BackgroundIntravenous hyper-immune anti-cytomegalovirus immunoglobulins (CMV-IG) therapy are licensed for prophylaxis, yet their therapeutic value in established CMV disease remains poorly defined. We aimed to evaluate the clinical and virological impact of adjunctive CMV-IG in combination with standard antiviral therapy in immunocompromised patients with CMV disease, compared with standard antiviral therapy alone.MethodsWe performed a single-center retrospective case-control study at A.O.U. "Federico II" University Hospital, Naples, Italy, including consecutive immunocompromised patients with CMV disease between March 2021 and November 2024. Cases received standard antiviral therapy plus CMV-IG (100 IU kg-1 day-1 for three consecutive days). Controls received antivirals only.ResultsThirty-four patients were analyzed (15 cases, 19 controls). Thirty-day survival was 93% vs 95% (p=>0.9) and composite outcome (combination of 30-day mortality and clinical response) occurred in 93% vs 90% (p=>0.9) in cases and controls, respectively. Median time-to-virological response in days was achieved 4 vs 7 days (p=<0.001), as was median duration of antiviral therapy in days 12 vs 16 days (p=0.001) and hospitalization 14 vs 19 days (p=0.004) in cases and controls, respectively. Adverse-event rates were low and comparable in the 2 groups.ConclusionsIn this real-world cohort, adjunctive CMV-IG did not affect mortality, but was associated with faster virological clearance and shorter antiviral and hospital courses, without additional toxicity.

Patients with inflammatory bowel disease(IBD)have a higher risk of varicella zoster virus infection (VZI) than the general population, largely due to immunosuppressive-biologic therapies. Preventing viral reactivation is a relevant clinical goal. The recombinant zoster vaccine (RZV, Shingrix) has shown high efficacy and good tolerability in the general population,but data in IBD are limited. Real-world evidence on its effectiveness and safety is needed to support vaccination strategies and guide clinical practice. The objective of the study was to assess the effectiveness and safety of the RZV in IBD. From March 2023 to September 2024, consecutive IBDpatients who received the RZV Shingrix before starting or with ongoing biologics were prospectively enrolled across 9 tertiary IBDcenters. Effectiveness was assessed clinically and defined as the absence of VZI or HZ reactivation during the observation period. Safety outcomes included the occurrence of vaccine-related adverse events (AEs)—such as fever, arthralgia, and others—systematically recorded during the follow-up after each vaccine dose. A total of 420 IBD cases were included, comprising 215 (51.2%) with UC and 205 (48.8%) with CD. Most patients (95.8%) completed the VZV vaccination cycle. Biologic therapy was ongoing in 319 (75.9%) patients, more frequently in CD than UC (p < 0.001). During a mean follow-up of 11.0 ± 1.2 months, VZV reactivation occurred in only 0.7% of patients, confirming a high clinical effectiveness of RZV in IBD. Overall, AEs were reported in 52.4% of cases, with the most common being arm pain (37.1%), followed by asthenia (16.0%) and fever (13.8%). No significant differences between UC and CD (54.4% vs 50.2%, p = 0.448), as for gender (p = 0.96), were found. AE occurrence was significantly associated with ongoing biologic therapy (56.9% vs 29.3% without, p = 0.009) and lower age (median 42 vs 45.5 years, p = 0.047). However, analyzing therapies by specific mechanism of action, no class of drug was associated with a higher AE risk compared to others. Logistic regression confirmed only biologics as an independent risk factor (OR1.84; 95%; p = 0.009). In the subgroup analysis comparing biologics to conventional or no therapy, only asthenia and joint pain were more common in patients on biologics (p < 0.001 and p = 0.04, respectively). No serious AEs were reported. RZV demonstrated a favorable safety profile in IBD patients, with only mild and self-limiting adverse events, more frequently observed in those receiving biologics. Notably, the very low rate of VZV reactivation (0.7%) over a mean follow-up of 11 months confirms the high effectiveness of RZV in this high-risk population. These findings support the integration of RZV into preventive strategies in IBD, particularly before or during immunosuppressive therapy. References: 1. Din S, Selinger CP, Black CJ, Ford AC. Systematic review with network meta-analysis: Risk of Herpes zoster with biological therapies and small molecules in inflammatory bowel disease. Aliment Pharmacol Ther. 2023 Mar; 57 (6): 666-675. 2. Nugent Z, Singh H, Targownik LE, Bernstein CN. Herpes Zoster Infection and Herpes Zoster Vaccination in a Population-Based Sample of Persons With IBD: Is There Still an Unmet Need? Inflamm Bowel Dis. 2019 Feb 21; 25 (3): 532-540. Conflict of interest: Castiglione, Fabiana: Honoraria from: Takeda, AbbVie, Celltrion, Johnsson Johnsson, Cadigroup, Sandoz, Pfizer, Lilly, Lionhealth, Nestlè Guarino, Alessia Dalila: No conflict of interest Pinchera, Biagio: No conflict of interest Spadaro, Giuseppe: No conflict of interest Zappulo, Emanuela: No conflict of interest Calabrese, Giulio: No conflict of interest Rispo, Antonio: None Testa, Anna: Consultant /Advisory board for Abbvie, J & J, Takeda, Ferring Nardone, Olga Maria: Advisory board fees from Eli Lilly, Nestlè, Janssen Speaker fees from AbbVie, Janssen, Eli Lilly, Ferring, Alfa Sigma, Recordati, Noòs, and Pfizer Mucherino, Caterina: Takeda, Pfizer, Alfasigma, Galapagos, Johnson & Johnson, Miranda, Agnese: No conflict of interest Vespere, Giuliana: none Imperatore, Nicola: None to declare Capone, Pietro: No conflict of interest Patturelli, Marta: No conflict of interest Gravina, Antonietta Gerarda: Gravina AG has conducted training activities [e.g. educational continuing medical activities (ECM), preceptorship] for Pfizer, Galapagos Biopharma, and AbbVie. Pellegrini, Lucienne: No conflict of interest Gentile, Ivan: No conflict of interest

