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Background: Angiotensin-converting enzyme 2 (ACE2) is not only the entry route of SARS-CoV-2 infection but also triggers a major mechanism of COVID-19 aggravation by promoting a hyperinflammatory state, leading to lung injury, hematological and immunological dysregulation. The impact of ACE2 inhibitors on the course of COVID-19 is still unclear. The effect of ACE2 inhibitors on the course of acute respiratory distress syndrome (ARDS) during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF) was investigated. Methods: A cohort study of critically ill patients with COVID-19 and other respiratory diseases (widespread infection, pneumonia) who underwent treatment in The Critical Care Unit of the First University Clinic (Tbilisi, Georgia) during the 2020-2021 years was conducted. The impact of the ACE2 inhibitors on the course of the ARDS developed during COVID-19 and other severe respiratory infections in conditions of different severity of HF was evaluated. Results: In COVID-19-infected (I) and uninfected (II) patients with ARDS, ACE2 inhibitors reduce the levels of Ang II, C reactive protein (CRP) and D-dimer (I: from 1508.07 ± 26.68 to 48.51 ± 24.35, from 233.92 ± 13.02 to 198.12 ± 11.88, from 7.88 ± 0.47 to 6.28 ± 0.43; II: from 1000.14 ± 149.49 to 46.23 ± 88.21, 226.48 ± 13.81 to 183.52 ± 17.32, from 6.39 ± 0.58 to 5.48 ± 0.69) at moderate HF and Ang II, CRP levels (I: from 1845.89 ± 89.37 to 49.64 ± 51.05, from 209.28 ± 14.41 to 175.37 ± 9.84; II: from 1753.29 ± 65.95 to 49.76 ± 55.74, 287.10 ± 20.50 to 214.71 ± 17.32) at severe HF, reduce interleukin-6 (IL-6) expression at moderate HF (I: from 1977.23 ± 354.66 to 899.36 ± 323.76) and cause reduction of pCO2 index at severe HF (I: from 69.80 ± 3.22 to 60.44 ± 2.20) in COVID-19-infected patients. Conclusion: Study results show that the ACE2 inhibitors play an important role in the regulation of inflammatory processes in both COVID-19-infected and uninfected patients with ARDS. ACE2 inhibitors decrease immunological disorders, inflammation, and lung alveoli dysfunction, especially in COVID-19-infected patients.
RESUMO
INTRODUCTION: Adherence to second-line antituberculosis drug is challenging. A combination of strategies needs to be implemented to achieve adherence. In Georgia an optimized adherence support (OAS) - a package of education, psychosocial support and adherence counselling - was added to the already existing package of adherence support (supervised treatment, adherence incentives, transport cost reimbursement) to improve adherence and increase treatment success. We assessed the additive benefits of OAS on adherence and treatment outcomes. METHODOLOGY: This was a before and after cohort study using routine programme data in the National Center for Tuberculosis and Lung Diseases in Tbilisi. All adult rifampicin- and multidrug-resistant tuberculosis (RR/MDR-TB) patients enrolled for treatment under directly observed therapy in the NCTLD during the period before (June 2015 - January 2016) and after (June 2017 - January 2018) were included in the study. Primary outcomes were: i) adequate adherence defined as ≥ 85% of days covered by TB medication during the whole treatment period; ii) final treatment outcomes. RESULTS: Of 221 RR/MDR-TB, most patients were male (76%, N = 167) with a mean age of 41 ± 14 years. Adherence data was available for 111 patients in the 'before' and 97 patients in the 'after' cohort. Adequate adherence was achieved by 62% (69/111) in the 'before' and 70% (68/97) in the 'after' cohort (p = 0.290). Overall treatment success was 64% (73/114) and 63% (67/107) in the 'before' and 'after' cohorts respectively (p = 0.937). CONCLUSIONS: Implementation of OAS had modest effect on adherence and had no additive benefits on treatment outcomes among RR/MDR-TB patients on 18-20 months regimen.