Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Impact of healthcare-associated infections on functional outcome of severe acquired brain injury during inpatient rehabilitation.

To describe healthcare-associated infections in inpatient neuro-rehabilitation and their impact on functional outcome, a multicenter observational study with severe acquired brain injury (sABI) patients was performed. Patients were divided into infected (INF-group) or not infected (noINF-group) and assessed at admission and discharge, by means of the Glasgow Coma Scale (GCS), the Rancho Los Amigos Levels of Cognitive Functioning Scale (LCF), the Disability Rating Scale (DRS), and the modified Barthel Index (mBI). One hundred-nineteen patients were included in the INF-group, and 109 in the noINF-group. Culture specimens were found positive for bloodstream (43.8%), respiratory tract (25.7%), urinary tract (16.2%), gastro-intestinal system (8.6%) and skin (2.4%) infections. Multiple microorganisms were the most frequent (58.1%) and 55.5% of patients needed functional isolation due to multidrug resistant germs. The functional status of both groups improved after rehabilitation, but multivariable analyses showed that the INF-group showed a significantly lower gain to GCS (p = 0.008), DRS (p = 0.020) and mBI (p = 0.021) compared to the noINF-group. Length of stay (LOS) and number of skipped rehabilitative sessions were not statistically different between the groups; mortality rate was significantly higher in the INF-group (p = 0.04). Infected sABI patients showed longer LOS, significant increased mortality, and a lower functional outcome than not infected patients.

Validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in Internal Medicine wards; a prospective, multicenter study.

BACKGROUND: Few data are available on the validity of "Sepsis-3" criteria in identifying patients with sepsis in internal medicine wards (IMWs). Real-life data about this topic and on the prevalence of sepsis in IMWs could be useful for improving hospital organization. OBJECTIVES: To assess the validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in IMWs. Secondary objectives: to evaluate the prevalence of these patients in IMWs and to compare "Sepsis-3" and "Sepsis-1" criteria. METHODS: Multicenter, prospective, observational, cohort study, carried out in 22 IMWs of Tuscany (Italy). All patients admitted to each of the study centers over a period of 21-31 days were evaluated within 48 hours; those with clinical signs of infection were enrolled. The main outcome was in-hospital mortality. RESULTS: 2,839 patients were evaluated and 938 (33%) met the inclusion criteria. Patients with sepsis diagnosed according to "Sepsis-3" were 522, representing 55.6% of patients with infection and 18.4% of all patients hospitalized; they were older than those without sepsis (79.4±12.5 vs 74.6±15.2 years, p<0.001). In-hospital mortality was significantly higher in patients with sepsis compared to others (13.8% vs 4.6%; p<0.001). "Sepsis-3" criteria showed greater predictive validity for in-hospital mortality than "Sepsis-1" criteria (AUROC=0.71; 95%CI, 0.66-0.77 vs 0.60; 95%CI 0.54-0.66; p=0.0038). CONCLUSIONS: "Sepsis-3" criteria are able to identify patients with community-onset sepsis in IMWs, whose prevalence and in-hospital mortality are remarkably high. Medical departments should adapt their organization to the needs for care of these complex patients.

Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern.

INTRODUCTION: The aim of this study was to evaluate the risk of hospitalization or death in patients infected by SARS-CoV2 variants of concern (VOCs) receiving combinations of monoclonal antibodies (mAbs), bamlanivimab/etesevimab or casirivimab/imdevimab. METHODS: Observational prospective study conducted in two Italian hospitals (University Hospital of Pisa and San Donato Hospital, Arezzo) including consecutive outpatients with COVID-19 who received bamlanivimab/etesevimab or casirivimab/imdevimab from March 20th to May 10th 2021. All patients were at high risk of COVID-19 progression according to FDA/AIFA recommendations. Patients were divided into two study groups according to the infecting viral strain (VOCs): Alpha and Gamma group. The primary endpoint was a composite of hospitalization or death within 30 days from mAbs infusion. A Cox regression multivariate analysis was performed to identify factors associated with the primary outcome in the overall population. RESULTS: The study included 165 patients: 105 were infected by the VOC Alpha and 43 by the VOC Gamma. In the Alpha group, no differences in the primary endpoint were observed between patients treated with bamlanivimab/etesevimab or casirivimab/imdevimab. Conversely, in the Gamma group, a higher proportion of patients treated with bamlanivimab/etesevimab met the primary endpoint compared to those receiving casirivimab/imdevimab (55% vs. 17.4%, p = 0.013). On multivariate Cox-regression analysis, the Gamma variant and days from symptoms onset to mAbs infusion were factors independently associated with higher risk of hospitalization or death, while casirivimab/imdevimab was protective (HR 0.33, 95% CI 0.13-0.83, p = 0.019). CONCLUSIONS: In patients infected by the SARS-CoV-2 Gamma variant, bamlanivimab/etesevimab should be used with caution because of the high risk of disease progression.

Healthcare-Associated Infections in Subjects With Severe Acquired Brain Injury: The Effect of Microbial Colonization on the Functional Outcome. Data From a Multicenter Observational Study.

