Phagocytic activity of blood monocytes and neutrophils in moderate COVID-19 patients and impact of immune therapy with bacterial lysates

Background Monocytes, macrophages and dendritic cells are involved in phagocytic reactions, which potentially play an important role in the pathogenesis of COVID-19. Imbalance of these cells in peripheral blood has proven to affect not only innate but also adaptive immunity. It is possible that a search for strategies to restore monocyte activity could be a major step in achieving immune control over COVID-19. The aim of this study was to investigate the relationship between phagocytic activity of peripheral-blood monocytes and neutrophils, and COVID-19 severity, to assess the effects of a bacteria-based immunostimulating agent on phagocytosis parameters in in-hospital COVID-19 patients. Materials and methods The study included 105 adult patients with moderate COVID-19, who had been hospitalized in 2020–2021 and treated in accordance with the recommendations of the Ministry of Health of the Russian Federation. All patients were divided into two groups: in Group 1 patients received standard treatment and Immunovac VP4 therapeutic vaccine, a bacteria-based immunostimulating agent as add-on therapy from Day 1 of hospitalization; in Group 2 patients did not receive any add-on treatment. The study parameters included C-reactive protein (CRP), aspartate aminotransferase (AST), SpO 2 , lung involvement on chest computer tomography (CT) scan, and phagocytic activity of peripheral-blood leukocytes based on the absorption activity (AA) of monocytes and neutrophilic granulocytes against S. аureus) . The parameters were assessed at 1, 14 and 30 days. Results Based on a cluster analysis of the clinical findings and the results of diagnostic tests obtained on admission, the patients were divided into 2 clusters: cluster 1 including patients with a more severe disease (n = 34) and cluster 2 including patients with a less severe disease (n = 71). Cluster 1 patients had higher levels of CRP (20.1 vs . 2.2 mg/mL, p < 0.001), AST (32.9 vs . 26.2 U/L, p = 0.003), lower SpO 2 (94% vs . 96%, p < 0,001) and more extensive lung involvement on chest CT scan (35% vs . 12%, p < 0,001). There was a statistically significant direct correlation between blood monocyte AA and SpO 2 (p = 0.04), an inverse correlation between monocyte AA and CRP (p = 0.003) and the extent of lung involvement on CT scan (p = 0.05). In less severe COVID-19 patients (cluster 2), no statistically significant correlation was observed. In more severe COVID-19 patients (cluster 1), there was a rise in monocyte AA on day 30 of hospitalization both in the control group (from 86.6 to 92.2, p = 0.03) and the main group, who received Immunovac VP4 add-on therapy (from 87.3 to 98.3, p = 0.05). However, the patients who received the immunostimulating agent, had higher monocyte PI than the controls, without the immunostimulant (p = 0.05). Patients from cluster 1 who were given Immunovac VP4 had higher SpO 2 levels (98% vs . 97%, p = 0.01) than those who had received only the standard treatment. Discussion Blood monocyte AA correlates with COVID-19 severity: patients with less severe disease have higher AA and those with more severe illness have lower AA. The standard treatment, combined with Immunovac VP4 enhances phagocytic activity of peripheral-blood monocytes, which is associated with a more marked increase in SpO 2 , especially in more severe patients.