Secretory IgA and course of COVID-19 in patients receiving a bacteria-based immunostimulant agent in addition to background therapy.

Mucosal immunity plays a major role not only in the prevention but probably also in the outcomes of COVID-19. An enhanced production of secretory immunoglobulin A (sIgA) might contribute to the activation of the immune response mechanisms. To assess the levels of sIgA produced by epithelial cells in the nasal and pharyngeal mucosa and those measured in salivary gland secretions and to study the course of COVID-19 following the combined scheme of intranasal and subcutaneous administration of a bacteria-based immunostimulant agent. This study included 69 patients, aged between 18 and 60, who had moderate COVID-19 infection. They were divided into two groups: Group 1 (control group) included 39 patients who received only background therapy, and Group 2 was made up of 30 patients who received background therapy in combination with the Immunovac VP4 vaccine, a bacteria-based immunostimulant agent, which was given for 11 days starting from the day of admission to hospital. The levels of sIgA were measured by ELISA in epithelial, nasal and pharyngeal swabs, and salivary gland secretions at baseline and on days 14 and 30. The combined scheme of intranasal and subcutaneous administration of the Immunovac VP4 vaccine in the complex therapy of patients with COVID-19 is accompanied by increased synthesis of sIgA in nasal and pharyngeal swabs, more intense decrease in the level of C-reactive protein (CRP) and reduction in the duration of fever and length of hospitalization compared to the control group. Prescribing a immunostimulant agent containing bacterial ligands in complex therapy for COVID-19 patients helps to enhance mucosal immunity and improves the course of the disease.

Use of immunomodulatory therapy as part of comprehensive treatment of non-severe community-acquired pneumonia and its long-term results.

Background: This study investigates the efficiency of two different types of immunomodulators for the treatment of non-severe community-acquired pneumonia (CAP) and assesses their long-term effects. Methods: The study included 55 patients with non-severe CAP. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators simultaneously with the standard therapy: bacterial lysate for group 2 and azoximer bromide (AzB) for group 3. TNF and IL-6 concentrations were determined on the day of hospitalization as well as on days 13 and 60 of follow-up. For 2 years, we monitored the incidence of low respiratory tract infections (LRTIs) in the same patients with CAP (n=55). Results: The overall duration of all symptoms was lower in the immunomodulator groups compared with the control group. During treatment, TNF and IL-6 concentrations decreased on days 13 and 60 in all patients; in patients who received immunomodulators, TNF and IL-6 were reliably lower than in control patients. IL-6 concentration decreased on day 60 in the bacterial lysate and AzB treatment groups and did not differ (p=0.72). The odds ratio for the development of LRTIs in the AzB group was 0.15 (0.02-0.93) (p=0.04), suggesting its protective effect. Conclusion: Inclusion of immunomodulators in the basic treatment of non-severe CAP reduces the duration of symptoms and is associated with improvement of the pro-inflammatory cytokine profile. In 2 years of follow-up, the long-term effects of the immunomodulatory therapy showed a statistically significant lower incidence of LRTIs in the AzB group only. However, given the small sample size of this study, further clinical studies are needed.

Changes in nasal, pharyngeal and salivary secretory IgA levels in patients with COVID-19 and the possibility of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms.

Background: Although extensive research has been conducted on the role of local immunity in patients with SARS-CoV-2, little is known about the production and concentrations of secretory IgA (SIgA) in different mucosal compartments. This article aims to assess the secretion of SIgA in the nasal and pharyngeal compartments and saliva of patients with COVID-19 and to investigate the possibility and efficiency of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms. Methods: This study included 78 inpatients, aged between 18 and 60 years, who had confirmed COVID-19 with moderate lung involvement. The control group (n=45) received basic therapy, and the treatment group (n=33) was additionally administered the bacteria-based pharmaceutical Immunovac VP4 from day 1 to day 10 of hospitalization. SIgA levels were measured by ELISA at baseline and on days 14 and 30. Results: No systemic or local reactions associated with Immunovac VP4 were reported. We observed a statistically significant reduction in the duration of fever and hospitalization in patients who received Immunovac VP4 compared with those from the control group (p=0.03 and p=0.05, respectively). Changes over time in SIgA levels in nasal swabs were found to be significantly different in the two treatment groups (F=7.9, p[78.0]<0.001). On day 14 of observation, patients in the control group showed a statistically significant reduction in SIgA levels from baseline (p=0.02), whereas patients in the Immunovac VP4 group had stable SIgA levels (p=0.07). On day 30 after the start of treatment, there was a statistically significant increase in SIgA levels in the Immunovac VP4 group compared with baseline (from 77.7 (40.5-98.7) µg/L to 113.4 (39.8-156.7) µg/L; p=0.05) and the levels measured on day 14 (from 60.2 (23.3-102.9) µg/L to 113.4 (39.8-156.7) µg/L; p=0.03). The control group showed a statistically significant decrease in levels of nasal SIgA (to 37.3) on day 30 (p=0.007 for comparison with baseline values and p=0.04 for comparison with levels measured on day 14). Changes over time in SIgA levels measured in pharyngeal swabs were also different between the two treatment groups, and this difference reached statistical significance (F=6.5, p[73.0]=0.003). In the control group, this parameter did not change throughout the study (p=0.17 for a comparison between the levels measured on day 14 and the baseline values, and p=0.12 for a comparison between the levels measured on day 30 and the baseline values). In the Immunovac VP4 group, there was a statistically significant increase from baseline in SIgA levels on study day 30: from 1.5 (0.2-16.5) µg/L to 29.8 (3.6-106.8) µg/L (p=0.02). Changes over time in salivary SIgA did not show a significant difference between study groups (F=0.3, p[66.3]=0.75). Conclusion: As part of combination therapy, the bacteria-based immunostimulant agent Immunovac VP4 increases SIgA levels in the nasal and pharyngeal compartments and induces clinical improvement. Induced mucosal immunity is central to the prevention of respiratory infections, particularly in patients with post-COVID-19 syndrome.

