Background Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H 2 O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H 2 O [25–43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32–1·95] vs 1·90 [1·50–2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001). Interpretation Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dim...

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

Background Preliminary reports have described significant procoagulant events in patients with coronavirus disease-2019 (COVID-19), including life-threatening pulmonary embolism (PE). Main text We review the current data on the epidemiology, the possible underlying pathophysiologic mechanisms, and the therapeutic implications of PE in relation to COVID-19. The incidence of PE is reported to be around 2.6–8.9% of COVID-19 in hospitalized patients and up to one-third of those requiring intensive care unit (ICU) admission, despite standard prophylactic anticoagulation. This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells. Conclusion Thromboprophylaxis should be started in all patients with suspected or confirmed COVID-19 admitted to the hospital. The use of an intermediate therapeutic dose of low molecular weight (LMWH) or unfractionated heparin can be considered on an individual basis in patients with multiple risk factors for venous thromboembolism, including critically ill patients admitted to the ICU. Decisions about extending prophylaxis with LMWH after hospital discharge should be made after balancing the reduced risk of venous thromboembolism (VTE) with the risk of increased bleeding events and should be continued for 7–14 days after hospital discharge or in the pre-hospital phase in case of pre-existing or persisting VTE risk factors. Therapeutic anticoagulation is the cornerstone in the management of patients with PE. Selection of an appropriate agent and correct dosing requires consideration of underlying comorbidities.

Background: Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. Methods: We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. Results: We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. Conclusions: HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. Trial registration: NCT04411459. 15D score 3 months -mean ± SD 0.857 ± 0.133 0.927 ± 0.061 0.800 ± 0.135 0.853 ± 0.114 0.637 ± 0.204 < 0.001 15D score 1 year -mean ± SD 0.880 ± 0.115 0.964 ± 0.033 0.820 ± 0.068 0.866 ± 0.088 0.572 ± 0.112 < 0.001 Mobility -mean ± SD 0.876 ± 0.207 0.963 ± 0.104 0.828 ± 0.191 0.901 ± 0.166 0.375 ± 0.298 < 0.001 Vision -mean ± SD 0.953 ± 0.119 0.992 ± 0.040 0.942 ± 0.108 0.949 ± 0.094 0.681 ± 0.280 < 0.001 Hearing -mean ± SD 0.968 ± 0.098 1.000 ± 0.000 1.000 ± 0.000 0.745 ± 0.135 0.857 ± 0.192 < 0.001 Breathing -mean ± SD 0.746 ± 0.238 0.879 ± 0.154 0.620 ± 0.227 0.753 ± 0.223 0.438 ± 0.238 < 0.001 Sleeping -mean ± SD 0.838 ± 0.238 0.940 ± 0.135 0.716 ± 0.274 0.929 ± 0.142 0.632 ± 0.312 < 0.001 Eating -mean ± SD 0.979 ± 0.102 1.000 ± 0.000 1 .000 ± 0.000 1.000 ± 0.000 0.587 ± 0.221 < 0.001 Speech -mean ± SD 0.980 ± 0.090 0.996 ± 0.032 0.996 ± 0.036 0.948 ± 0.117 0.777 ± 0.276 < 0.001 Excretion -mean ± SD 0.974 ± 0.110 1.000 ± 0.000 1.000 ± 0.000 0.872 ± 0.191 0.720 ± 0.292