Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

INTRODUCTION: Vidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA. METHODS: Patients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment. The primary endpoint was the need for invasive ventilation after 28 days (ClinicalTrials.gov NCT04379271; EudraCT 2020-001264-28). RESULTS: Between June 12, 2020 and December 10, 2020, a total of 223 were randomized to receive either placebo (n = 112) or vidofludimus calcium (n = 111); three patients withdrew consent and were not treated. Eight (9%) patients in the placebo group and 12 (11%) patients in the vidofludimus calcium group needed invasive ventilation during the 28-day study period, which was lower than the assumed rate of 40%. Time to clinical improvement was shorter by approximately 1 day in the vidofludimus calcium group (15.0 days [90% CI 14.8-15.9]) compared to the placebo group (15.9 days [90% CI 14.9-19.9]). This effect was greatest in patients who initiated therapy within 9 days of symptom onset (3.8 days shorter in the vidofludimus calcium group). Higher trough concentrations of vidofludimus calcium were associated with quicker time to clinical recovery. The rate and timing of appearance of anti-SARS-CoV-2 antibodies were not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo group and 2 (2%) patients in the vidofludimus calcium group; treatment-emergent adverse events of increased severity related to COVID-19 occurred in 13 (12%) patients in the placebo group and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%). CONCLUSIONS: These findings support vidofludimus calcium being safe and well tolerated in patients with COVID-19.

THE VALUE OF SERUM SEROMUCOID IN THE DIFFERENTIAL DIAGNOSIS OF BACTERIAL PNEUMONIA AND TUBERCULOSIS IN HIV-POSITIVE PATIENTS.

OBJECTIVE: The aim: To optimize the differential diagnosis of bacterial pneumonia and tuberculosis in HIV-positive patients based on the value of serum seromucoid. PATIENTS AND METHODS: Materials and methods: The study included 77 HIV-positive patients with lung pathology. The 1st group consisted of 44 HIV-infected patients with BP; the 2nd group - of 33 patients with HIV/TB co-infection. Level of SSM, CD4+ T-lymphocytes, HIV-1 RNA viral load was determined. Сlinical, laboratory, microscopic, radiological, microbiological, and statistical methods were used in the research. RESULTS: Results: In patients with HIV/TB co-infection CD4+ T-lymphocyte level was lower, and viral load was higher than in HIV-infected patients with BP. The level of SSM was statistically significantly elevated in patients of both groups compared with the control (p<0,001), but in patients with HIV/TB co-infection the values were statistically significantly higher (p<0,001). In patients with BP, the content of SSM≤15,95 TU occurred statistically significantly more often than in patients with TB (χ2= 65,5; p <0,001). No statistically significant relationship between SSM content and CD4+ T-lymphocyte levels was found. CONCLUSION: Conclusions: The content of SSM in patients with HIV/TB co-infection is statistically significantly higher than in the group of HIV-infected patients with BP. Determination of SSM level can be used as a rapid method of differential diagnosis of BP and TB in HIV-positive patients that will allow to optimize the diagnostic algorithm at the early stage of hospitalization and to receive the necessary timely treatment for HIV-infected patients.

Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection.

BACKGROUND: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. METHODS: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. RESULTS: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). CONCLUSION: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.