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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ObjectivesP-wave duration (PWD) is associated with the development of atrial arrhythmias, cardiovascular and all-cause mortality. With this study, we aimed to assess the distribution and determinants of PWD in the general population.DesignCross-sectional study using data collected between 2014 and 2016.SettingIn the population-based cohort CoLaus|PsyCoLaus, Lausanne, Switzerland, we used 12-lead ECGs to measure PWD. Potential demographic, clinical and biological determinants of PWD were collected by questionnaire, anthropometry, blood pressure measurement and biological assays.ParticipantsData from 3459 participants (55% women, 62±10 years, 93% Caucasian) were included. Participants were excluded if they presented with (1) no sinus rhythm or paced rhythm on the study ECG or Wolff-Parkinson-White ECG pattern; (2) missing or non-interpretable ECG; and (3) missing phenotypic data.Primary outcome measureDetermine (1) the PWD distribution and (2) the demographic, clinical and biological determinants of PWD in a large population-based cohort.ResultsMedian and IQR of PWD was 112 (102–120) ms . In the multivariable analyses, PWD was significantly associated with age (p<0.001) and height (p<0.001), with an adjusted regression coefficient (95% CI) of 0.29 ms/years (0.23 to 0.36) and 0.32 ms/cm (0.28 to 0.37), respectively. PWD, given thereafter in ms with adjusted mean±SE, was significantly (p<0.05) associated with (a) gender (woman 110.0±0.4; man 112.1±0.4), (b) body mass index (normal 110.1±0.4; overweight 110.9±0.4; obese 113.0±0.5), (c) abdominal obesity (no 110.5±0.3; yes 111.7±0.4) and (d) hypertension (no 110.4±0.3; yes 111.7±0.4).ConclusionPWD is positively associated with age, height, male gender, obesity markers and hypertension. Clinical interpretation of PWD should take these factors into consideration.