Key PointsQuestionWhat are the baseline characteristics and outcomes of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to intensive care units (ICUs) in Lombardy, Italy?FindingsIn this retrospective case series that involved 1591 critically ill patients admitted from February 20 to March 18, 2020, 99% (1287 of 1300 patients) required respiratory support, including endotracheal intubation in 88% and noninvasive ventilation in 11%; ICU mortality was 26%.MeaningIn this case series of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed coronavirus disease 2019 (COVID-19), a high proportion required mechanical ventilation and ICU mortality was 26% as of March 25, 2020.

IMPORTANCE Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). OBJECTIVE To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. DESIGN, SETTING, AND PARTICIPANTS This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. EXPOSURES Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. MAIN OUTCOMES AND MEASURES Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. RESULTS Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (FiO 2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low PaO 2 :FiO 2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). CONCLUS...

Background COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.Methods We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.Findings All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.Interpretation The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.

Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population. RESEARCH DESIGN AND METHODS In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020. RESULTS Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29-0.66]; P 5 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P 5 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P 5 0.0008) compared with patients receiving standard of care, respectively. CONCLUSIONS In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.