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. 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. 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). 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.