Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Background: The WHO advised that the impact of COVID-19 pandemic on TB services was estimated to be dramatic due to the disruption of TB services. Methods: A retrospective data collection and evaluation was conducted to include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter). For the purpose of the study, data from patients hospitalized in the same period of 2019 were also collected. Results: In the period of March–August 2019, 201 patients were hospitalized with a diagnosis of TB, while in the same period of 2020, only 115 patients, with a case reduction of 43%. Patients with weight loss, acute respiratory failure, concurrent extrapulmonary TB, and higher Timika radiographic scores were significantly more frequently hospitalized during 2020 vs. 2019. The median patient delay was 75 days (IQR: 40–100) in 2020 compared to 30 days (IQR: 10–60) in 2019 (p < 0.01). Diagnostic delays in 2020 remain significant in the multiple logistic model (AOR = 6.93, 95%CI: 3.9–12.3). Conclusions: Our experience suggests that COVID-19 pandemic had an impact on TB patient care in terms of higher diagnostic delay, reduction in hospitalization, and a greater severity of clinical presentations.

Objectives To identify the best experimental approach to detect a SARS-CoV-2-specific T cell response using a whole-blood platform. Methods Whole-blood from 56 COVID-19 and 23 “NO-COVID-19” individuals were overnight stimulated with different concentrations (0.1 or 1 µg/mL) of SARS-CoV-2 PepTivator® Peptide Pools, including spike (pool S), nucleocapsid (pool N), membrane (pool M), and a MegaPool (MP) of these three peptide pools. ELISA was used to analyse IFN-γ levels. Results IFN-γ-response to every SARS-CoV-2 peptide pool was significantly increased in COVID-19 patients compared with “NO-COVID-19” individuals. Pool S and MegaPool were the most potent immunogenic stimuli (median: 0.51, IQR: 0.14-2.17; and median: 1.18, IQR: 0.27-4.72, respectively) compared to pools N and M (median: 0.22, IQR: 0.032-1.26; and median: 0.22, IQR: 0.01-0.71, respectively). Whole-blood test based on pool S and MegaPool showed a good sensitivity of 77% and a high specificity of 96%. IFN-γ-response was mediated by both CD4 + and CD8 + T cells, and detected independently of clinical parameters in both hospitalized and recovered patients. Conclusions This easy-to-use assay for detecting SARS-CoV-2-specific T cell response may be implemented in clinical laboratories as a powerful diagnostic tool.

Tuberculosis (TB) in the elderly (>65 years old) has increasingly become a global health problem. It has long been recognized that older people are vulnerable to developing tuberculosis. We retrospectively evaluated data from patients older than 65 years diagnosed with pulmonary TB admitted to the National Institute for Infectious Diseases L. Spallanzani, Rome, Italy, from 1 January 2016 to 31 December 2019. One hundred and six consecutive patients were diagnosed with pulmonary TB and 68% reported at least one comorbidity and 44% at least one of the TB risk-factors. Out of the 26 elderly patients who reported an adverse event, having risk factors for TB (O.R. (Odds Ratios) = 1.45; 95% CI 1.12–3.65) and the presence of cavities on Chest X-rays (O.R. = 1.42; 95% CI 1.08–2.73) resulted in being more likely to be associated with adverse events in elderly patients. Having weight loss (O.R. = 1.31; 95% CI 1.08–1.55) and dyspnea (O.R. = 1.23; 95% CI 1.13–1.41) resulted in being significant predictors of unsuccessful treatment outcome in elderly patients. Older people with TB represent a vulnerable group, with high mortality rate, with a challenging diagnosis. Hospitalizations in tertiary referral hospital with clinical expertise in TB management can be useful to improve the outcome of these fragile patients.