Nonspecific Regulation of the Number of Immunocompetent Cells Under the Influence of DT Toxoid in Children With Glomerulonephritis.

Background: Studies aimed at identifying the mechanisms of the immunoregulatory effect of vaccination with diphtheria and tetanus toxoid on the parameters of adaptive immunity in children with kidney pathology are limited. The study aimed to study the effect of revaccination against diphtheria and tetanus on the proliferation and differentiation of immunocompetent cells, the formation of specific antibodies, and the course of the disease in children with glomerulonephritis (GN). Methods: The study included 45 children with glomerulonephritis (GN) aged 5 to 15 years, in remission from 6 months up to 4 years. Of these, 25 children were revaccinated with DT toxoid (Diphtheria-Tetanus toxoid with reduced antigenic content) and 20 were in the control group (not vaccinated). The frequency of development of local and systemic reactions and the course of GN were assessed. The subpopulation structure of lymphocytes was studied in dynamics after 1-6-12 months by flow cytometry and IgG levels to diphtheria and tetanus were studied by ELISA. Results: In 92% of children with GN, the post-vaccination period was uneventful. 8% showed a rise in temperature up to 37.3°C, without the development of local reactions. During the year, none of the patients had an exacerbation of GN or a concomitant disease. After revaccination with DT toxoid, a significant increase in IgG antibodies against diphtheria and tetanus was revealed, which persisted after 12 months - 7.5 [5.1-10.8] IU/mL (p <0.001) and 7.2 [4.8-10.7] IU/mL (p <0.001), respectively. In the post-vaccination period, a multidirectional change in the concentration of T-lymphocytes was noted: with an initially increased level, their percentage after revaccination with DT toxoid decreases from 83 (81-86) % to 78 (76-80)% after a month (p = 0.04) and up to 75 (69-79)% after 12 months (p<0.001). In the control group, such a decrease was not observed. A similar picture was observed for T-helpers, cytotoxic T-lymphocytes, and in patients with an initially low percentage of cytotoxic T-lymphocytes, on the contrary, its increase was noted (p<0.001), which is comparable with the value of this parameter in the group of children with initially normal value (H = 0.54, p = 0.76). The same patterns were observed in the change in the content of B-cells: one month after revaccination, the relative level of B-cells in patients with an initially lowered value increased (p = 0.02) and remained for 12 months (p<0.001). Conclusion: Revaccination with DT toxoid in children with GN not only does not cause undesirable changes in the system of immunocompetent cells but also has an immunomodulatory effect, which contributes to the favorable maintenance of the remission period of the disease.

Comparative Analysis of the Measles Antibody Levels in Healthy Medical Personnel of Maternity Ward and Women in Labor.

It has been proven that post-vaccination immunity to measles virus after two doses of vaccine is not able to persistently protect against infection throughout life. The goal of this research was to determine the immune layer to the measles virus among women in labor and maternity ward personnel in the same medical institution. The levels of IgG antibodies to measles virus in the umbilical cord blood of 594 women in labor and 88 workers of the maternity ward were studied by ELISA. It was revealed that 22.7% of umbilical cord blood serum samples from parturient women and 21.4% of blood serum samples from maternity ward personnel were seronegative (<0.18 IU/ml). Levels of IgG antibodies to measles virus in low values (<1.0 IU/ml) were detected in 67% of blood serum samples among women in labor and 68.9% among employees of the maternity ward. Among women in labor, women under 35 years of age are at the highest risk of contracting measles; the proportion of women with low levels of protective antibodies in this age group was almost 70%, and the proportion of women without protective levels of antibodies was 23%. Compared with the age group 36-43, the age of women in labor under 35 was associated with a higher chance of not having immune protection against infection with measles virus OR [95% CI] = 2.2 [1.1-4.5] (p = 0.02) or had a low level of protection OR [95% CI] = 1.9 [1.2-3.0] (p = 0.001). It was also found that among women over 35 years of age, the proportion of persons with a high level of antibodies in women in labor was statistically significantly higher than among members of the maternity ward staff (13 and 0%, respectively, p = 0.007). Thus, maternity ward employees and women in labor constitute a risk group for measles due to the presence of a high proportion of seronegative persons among women of childbearing age (both maternity ward employees and women in labor). These conditions create the need to revise current approaches to present vaccination procedures, especially in the current epidemiological situation with COVID-19.