Circulating Small RNA Profiling of Patients with Alveolar and Cystic Echinococcosis.

Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.

Characteristics of COVID-19 vaccinated and unvaccinated patients admitted to Careggi University Hospital, Florence, Italy.

More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0%, breakthrough infections are common and may lead to severe outcome in fragile population. We conducted a real-world observational study on 420 COVID-19 admitted patients from July 2021 to January 2022 in a tertiary level Italian hospital. We collected patient's vaccination and SARS-CoV-2 serological status, SARS-CoV-2 treatments, oxygen supports, intensive (ICU) and subintensive (sub-ICU) care unit admissions, length of staying (LoS) and in-hospital mortality. One-hundred-seventy-two vaccinated and 248 unvaccinated patients were admitted during the study period. Vaccinated group (Vg) had a significantly more elevated Charlson Comorbidity Index than Unvaccinated group (UVg), and no statistical differences were found in terms of in-hospital mortality, LoS or ICU and sub-ICU admissions. Among Vg, anti-S antibodies were detected in 86.18% of patients (seropositives). Vaccinated seronegative patients' in-hospital mortality was significantly higher than vaccinated seropositive patients (33.33% vs 10.69%, p = 0.0055): in particular, mortality rate in 45-69 years old population was higher in vaccinated seronegative group, and comparable in patients ≥ 70 years old. No differences in terms of outcome were registered between Vg and UVg, taking into account that Vg was considerably older and with more comorbidities. In line with other recent observations, higher mortality rate was evidenced for seronegative vaccinated patients. Primary prophylaxis and early treatments result to be necessary, especially for older and immunosuppressed populations.

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.

Implementing Early Phase Treatments for COVID-19 in Outpatient Settings: Challenges at a Tertiary Care Center in Italy and Future Outlooks.

We present a brief commentary illustrating the current COVID-19 outpatient treatment options in Italy. We also report our experience setting up a service dedicated to these patients in the wake of the rise in COVID-19 cases observed in January 2022. We also gathered data on the daily costs faced by our outpatient service, based at a tertiary care center located in Florence, Italy. We present them with some considerations on future outlooks on the use of outpatient treatment in COVID-19.

Treatment with anti-SARS-CoV-2 monoclonal antibodies in pregnant and postpartum women: first experiences in Florence, Italy.

PURPOSE: Pregnant and postpartum women are at increased risk of developing severe COVID-19. Monoclonal antibodies (mAbs) are now widely used in high-income countries to treat mild to moderate COVID-19 outpatients at risk for developing severe disease. Very few data are available on the use of mAbs in special populations, including pregnant and postpartum women. Here we present our early experience with mAbs in these two populations. METHODS: Electronic records of pregnant and postpartum women treated with mAbs at Careggi University Hospital, Florence, were retrieved. Relevant data were extracted (age, presence of risk factors for COVID-19, oxygen support, mAb type, gestational age, and pregnancy status). When available, outcomes at 28 days after administration were also included. RESULTS: From March 1st to September 30th 2021, eight pregnant and two postpartum women have been treated with mAbs at our center. The median age was 31 years (IQR 30-33.5, range 29-38), median gestational age was 24 weeks. Seven patients had additional risk factors. According to the Italian disposition, all patients received casirivimab/imdevimab, with five receiving a 2.4 mg dose and five receiving a 8 g dose. Eight patients improved. One developed myocarditis, considered a COVID-19 complication. Another required a transient increase of low flow oxygen support before improving and being discharged. At a 28 days follow-up, all patients were clinically recovered. We did not observe mAbs related adverse events. CONCLUSION: Although preliminary data should be interpreted with caution, it is remarkable how mAbs were well tolerated by pregnant women with COVID-19. Further data on mAbs in this special population should be collected but the use of mAbs in pregnant and postpartum patients should be considered. Even thus oral antivirals are becoming available, they are not recommended in pregnant and postpartum women. This population may specifically benefit from treatment with last generation mAbs.

Letter to the Editor Regarding Management of Adult Patients with COVID-19 Outside Intensive Care Units: Guidelines from the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

Recently, the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) published guidelines on the management of inpatients with COVID-19. The guidelines do not recommend the use of monoclonal antibodies (mAbs) in inpatients, pending results from clinical trials. However, recently the Italian Drug Agency (AIFA) has allowed for the use of casirivimab/imdevimab at higher doses in hospitalized seronegative patients with COVID-19. Furthermore, several other therapeutic options based on mAbs are about to become available for outpatients. Here we provide a brief summary of the future possibilities and summarize existing data.