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).

This paper reports the authors' preliminary experience with three patients affected by severe acute hypoxemic respiratory failure due to bilateral pneumonia placed in a prone position in Emergency Medicine Ward during application of high flow oxygen nasal cannula. IntroductionIt is well known that, compared with the supine position, placing patients in a prone position determines a beneficial effect of tidal volume distribution, in part by reversing the vertical pleural pressure gradient, which becomes more negative in the dorsal pulmonary regions, thus improving the ventilation/perfusion ratio. Prone position also improves resting lung volumes in dorso-caudal regions by reducing the superimposed pressures of both heart and abdominal organs.1-3 The final result of prone positioning in most subjects with acute hypoxemic respiratory failure due to severe pulmonary consolidation is to exhibit mild to dramatic improvements in oxygenation. Case ReportIn the last three months, three patients were admitted to our Emergency Medicine Ward because they were affected by acute respiratory failure due to pneumonia. Their chest computed tomography (CT) reveals pulmonary infiltrates and ground glass opacities. All patients complained dyspnea, cough and presented arterial blood gases with a PaO 2 /FiO 2 ratio <150. Figures 1 and 2 show the chest X-ray and chest CT scan of one of the three patients.We obtained also an early Intensivist evaluation, which excluded endo-tracheal intubation and admission to Intensive Care Unit.Antibiotics were immediately administrated, saline infusion as needed and patients were submitted to a trial of non-invasive mechanical ventilation. We started with Bi-level Positive Airway Pressure (BiPAP) with a positive end-expiratory pressure (PEEP) of 8 to 12 cm H 2 O, pressure support at 8 to 10 cm H 2 O and FiO 2 at 50%. Every four hours BiPAP was transient interrupted and alternated with two hours of high flow oxygen nasal cannula (HFNC) applied at FiO 2 at 50% with a 60 L/min flow.As reported in Table 1, the most important end points (PaO 2 /FiO 2 ratio and respiratory frequency) did not show any significant improvement in the first 48 hours. For this reason, we placed our patients in a prone position for six hours/day with immediate beneficial effects, both on symptoms and gas exchange. The combination of prone positioning and BiPAP/HFNC improved significantly PaO 2 /FiO 2 ratio with a reduced respiratory frequency within three-four days. Arterial blood gases data (mean values and range) of patients are reported in Table 1.We decided to apply HFNC during prone positioning because it was more confortable than BiPAP for a not-intubated patient.HFNC is a relatively recent method to deliver oxygen in hypoxemic patients. The main advantages of HFNC versus conventional oxygen therapy are: maintenance of warm and humidified gas flow through airways, a good carbon dioxide washout and generation of a slight PEEP. [4][5][6][7] After ten days from admission in our Emergency Medicine Ward, the patient wa...

Tetanus with cephalic involvement is not a typical presentation of the disease; characteristic signs and symptoms are strictly localized in cranial district, although it could frequently progress to the classical generalized form. Tetanus is still spread worldwide, especially in particular subgroups as elderly and newborn babies and in countries with an inadequate vaccine coverage.We report a case of an adult man with generalized tetanus with cephalic presentation in Emergency Department. We aim to outline how difficult it was to diagnose in an adult patient without apparent exposition of previous minimal trauma or injury because of a lot of confusing factors and slow progressing clinical signs. Prompt recognition of signs and symptoms, opportune target therapy and supportive care, in association with correct vaccination schedule, are paramount to determine the prognosis for affected patients.

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Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged.For clarity, all collaborators are listed in this correction article.