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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Background: Pneumomediastinum, subcutaneous emphysema and pneumothorax are not rarely observed during the COVID-19 pandemic. Such complications can worsen gas exchange and the overall prognosis in critical patients. The aim of this study is to investigate what predisposing factors are related to pneumomediastinum and pneumothorax in SARS-CoV2-Acute Respiratory Distress Syndrome (ARDS), what symptoms may predict a severe and potentially fatal complication and what therapeutical approach may provide a better outcome. Methods: In this single center cohort study, we recorded data from 45 critically ill COVID-19 patients who developed one or more complicating events among pneumomediastinum, subcutaneous emphysema and pneumothorax. All patients showed ARDS and underwent non-invasive ventilation (NIV) at baseline. Patients with mild to moderate ARDS and pneumomediastinum/pneumothorax (n = 25) received High Flow Nasal Cannula (HFNC), while patients with severe ARDS and pneumomediastinum/pneumothorax underwent HFNC (n = 10) or invasive mechanical ventilation (IMV) (n = 10). Results: Pneumomediastinum/pneumothorax developed in 10.5% of subjects affected by SARS-coV2-ARDS. Dyspnea affected 40% and cough affected 37% of subjects. High resolution computed tomography of the chest showed bilateral diffuse ground glass opacities (GGO) in 100% of subjects. Traction bronchiolectasis, reticulation, crazy paving and distortion were observed in 64%. Furthermore, 36% showed subcutaneous emphysema. Non-severe ARDS cases received HFNC, and 76% patients recovered from pneumomediastinum/pneumothorax over a median follow up of 5 days. Among severe ARDS cases the recovery rate of pneumomediastinum/pneumothorax was 70% with the HFNC approach, and 10% with IMV. Conclusion: HFNC is a safe and effective ventilatory approach for critical COVID-19 and has a positive role in associated complications such as pneumomediastinum and pneumothorax.

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AimsTo estimate if chronic anticoagulant (CAC) treatment is associated with morbidity and mortality outcomes of patients hospitalized for SARS-CoV-2 infection.MethodsIn this European multicentric cohort study, we included 1186 patients of whom 144 were on CAC (12.1%) with positive coronavirus disease 2019 testing between 1 February and 30 July 2020. The average treatment effect (ATE) analysis with a propensity score-matching (PSM) algorithm was used to estimate the impact of CAC on the primary outcomes defined as in-hospital death, major and minor bleeding events, cardiovascular complications (CCI), and acute kidney injury (AKI). We also investigated if different dosages of in-hospital heparin were associated with in-hospital survival.ResultsIn unadjusted populations, primary outcomes were significantly higher among CAC patients compared with non-CAC patients: all-cause death (35% vs. 18% P < 0.001), major and minor bleeding (14% vs. 8% P = 0.026; 25% vs. 17% P = 0.014), CCI (27% vs. 14% P < 0.001), and AKI (42% vs. 19% P < 0.001). In ATE analysis with PSM, there was no significant association between CAC and primary outcomes except for an increased incidence of AKI (ATE +10.2%, 95% confidence interval 0.3–20.1%, P = 0.044). Conversely, in-hospital heparin, regardless of dose, was associated with a significantly higher survival compared with no anticoagulation.ConclusionsThe use of CAC was not associated with the primary outcomes except for the increase in AKI. However, in the adjusted survival analysis, any dose of in-hospital anticoagulation was associated with significantly higher survival compared with no anticoagulation.

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Introduction In COVID-19 associated hypoxemic acute respiratory failure (ARF) without mandatory indication for urgent endotracheal intubation, a trial of CPAP may be considered. We aimed to evaluate HACOR (heart rate, acidosis, consciousness, oxygenation, respiratory rate) score performance in these patients as predictor of CPAP failure. Methods Prospective observational multicentric study (three centers in different countries), including adult patients with SARS-CoV-2 pneumonia admitted to a respiratory intermediate care unit, presenting PaO 2 /FiO 2 < 300 and PaCO 2 < 45 mmHg, who received CPAP. One hour after starting CPAP, HACOR was calculated. Results We enrolled 128 patients, mean age 61,7 years. Mean HACOR at one hour after starting CPAP was 3,27 ± 3,84 and mean PaO 2 /FiO 2 was 203,30 ± 92,21 mmHg; 35 patients (27,3%) presented CPAP failure: 29 underwent oro-tracheal intubation and 6 died due to COVID-19 (all having a do-not-intubate order). HACOR accuracy for predicting CPAP failure was 82,03%, while PaO 2 /FiO2 accuracy was 81,25%. Conclusion Although HACOR score had a good diagnostic performance in predicting CPAP failure in COVID-19-related ARF, PaO 2 /FiO 2 has also shown to be a good predictor of failure.

Background A high-flow nasal cannula (HFNC) is an alternative device for oxygena-tion, which improves gas exchange and reduces the work of breathing. Postextubation respiratory failure causes increased morbidity and mortality. HFNC has been widely employed during the COVID-19 pandemic. The purpose of this paper is to report a single-centre experience on the effectiveness and safety of HFNC in weaning COVID-19 patients. Methods Nine patients showed severe acute respiratory failure and interstitial pneumonia due to SARS-CoV-2. After mechanical ventilation (5 Helmet CPAP, 4 invasive mechanical ventilation), they were de-escalated to HFNC. Settings were: 34–37°C, flow from 50 to 60 L min -1 . FiO 2 was set to achieve appropriate SpO 2 . Results Nine patients (4 females; age 63 ± 13.27 years; BMI 27.2 ± 4.27) showed a baseline PaO 2 /FiO 2 of 109 ± 45 mm Hg. After a long course of ventilation all patients improved (PaO 2 /FiO 2 336 ± 72 mm Hg). Immediately after initiation of HFNC (2 hours), PaO 2 /FiO 2 was 254 ± 69.3 mm Hg. Mean ROX index at two hours was 11.17 (range: 7.38–14.4). It was consistent with low risk of HFNC failure. No difference was observed on lactate. After 48 hours of HFNC oxygen therapy (day 3), mean PaO 2 /FiO 2 increased to 396 ± 83.5 mm Hg. All patients recovered from respiratory failure after 7 ± 4.1 days. Conclusions HFNC might be helpful in weaning COVID-19 respiratory failure. Effectiveness and comfort should be assessed between 2 and 48 hours. Clinical outcomes, oxygenation, and ROX index should be considered, to rule out the need for intubation. Further evidence is required for firm conclusions.