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Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Real-life experience with imipenem/cilastatin/relebactam (IMI/REL) for the treatment of KPC-producing Klebsiella pneumoniae complex (KPCKp) and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa (DTR-PA) infections is herein described. Methods: Adult patients with KPC-Kp or DTR-PA infections who received =48 h of IMI/REL were included. Clinical and microbiological outcomes were retrieved through the medical records. Primary outcome was clinical cure. Secondary outcomes included mortality from infection onset and adverse effects attributable to IMI/REL. Results: We included 10 patients with different infections caused by DTRPA (n = 4), KPC-Kp [n = 5, of which 3 ceftazidime/avibactam-resistant (CTV-R KPC-Kp), 2 CTV susceptible (CTV-S KPC-Kp)] or both DTR-PA/KPC-Kp (n = 1) successfully treated with IMI/REL: 3 hospital-acquired pneumonia, 1 ventilatorassociated pneumonia, 2 skin and soft tissue infections, 1 osteomyelitis, 2 bloodstream infections, 1 complicated urinary tract infection. Clinical cure was achieved in all cases. No patients died and no side effect were reported. Discussion: We reported the preliminary real-life experience on the successful and safe use of IMI/REL for the treatment of KPC-Kp or DTR-PA complicated infections, including pneumonia and bone infections. [ABSTRACT FROM AUTHOR]

Background: Since the beginning of 2020, the SARS-CoV-2 pandemic has become a serious public health problem. Numerous studies have highlighted the main clinical features of COVID-19, mainly the huge heterogeneity of the clinical manifestations that can vary from asymptomatic infection to serious viral pneumonia with a high mortality rate. The aim of this study was to analyze retrospectively the clinical characteristics and assess the risk factors for mortality in an Italian cohort of patients with COVID-19., Methods: Retrospective analysis including patients with COVID-19 admitted to the Infectious Diseases wards of Azienda Ospedaliera Universitaria Policlinico "Umberto 1", Rome, from March 2020 to May 2020. The data were part of an electronic anonymous web-based database processed by SIMIT (Italian Society of Infectious and Tropical Diseases)., Results: 258 patients were included in the analysis, and 34 (13.2%) died. The median age was 62 (IQR, 52-74), 106 (40%) were women, and 152 (60%) were males, 172 (66.7%) had at least one co-morbidity. The most common signs and symptoms were: fever [221 (85.6%)], cough [135 (52.3%)], and dyspnea [133 (51.5%)]. The PaO2/FiO2 ratio was often altered [352 (IQR, 308-424)]. Lymphopenia [lymphocyte counts, 875/μL (IQR, 640-1250)] and high levels of D-dimer [mg/dL, 874 (IQR, 484-1518)] were found. Non-survivors were older than survivors [median age, 74 (IQR, 67-85)] vs. 61 (QR, 51-72)], mostly men [25 (73.5%)] and more frequently with more than 2 comorbidities [21 (61.8%) vs. 94 (42.1%)]. In the multiple logistic regression model, the variables associated with in-hospital mortality were age [OR, 3.65 (95% CI, 1.22-10.89)], male gender [OR, 2.99 (95% CI, 1.18-7.54)], blood urea [OR, 2.76 (95% CI, 1.20-6.35)] and a low PaO2/FiO2 ratio [OR, 0.28 (95% CI, 0.12-0.62)]., Conclusion: The mortality rate in COVID-19 was 13,2%. The risk factors associated with in-hospital mortality were advanced age, male sex, increased blood urea, and the PaO2/FiO2 ratio reduction.

Convalescent plasma (CP) therapy might be effective in patients with haematological malignanciesand B-cell depletion. We report a single-centre experience of COVID-19 patients with non-Hodgkinlymphoma and absence of B-cells as a consequence of anti-CD20 therapy successfully treated withCP from October 2020 to May 2021. CP was given in the presence of pneumonia with respiratoryfailure despite standard treatment and consisted of three infusions on an alternate-day basis. A reviewof the current literature on this topic was also performed. Six patients were identified (medianage 59.5 years (range 50-73)). The last anti-CD20 drug administration occurred 60 days before infection(range 0-360). CP was administered after a median of 51 days (range 9-120) from SARS-CoV-2diagnosis, with an early improvement in all but one subject. We suggest a possible clinical benefitof convalescent CP treatment in COVID-19 patients with haematological malignancies and B-celldepletion having persistent/recurrent pneumonia.

Introduction: There is the need of a simple but highly reliable score system for stratifying the risk of mortality and Intensive Care Unit (ICU) transfer in patients with SARS-CoV-2 pneumonia at the Emergency Room., Purpose: In this study, the ability of CURB-65, extended CURB-65, PSI and CALL scores and C-Reactive Protein (CRP) to predict intra-hospital mortality and ICU admission in patients with SARS-CoV-2 pneumonia were evaluated., Methods: During March-May 2020, a retrospective, single-center study including all consecutive adult patients with diagnosis of SARS-CoV-2 pneumonia was conducted. Clinical, laboratory and radiological data as well as CURB-65, expanded CURB-65, PSI and CALL scores were calculated based on data recorded at hospital admission., Results: Overall, 224 patients with documented SARS-CoV-2 pneumonia were included in the study. As for intrahospital mortality (24/224, 11%), PSI performed better than all the other tested scores, which showed lower AUC values (AUC=0.890 for PSI versus AUC=0.885, AUC=0.858 and AUC=0.743 for expanded CURB-65, CURB-65 and CALL scores, respectively). Of note, the addition of hypoalbuminemia to the CURB-65 score increased the prediction value of intra-hospital mortality (AUC=0.905). All the tested scores were less predictive for the need of ICU transfer (26/224, 12%), with the best AUC for extended CURB-65 score (AUC= 0.708)., Conclusion: The addition of albumin level to the easy-to-calculate CURB-65 score at hospital admission is able to improve the quality of prediction of intra-hospital mortality in patients with SARS-CoV-2 pneumonia., Competing Interests: Competing interests The authors declare no financial and non-financial competing interests., (Copyright © 2016 - 2021 InfezMed.)