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).

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The long-term consequences of COVID-19 in those who recover from acute infection requiring hospitalization have not been defined yet. In this study, we aim to describe the long-term symptoms and respiratory outcomes over 12 months in patients hospitalized for severe COVID-19. In this prospective cohort study, patients admitted to hospital for severe COVID-19 were prospectively followed up at 6 and 12 months after discharge from the Hospital of Fermo, Italy. Patients were interviewed for persisting symptoms and underwent physical examination, routine blood test, pulmonary function tests, chest high-resolution CT (HRCT), and 6 min walking test. A total of 64 patients were evaluated and participated in this study. The mean age of participants was 68 years, 41 (64%) were males, and the median body mass index (BMI) was 26 kg/m2. After 6 months, 36% of patients reported persistent dyspnea, 37.5% persistent fatigue, 30.6% hair loss, 14% arthralgia and 11% memory and attention deficits. The rate of these symptoms reduced at the 12 month follow-up. At least 50% of the patients reported anxiety and depression symptoms. At 6 months 57.4% of patients showed reduced DLCO and 21.3% reduced FVC% and improvement at 12 months was noted for FVC but not for DLCO and TLC. Persistent radiographic abnormalities, most commonly ground-glass opacities and interstitial changes, were observed at both timepoints in many patients. Long-term symptoms and pulmonary deficits are common in patients admitted for severe COVID-19. Further studies are needed to assess the clinical significance of long-term consequences of severe COVID-19.

A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.