a stable maintenance of the reduced mucosal immunity parameters was found in all time intervals during the period of convalescence. In all observed patients, regardless of the group, a decreased lactoferrin level was found, being two-fold lower than the normal reference values. The incidence of respiratory viral infections in the group without preventive therapy was statistically significant, being registered in 9.2% of cases. Patients after COVID-19 infection exhibit a persistent decrease in mucosal immunity. Immunological efficacy was observed when using IFNa2b, thus making it possible to recommend it for rehabilitation in this group of patients over the period of convalescence.

Secretory immunoglobulin A, as a marker of the immune response in the mucous membrane, is an available indicator for detecting changes in the local immunity of mucous patients who have undergone COVID-19. Objective. To evaluate the dynamics of changes in the level of sIgA in saliva samples and the effectiveness of the use of interferon α-2b in individuals after a coronavirus infection. Patients and methods. Patients aged 18 to 60 years after COVID-19 infection (group 1 on therapy, n = 65; group 2 without therapy, n = 65) and conditionally healthy individuals (control group, n = 15) were monitored. The material is saliva samples, where the sIgA level was determined initially and after a month. The drug – interferon α-2b, in the form of a gel for topical use (Viferon®, dosage 36,000 IU/g) was administered intranasally 2 times a day, for 1 month. Results. In all groups of patients who underwent COVID-19, the level of saliva sIgA was lower compared to the conditional norm of healthy individuals (6,45 ± 1,81 mg/ml). A month after the administration of interferon α-2b the best effect was observed in patients in the time interval of 1–3 months from the infection, where sIgA was noted a statistically significant increase from 1,84 ± 0,28 to 5,78 ± 1,96 mg/ml. In the groups of patients with later terms, a moderate increase in sIgA was determined (3–6 months: 2,83 ± 0,71 to 3,33 ± 1,78 mg/ml; 6–9 months: 3,53 ± 0,45 to 4,76 ± 2,3 mg/ml) and the absence of infectious diseases during rehabilitation period. In the group without therapy, in all temporal aspects, a persistent decrease in sIgA indicators below normal values was revealed, and the frequency of incidence of respiratory viral infections was noted in 9,2% of cases. Conclusions. During the rehabilitation period, the greatest changes in sIgA in saliva were observed in patients in the first 3 months after the COVID infection. The administration of interferon α-2b to patients in the post-COVID period is accompanied by the normalization of sIgA and prevents the development of respiratory infections. In similar groups, after COVID-19 without therapy, the indicator tends to decrease, and this category of people is at a higher risk of developing other infectious pathologies. Key words: interferon α-2b, COVID-19, mucosal immunity, post-COVID period, secretory immunoglobulin A, saliva

The post-COVID-19 recovery period is characterized by persistence of some symptoms, with immunological alterations being of great importance. Development of preventive measures to normalize mucosal immunity after a coronavirus infection determines the relevance of the current study. The aim. To study dynamics of clinical symptoms and level of secretory immunoglobulin A in individuals after a novel coronavirus infection as well as evaluate effectiveness of using interferon alpha-2b. Materials and methods. A study was conducted with patients aged 18 to 60 years old (n=130), surveyed 1 to 9 months after post-infection, as well as in apparently healthy individuals lacking COVID-19 (n=15). Previous novel coronavirus infection and post-COVID manifestations were verified based on medical documentation, complaints, anamnesis data, physical examination and questionnaires. The concentration of salivatory and nasopharyngeal mucosal sIgA was measured dynamically prior to and after administration of local therapy with interferon alpha-2b (gel applied intranasally twice a day for 30 days). Results. The acute period of COVID-19 was characterized by fever, anosmia, fatigue and weakness, muscle and joint pain. Among the post-COVID manifestations at early period (1-3 months), pain in the joints and muscles (75,0%) as well as elevated body temperature (21,2%) were reliably detected, whereas in the long period (6-9 months) there were revealed dominance with the same frequency of shortness of breath, muscle and joint pain (75,8%, respectively). Based on examination data in healthy subjects, there was determined an arbitrary normal range of secretory IgA in saliva 6.451.81 mg/ml and nasal swabs 13.433.24 mg/ml. In the group of patients 1-3 months post-infection, therapy with interferon alfa-2b one month later resulted in significantly increased level of secretory IgA in saliva (from 1.840.28 to 5.781.96 mg/ml) and in nasal swabs (from 28.613.0 to 39.833.85 mg/ml) by more than 3- and 1.5-fold, respectively. In the group of patients without therapy was featured with stably sustained decline in sIgA level up to 9 months after COVID-19. In particular, the level of saliva sIgA ranged from 2.360.56 down to 2.160.66 mg/ml, and in nasal smears from 15.661.32 to 10.231.07 mg/ml that differed insignificantly compared to baseline level. The rate of respiratory diseases prevailed in this group (27.6% of cases), which fully lacked in the group of topically administered interferon alpha-2b. Conclusion. In the post-COVID period, multiple organ disorders persist and reduced sIgA level is registered. Intranasally applied interferon alfa-2b made possible to normalize sIgA level and prevent accumulation of respiratory infectious pathologies.

Immune defense mechanisms in survivors of the COronaVIrus Disease-19 (COVID-19) and development of their rehabilitation during the pandemic both portray a great scientific and practical interest.The aim of the study was to explore effect of Immunovac-VP-4® (I-VP-4), a vaccine based on bacterial ligands, on the clinical and airway mucosal immunity parameters, along with systemic immune response in a group of medical workers in post-COVID period and in persons who did not develop the disease.Methods. 82 healthcare workers aged from 18 to 65 years were included in a prospective open controlled study. The participants were divided into 4 groups: groups 1 (n = 20) and 2 (n = 27) included those with a history of COVID-19, and groups 3 (n = 18) and 4 (n = 17) included those who did not have the disease. Volunteers in groups 1 and 3 received I-VP-4. Samples of oral fluid, induced sputum, nasopharyngeal and oropharyngeal mucosa scrapings, and venous blood were examined. The levels of total secretory immunoglobulin class A (sIgA) and immunoglobulin G (IgG) were determined by enzyme immunoassay. The phagocytic index (PI) of leukocytes was assessed by flow cytometry.Results. The group of patients who did not have COVID-19 and received IVP-4 (Group 3) showed a tendency to a smaller number of COVID-19 cases, as well as some reduction in days of incapacity for work due to the acute respiratory infections (ARI). The vaccine improved airway mucosal immunity parameters and innate immune response. sIgA increased in the induced sputum (p < 0.005) and unchanged in the oropharyngeal mucosa samples in Group 1. The PI of macrophages in oral fluid doubled (p < 0.05) in this group. At the same time, those parameters decreased in Group 2. In non-infected vaccinated patients (Group 3), a significant increase of PI of blood monocytes was found on the day 90 of the study (p < 0.05). Also, a four-fold increase of PI of macrophages in oral fluid in comparison with Group 4 (p < 0.05) was noted.Conclusion. I-VP-4 improved airway mucosal immunity mechanisms and the systemic immune response. The vaccine can be recommended for rehabilitation programs for COVID-19 survivors and for prevention of ARIs.

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