Does novel coronavirus infection increase the risk of chronic systemic hyperinflammation and low-grade systemic inflammation in patients with pulmonary tuberculosis?

The development of new coronavirus infectious disease (COVID-19) is associated with an increase in the pro-inflammatory and pro-thrombotic potential of microvascular endothelium. A specific feature of SARS-CoV-2 infection is the post-COVID syndrome that is characterised by long-term impairment of various organs and systems. The immune pathogenesis of post-COVID syndrome in patients with pulmonary tuberculosis requires special attention due to their baseline pro-inflammatory status. The objective of this study was to evaluate the effect of novel coronavirus infection on the risk of chronic systemic hyper-inflammation and low-grade systemic inflammation in patients with pulmonary tuberculosis. Two main groups consisted of patients with pulmonary tuberculosis who had survived COVID-19 (mild form) 3 months ago, or at earlier terms, including the subjects with post-COVID symptoms and those free of these symptoms. The comparison group included patients with pulmonary tuberculosis without a history of COVID-19. The control group was presented by healthy blood donors. Concentrations of IL-6, IL-10, tumor necrosis factor alpha (TNFá), D-dimers, troponin I, cortisol, and endothelin I (ET-I) were measured in patients’ plasma by immunoassay technique. On the basis of these markers, we calculated integral indices of systemic inflammatory response (SIR) – the levels of reactivity (RL), and chronic systemic hyper-inflammation (ChSI). Low-grade systemic inflammation (LGSI) was diagnosed in absence of ChSI, but in cases of simultaneous increase of D-dimer levels 250 ng/ml and ET-I levels 90 pg/ml in the patient. The most prevalent symptoms of post-COVID in patients with pulmonary tuberculosis were tachycardia, arthralgia, and chronic fatigue syndrome, which correspond to the population-wide data. By all empirical parameters, the groups of tuberculosis patients were comparable to each other (p 0.05) and significantly differed from control group. However, evaluation of integral indexes is more crucial for assessing the ‘systemic’ origin of the process. Thus, 23-50% of patients with pulmonary tuberculosis developed subcritical SIR (RL = 1-2), being a feature of ChSI in 7.1-13.6% of cases (both in COVID-19 reconvalescents and non-COVID-19 patients). Meanwhile, all patient groups did not show significant difference in the frequency of LGSI and endothelial dysfunction (p 0.05). However, there was a trend towards an increase of these scores in the following sequence: tuberculosis without COVID-19 – tuberculosis + COVID-19 – tuberculosis + COVID-19 + post-COVID syndrome. Most patients with pulmonary tuberculosis are not characterized by the development of chronic systemic hyperinflammation. LGSI is the most probable feature of general pathology in tuberculosis infection. Tuberculosis infection sufficiently contributes to the development of LGSI, since the frequency and severity of LGSI and its individual manifestations are independent on the new coronavirus infection and signs of post-COVID syndrome.