Критерії диференційної діагностики туберкульозу легень і негоспітальної пневмонії середньотяжкого та тяжкого перебігу, асоційованої з COVID-19. Частина 2

The coronavirus disease 2019 (COVID-19) pandemic, particularly during its early stages, was characterised by the rapid spread of SARS-CoV-2 infection, which triggered activation of the immune system followed by its subsequent exhaustion. As a result, immune control over Mycobacterium tuberculosis (MTB) was impaired, especially in regions with a high tuberculosis burden and a significant prevalence of latent tuberculosis (TB) infection. These changes may have contributed to a more severe course of tuberculosis and potentially increa­sed the risk of developing resistance to anti-tuberculosis drugs. Objective — to evaluate the relationship between the clinical severity, the cell-mediated immune response, endogenous intoxication, and nitro-oxidative stress in patients with pulmonary tuberculosis, infected with different strains of MTB and concomitant SARS-CoV-2. Materials and methods. A prospective study included 191 newly diagnosed patients with pulmonary TB, distributed into four groups: the 1st study group (1st SG) included 80 patients with drug-susceptible TB, the 2nd study group (2nd SG) comprised 40 patients with primary multidrug-resistant TB (MDR-TB), the 3rd study group (3rd SG) consisted of 49 patients with acquired MDR-TB, and the 4th study group (4th SG) included 22 patients (11 with drug-susceptible TB and 11 with primary MDR-TB) co-infected with SARS-CoV-2. The indices were compared with those of a control group (CG) of 36 conventionally healthy individuals. The laboratory investigations included immunophenotyping of CD3+, CD4+, CD8+, and CD19+ cells, C-reactive protein, ceruloplasmin, circulating immune complexes (CICs), tumour necrosis factor-α (TNF-α), interleu­kin-6 (IL-6) and interleukin-8 (IL-8), leukocyte and hematologic intoxication indices, and erythrocyte sedimentation rate (ESR). Biomarkers of nitro-oxidative stress included nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), advanced glycation end products (AGE), myeloperoxidase (MPO), N-acetyl-β-D-glucosaminidase (NAG) and malondialdehyde (MDA). Results and discussion. Clinical-radiological findings indicated a more severe TB evolution in patients with acquired MDR-TB and those co-infected with SARS-CoV-2, supported by depletion of CD3+, CD4+, CD8+ and CD16+ cells, and strong negative correlations between immune cell levels and disease severity. Elevated CIC-2.5 % and CIC-4.2 %, with increased ESR and acute-phase proteins (C-reactive protein and ceruloplas­min), indicated sustained immune activation and strong associations with disease severity, whereas CIC-8.0 % showed weaker correlations due to rapid systemic clearance. Increased pro-inflammatory cytokines (TNF-α, IL-8, and IL-6) and elevated nitro-oxidative stress markers (NOx, MDA, AOPP, AGEs, NAG, MPO) indicated intensified neutrophil-driven inflammation, systemic inflammatory response, and pronounced lipid, protein, and cellular damage in acquired MDR-TB and concomitant SARS-CoV-2 coinfection. Conclusions. Acquired MDR-TB and SARS-CoV-2 co-infection determine severe clinical-radiological evolution, pronounced cell-mediated immune depletion, sustained immune complex formation and acute-phase activation, intensified cytokine-driven inflammation and nitro-oxidative stress, overall contributing to enhanced immune dysregulation.