Cellular immunity plays an important role in the control of SARS-CoV-2. Lymphopenia and a decrease in the functional activity of cells may be among the main reasons for deterioration of clinical outcomes of the disease. Usage of the bacterial therapeutic vaccine Immunovac-VP-4 during the inflammation phase may be promising for immunomodulation of the cellular immunity. The aim of our study was to evaluate the dynamics of lymphocyte subpopulations in hospitalized patients with COVID-19 upon combining the basic therapy with immunotropic drug based on the antigens from opportunistic pathogens. The study included 45 patients (18-70 years old) admitted with a confirmed diagnosis of moderate/severe infection caused by the COVID-19 virus. In addition to basic therapy, 33 persons of this group received Immunovac-VP-4 by a combined nasal-oral method. Subpopulation activity of peripheral blood lymphocytes in patients over time (at baseline, on the 14th and 30th day after hospitalization) was studied by flow cytometry by means of FC-500 Cytomics (Beckman Coulter, USA) using monoclonal antibodies (mAb) (Immunotech, France). In the group receiving only standard therapy, an increased number of T lymphocytes was detected on day 14 (79.9 (75.5-81.6), p = 0.00252), on day 30 from the start of treatment (78.4 (74.25-79. 2), p = 0.03662), and a decrease in B lymphocytes on day 14 (10.6 (7.78-11.63), p = 0.03236), on day 30 (7.85 (6.25-11.1), p = 0.01352) relative to baseline parameters upon admission. We revealed more pronounced changes in the parameters of cellular immunity relative to the initial parameters, i.e., an increased proportion of T lymphocytes on the 14th day (80.1 (73.8-84.2), p = 0.00018), and 30th day from starting the treatment (80.2 (76-81.9)), T helpers at 14 days after treatment (50.2 (43-57), p = 0.00694), cytotoxic T cells by 30th day of therapy (26.35 (24-29.4), p = 0.0114), decrease in B lymphocytes on day 14 (13.1 (8.2-16.9), p = 0 00158), on the 30th day from the start of treatment (8.2 (7.6-9.7), p <0.00001), and a transient decrease in NK cells on the 14th day (3.7 (2,1-6.3), p = 0.00308), with their recovery on the 30th day of observation to 8.6 (6-12.5) in the Immunovac-VP-4 group. Modulation of cellular immunity may be important for the virus clearance.