Background No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment.Methods This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. FindingsOf 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0•41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0•0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0•61, 95% CI 0•40-0•92; p=0•020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0•0001).Interpretation Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia.

Background In this study we evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical coronavirus disease 2019 (COVID-19) and evaluated different case definitions of invasive aspergillosis. Methods Prospective, multicentre study on adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA). Results A total of 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) of patients after a median of 4 (2-8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significant higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, p= 0.002) or PIPA (74% vs 26%, p&lt;0.001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA [OR 3.53 (95%CI 1.29-9.67), P=0.014] or PIPA [OR 11.60 (95%CI 3.24-41.29) p&lt;0.001] with 30-day mortality from ICU admission was confirmed even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients, 43%) A trend toward lower mortality (46% vs 59% p=0.30) and reduction of galactomannan index in consecutive samples was observed. Conclusion We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease

In areas with a low prevalence of MDR bacteria.

KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.