Background: Hospital-acquired infections (HAIs) and microbial colonization are a worldwide serious threat for human health. Neurological patients with infections who undergo rehabilitation have a significantly poor recovery. The effect of microbial colonization on the functional outcome in severe acquired brain injury (sABI) subjects is still unclear. Aim: The aim of this multicenter observational study was to describe the clinical impact of HAIs and colonization on the functional outcome of sABI subjects admitted to inpatient neurorehabilitation. Methods: Patients were assigned to three groups: infected (INF), not infected (noINF), and colonized (COL). The Glasgow Coma Scale (GCS), the Rancho Los Amigos Levels of Cognitive Functioning Scale, Disability Rating Scale, and modified Barthel Index (mBI) assessments were performed both at admission and discharge. Results: Two hundred sixty-five (92 female/173 male) patients were enrolled: 134 were assigned to INF, 63 to COL, and 68 to noINF. In the INF group, 231 culture specimens were found positive for bloodstream (44.2%), respiratory tract (25.5%), urinary tract (18.6%), gastrointestinal tract (8.3%), skin (3%), and cerebrospinal fluid (0.4%) infections. After rehabilitation, all groups showed a significant improvement in all assessment tests, except for the noINF group that did not show any improvement in GCS. Both noINF and COL groups showed a significantly higher gain in mBI than the INF group (p = 0.000). The COL group showed a significantly higher gain than the noINF group in GCS (p = 0.001). A significantly lower improvement was detected in the INF group than the COL and noINF groups. The rate of patients who needed functional isolation was higher in the INF group than the COL group. Length of stay (LOS) (in days) was 56 ± 50.7, 88.3 ± 55, and 101.3 ± 73.6 for noINF, INF, and COL groups, respectively. The number of deaths in the INF group was significantly higher (24.6%) than the noINF group (7.4%) (p = 0.005) and comparable to the COL group (19%). Conclusion: Colonized sABI patients obtained a similar functional outcome to that of subjects who had no infections, even if they needed a significantly higher LOS.

Analysis of genetic and viral determinants of HBsAg levels in patients with chronic HBV infection.

Single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) gene can influence the course of treated and untreated HBV infection. However, the correlation between different IL28B-SNPs and HBVDNA and quantitative HBsAg (qHBsAg) in chronic HBV infection remains to be fully elucidated. Patients with chronic HBV infection were analysed for qHBsAg, HBVDNA, HBV genotype and six IL28B-SNPs (rs12980275, rs8105790, rs8099917, rs7248668, rs12979860, rs10853728). Seventy patients were recruited: 80% Caucasian, 56% genotype D, 44% treated with nucleos(t)ide analogues, 11% cirrhotic, 37% inactive carriers (IC). Median (IQR) qHBsAg and HBVDNA were 3.2 log10 IU/ml (2.2-3.9) and 2.2 log10 IU/ml (0.3-3.3), respectively. Lower levels of qHBsAg were associated in the whole study population with rs12979860 CC vs. CT (p=0.05), rs12980275 AA vs. AG (p=0.04), rs8105790 TT vs. CT (p=0.05) and genotype D vs. A+E (p=0.01). rs8105790 TT was present in 81% of IC vs. 46% non-IC (p=0.005). These data were also confirmed in the untreated patients' subgroup. In multivariate analysis, IL28B-SNP haplogroups were associated with lower qHBsAg: CC/AA at rs12979860/rs12980275 (-0.70 log IU/mL, 95% CI -1.26;-0.14; p=0.01), CC/TT at rs12979860/rs8105790 (-0.78 log IU/mL, 95% CI -1.33;-0.23; p=0.006) and AA/TT at rs12980275/rs8105790 (-0.71 log IU/mL, 95% CI -1.27;-0.17; p=0.01) both in the whole population and in the untreated subgroup. Specific IL28-SNP haplogroups might be associated with lower qHBsAg.

[Which screening for Leishmania infantum in asymptomatic blood donors?]. / Leishmania infantum e donatori di sangue: quale screening?

Leishmaniasis is a protozoan infection endemic in Italy with a greatly underestimated prevalence. The recent documentation of parasitaemia in blood donors is a cause of concern for blood safety. Because there is no screening against leishmania, we performed a study to assess the presence of protozoa in blood donors of Siena district (Tuscany) during the seasonal activity of the vector. From June to October 2007, 162 patients were screened for Leishmania infantum by indirect immunofluorescence serology (IFAT) and PCR for kinetoplast (kDNA). No subject was positive for antibodies, while 11 samples (6.8%) were positive for kDNA. A second PCR (nested-PCR) was negative for all kDNA positive individuals and other subjects for a total of 55 samples (33% of total subjects). The sequence analysis of three samples positive for kDNA was compatible with mitochondrial DNA. Through the techniques used, we were unable to confirm the presence of leishmania in the blood of the subjects studied. The choice of the diagnostic protocol in blood donors remains an open issue as molecular analysis (kDNA) seems to suggest, in our experience, limits of specificity.