IntroductionThe Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU.MethodsIn this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analysed. Data were collected including medication, mode and usage of the NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths.ResultsForty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean age was 68 (sd 13) years. The PaO2/FiO2 ratio at baseline was 152±79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression.ConclusionsThe application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.

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 This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P &lt; 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P &lt; 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P &lt; 0.001). Conclusion Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.

We report a case of late-onset pulmonary fibrosis involving the upper lobes that occurred in a young man treated with bleomycin for mediastinal germ-cell carcinoma. The parenchymal lesions became clinically apparent about two years after chemotherapy had been completed, with a slowly progressive course and sparing the lower lung fields during follow-up. Other possible diagnoses could be excluded on the basis of the patient's clinical history, laboratory tests and pathological findings.

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A hypercoagulability state with fatal thrombosis events seems to characterize the clinical worsening of COVID-19 pneumonia. The benefit and safety of anticoagulant doses of low molecular weight heparin (LMWH) in COVID-19 are still unknown. We evaluated in a retrospective cohort study 257 COVID-19 patients consecutively admitted to our COVID-Hospital from February 29, to April 7, 2020. We compared the in-hospital mortality between patients treated with prophylactic or therapeutic doses of LMWH. Of the 257 patients enrolled, 49 (19.1%) died during the hospitalization. Hospital mortality was significantly lower in patients treated with therapeutic doses of LMWH (enoxaparin 70-100 I.U./kg twice daily) (17/126, 13.5%), than in patients treated with prophylactic doses (60-90 I.U./kg once daily) (32/131, 24.4%; χ²=4.98, p = 0.02). In a stratified analysis by ventilation type, the only subgroup of patients who benefited from therapeutic LMWH was that requiring noninvasive mechanical ventilation (OR=0.099, 95% CI 0.028-0.354, p<0.001). No fatal bleedings were observed. In this retrospective study the treatment with therapeutic LMWH is safe and seems to reduce mortality in COVID-19 patients, especially among those who need noninvasive mechanical ventilation. Authors Daniela Aschieri and Marco Stabile contributed equally to this work.

Objective To evaluate the role of low molecular weight heparin in COVID-19 treatment.Design Retrospective cohort studySetting Patients with COVID-19 pneumonia consecutively admitted to Castel San Giovanni COVID- Hospital from February 29, to April 7, 2020.Main outcome measure Hospital mortality and safety in patients treated with low molecular weight hep- arin.Results Of the 257 patients enrolled, 49 (19.1%) died during the hospitalization. Hospital mortality was significantly lower in patients treated with therapeutic dose of low molecular weight heparin (T-LMWH) (17/126, 13.5%), compared with patients treated with prophylactic dose (P-LMWH) (32/131, 24.4%; χ²=4.98, p = 0.02). Crude and adjusted odds ratios of mortality for patients treated with T-LMWH were OR=0.483, 95% CI 0.252-0.923 and OR=0.374, 95% CI 0.177-0.792. In a stratified analysis by ventila- tion type, the only subgroup of patients who benefited from therapeutic doses of heparin were those re- ceiving non-invasive mechanical ventilation (OR=0.099, 95% CI 0.028-0.354, p<0.001). No fatal bleed- ings were observed.Conclusion Treatment with therapeutic doses of T-LMWH is safe and seems to reduce mortality in COVID-19 patients with pneumonia, especially among those who need non-invasive mechanical ventila- tion. We look forward to prospective studies to confirm this observation and evaluate the appropriate dose of LMWH in the treatment of COVID-19 patients.