Real-life use of remdesivir-containing regimens in COVID-19: a retrospective case-control study.

Background: Remdesivir (REM) has shown potent antiviral activity in vitro and efficacy in animal models of COVID-19; nevertheless, clinical trials and real-life reports have shown conflicting data on its effectiveness. Aims of the study were to evaluate the impact of remdesivir on I) Intensive Care Unit (ICU) admission, II) need for orotracheal intubation (OTI) and III) in-hospital mortality. Furthermore, we estimated the kinetics of laboratory parameters and assessed the risk factors for in-hospital mortality in the remdesivir population. Methods: We conducted a retrospective, single-center, case-control (1:1) study including hospitalized patients with confirmed SARS-CoV-2 infection. Cases were patients treated with remdesivir for 5 days, controls were patients not receiving remdesivir. Results: A total of 192 patients (96 cases and 96 controls) were included in the study. Patients receiving remdesivir had a lower rate of ICU admission and need for OTI than controls, whereas no difference between cases and controls were observed as for mortality rate. However, at multivariable analysis remdesivir was not associated with ICU admission neither with OTI. Instead, presence of haematological malignancies, lower duration of symptoms, higher severity of infection and low lymphocytes count at admission were independently associated with in-hospital mortality. In patients treated with remdesivir a low albumin value and duration of lymphopenia were significantly associated with mortality. Conclusions: Our real-life study showed that therapy with remdesivir did not have impact on either ICU admission, need for OTI or in-hospital mortality.

Comparison of Thrombotic Events and Mortality in Patients with Community-Acquired Pneumonia and COVID-19: A Multicenter Observational Study.

BACKGROUND: It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival. METHODS: In this multicenter observational cohort study, 1,138 patients, hospitalized for CAP (n = 559) or COVID-19 (n = 579) from seven clinical centers in Italy, were included in the study. Consecutive adult patients (age ≥ 18 years) with confirmed COVID-19-related pneumonia, with or without mechanical ventilation, hospitalized from March 1, 2020 to April 30, 2020, were enrolled. COVID-19 was diagnosed based on the World Health Organization interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events. RESULTS: During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p = 0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses.During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p < 0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6 vs. 13.4% in thrombotic-event-free patients; p < 0.001). In CAP, 13.8% of patients experiencing thrombotic events died versus 1.8% of thrombotic event-free ones (p < 0.001). A multivariable Cox-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (hazard ratio: 2.1; 95% confidence interval: 1.4-3.3; p < 0.001). CONCLUSION: Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.

Candida fracture-related infection: a systematic review.

Background: The aim of this study is to summarize and improve knowledge regarding a Candida fracture-related infection (CFRI) through a systematic review on the topic, accompanied by a case report. Methods: A systematic review and meta-analysis based on PRISMA statement were conducted on the CFRI topic. The following combined search terms were used to explore PubMed, Cochrane, and the Embase database: "fungal infection", "candida", "fracture related infection", "bone infection", "orthopedic infection", "internal fixation", "post-traumatic infection", and "osteomyelitis". Results: Out of 1514 records, only 5 case reports matched the selection criteria and were included. Moreover, a new case of CFRI, not previously described, was reported in this paper and reviewed. The main risk factors for CFRI were open wounds (three cases) and immunodeficiency (three cases). Initial improvement of clinical and laboratory signs of infection was noted in all cases. In the available short-term follow-up (mean 12.1 months; range 3-42), the reoperation rate was 33.3 %. Using a strategy based on extensive debridement/resection methods and prolonged systemic antifungal therapy (mean 8.8 weeks; range 6-18), four of six cases (66.6 %) were cured. Bone union occurred in three out of six cases. Conclusion: There is very low-quality evidence available regarding CFRI. Candida infections in surgically treated fractures are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk; therefore, they still represent a current diagnostic challenge. The existing fracture-related infection treatment algorithm combined with long-term systemic antifungal therapy has an anecdotal value and needs more extensive studies to be validated.

SARS-CoV-2 Among Migrants Recently Arrived in Europe From Low- and Middle-Income Countries: Containment Strategies and Special Features of Management in Reception Centers.

Despite the "migrants and COVID-19" topic has been neglected since felt marginal concerning other aspects of the SARS-CoV-2 pandemic, it represents a relevant public health issue in the European countries. This report describes COVID-19 containment strategies adopted in a large Italian reception center hosting recently arrived asylum-seeker migrants. Risk assessment and prevention measures adopted were described. Geo-spatial epidemiological analysis of the outbreak was reported. Significant gaps in the knowledge of self-protection measures from contagious diseases and in the perception of the pandemic risk were observed in migrants; health promotion activities, targeted to remove cultural barriers and improve behaviors appropriate to individual protection, were able to fulfill this gap. In low-resource settings, especially in closed communities, the implementation of social distancing strategies, the systematic use of individual protection devices, and active syndromic surveillance are essential tools to limit the risk of outbreaks. In the event of an outbreak, it is relevant to rapidly activate containment procedures based on systematic screening, isolation, and quarantine, taking into consideration the limits of tracing contacts within a closed community. Not being able to trace certain contacts, the geo-spatial epidemiological analysis of cases distribution could be key in the management of the outbreak. Interestingly, positive cases identified in our facility were all clinically pauci-symptomatic or asymptomatic. Dedicated strategies are needed to minimize the chance of SARS-CoV-2 transmission in a limited space such as reception centers and a vulnerable population such as migrants.

Persistent Systemic Microbial Translocation and Intestinal Damage During Coronavirus Disease-19.

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.

Role of Serum E-Selectin as a Biomarker of Infection Severity in Coronavirus Disease 2019.

INTRODUCTION: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis. METHODS: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed. RESULTS: One hundred patients were included, with a median age (IQR) of 65 years (58-78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1-35). sE-selectin values did not differ between deceased and survivors (p = 0.06) and among patients with or without a thrombotic event (p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO2/FiO2 < 200 and PaO2/FiO2 200-300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 (p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 (p = 0.004)). CONCLUSIONS: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity.