Background Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives To identify predictors of superinfections in COVID-19. Methods Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. Results Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). Conclusions The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.

Objectives To evaluate the impact of low molecular weight heparin (LMWH) on the outcome of patients with SARS-CoV-2 pneumonia. Methods Prospective observational study including consecutive patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (4th March-30th April 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe ARDS. LMWH, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox-regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent Propensity-score (PS) was calculated and a PS-matching performed for each treatment variable. Results Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) hydroxychloroquine, 201 (63.8%) proteases inhibitors, 150 (47.6%) doxycycline, 141 (44.8%) steroids, 42 (13.3%) macrolides, 40 (12.7%) baricitinib, 13 (4.1%) tocilizumab, and 13 (4.1%) remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (HR 0.36 [95% CI 0.21-0.6], p<0.001) and composite endpoint (HR 0.61 [95% CI 0.39-0.95], p=0.029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in Covid-19. Randomized controlled trials are warranted to confirm these preliminary findings.

Acute heart failure is a common condition among adults presenting with dyspnea in the Emergency Department (ED), still the diagnosis is challenging as objective standardized criteria are lacking. First line work-up, other then clinical findings, is nowadays made with lung ultrasound imaging study, chest X-ray study and brain natriuretic peptide (BNP) level determination; however, it is not clear which is the best diagnostic test to be used and whether there is any real benefit for clinical judgement. We set up this study to compare the performances of these three diagnostic tools; furthermore, we combined them to find the best possible approach to dyspneic patients. This is a prospective observational study based in the ED. We enrolled adults presenting with dyspnea not trauma-related, they underwent lung ultrasound, and chest X-ray studies, and NT pro-BNP level determination. Then we compared the results with the diagnosis of acute heart failure established by an independent panel of experts. 236 patients were enrolled in the study. We find sensitivity and specificity for lung ultrasound of 57.73 and 87.97 %, for chest X-ray 74.49 and 86.26 %, for NT pro-BNP 97.59 and 27.56 %, respectively. Combining together the chest X-ray and lung ultrasound, we find the best overall performance with 84.69 % sensitivity, 77.69 % specificity and 87.07 % negative predictive value. From our results, we could not identify the "best test" to diagnose acute heart failure in an emergency setting, although we could suggest that a stepwise workup combining chest X-ray and lung ultrasound at first, then for those negative, a determination of NT pro-BNP assay would be a reasonable approach to the dyspneic patient.

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.

This was a single-center, observational, prospective study designed to compare the effectiveness of a real-time, ultrasound- with landmark-guided technique for subclavian vein cannulation. Two groups of 74 consecutive patients each underwent subclavian vein catheterization. One group included patients from intensive care unit, studied by using an ultrasound-guided technique. The other group included patients from surgery or emergency units, studied by using a landmark technique. The primary outcome for comparison between techniques was the success rate of catheterization. Secondary outcomes were the number of attempts, cannulation failure, and mechanical complications. Although there was no difference in total success rate between ultrasound-guided and landmark groups (71 vs. 68, p = 0.464), the ultrasound-guided technique was more frequently successful at first attempt (64 vs. 30, p < 0.001) and required less attempts (1 to 2 vs. 1 to 6, p < 0.001) than landmark technique. Moreover, the ultrasound-guided technique was associated with less complications (2 vs. 13, p < 0.001), interruptions of mechanical ventilation (1 vs. 57, p < 0.001), and post-procedure chest X-ray (43 vs. 62, p = 0.001). In comparison with landmark-guided technique, the use of an ultrasound-guided technique for subclavian catheterization offers advantages in terms of reduced number of attempts and complications.