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021-2025). Patients received either caspofungin or posaconazole as PAP based on the drug-drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies.

Stenotrophomonas maltophilia bloodstream infection (SM-BSI) carries high mortality and limited therapeutic options. We conducted a single-center retrospective cohort of adults with first SM-BSI (2018-2024) to describe treatment patterns and identify factors associated with survival. Demographic, clinical, and microbiological data were extracted and analyzed. Forty-three patients were included (median age: 63 years; 61% male). Appropriate antimicrobial therapy was given to 74%; trimethoprim-sulfamethoxazole-based regimens were used in 61%; and combination therapy in 23%. The median time from BSI to treatment initiation was 4 days (IQR: 3-5) and the treatment duration averaged 7 days (IQR: 0-12). Thirty-day mortality was 37% (16/43). The survival analysis found that a 14-21-day course was associated with better 30-day survival than a 7-13-day course (0/9 vs. 5/15 deaths; log-rank p = 0.045), whereas monotherapy and combination therapy did not differ (p = 0.855). Multidrug resistance was linked to worse survival (log-rank p = 0.001). In multivariable models for 30-day mortality, only active treatment (aHR: 0.14; 95% CI: 0.02-0.88) and microbiological cure (aHR: 0.08; 95% CI: 0.01-0.47) remained independently protective. These data suggest that outcomes in SM-BSI are driven primarily by the receipt of appropriate therapy and achievement of microbiological clearance, reinforcing the need for prompt source control, optimized antimicrobial treatment, and continued development of novel therapeutic strategies to improve outcomes in this challenging infection.

Bruton tyrosine kinase inhibitors (BTKi) and the BCL-2 inhibitor venetoclax have significantly improved the prognosis of patients with chronic lymphocytic leukemia (CLL). However, the incidence of severe infections in patients receiving these agents needs to be better understood. Our review aimed to provide an overview of grade ≥3 infections in patients with CLL who received BTKi and venetoclax-based therapy in prospective trials. Infection rates were influenced by the age of patients and the duration of follow-up. For treatment-naive (TN) patients receiving BTKi, infection rates ranged between 11.4% and 27.4% and were close to 30% in relapsed/refractory (R/R) patients. TN and R/R patients receiving fixed-duration venetoclax-based treatments showed variable rates, with maximum values around 20%. Opportunistic and fatal infections were uncommon. In conclusion, infections remain a concern in patients with CLL receiving targeted agents. A better definition of factors increasing infection vulnerability could help identify those patients who require infection prophylaxis.

CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.

Introduction Bone mineral density (BMD) is reduced in patients with human immunodeficiency virus (HIV) infection. Trabecular bone score (TBS) is an additional feature calculated by dual-energy X ray absorption (DXA) that measures texture inhomogeneity at lumbar spine level, providing an index of bone microarchitecture. However, its clinical value still needs to be fully addressed. Aims of the study were to assess BMD and TBS in a cohort of patients with HIV compared to a population of healthy subjects and to investigate the prognostic value of TBS in HIV infected patients. Method Bone health was assessed by DXA in 165 patients with HIV infection (120 men, mean age 40 ± 7 years) and in 164 healthy subjects (53 male, mean age 37 ± 10 years). BMD was measured at level of lumbar spine (L1-L4), femoral neck and total hip. TBS was computed from the images of lumbar spine using machine proprietary software. Results BMD at femoral neck level was similar in HIV infected patients and healthy subjects (p = 0.57), whereas BMD measured in total femur was lower in HIV infected patients compared to healthy subjects (p < 0.05). Although mean BMD in lumbar spine was similar between HIV infected patients and healthy subjects (p = 0.90), mean lumbar TBS was lower in patients with HIV infection compared to healthy subjects (p < 0.05). Age, sex and HIV infection resulted independent predictors of reduced TBS. In HIV infected patients age, sex and protease inhibitor duration resulted independent predictors of reduced TBS. TBS was a significant predictor of vertebral fractures during follow-up (p < 0.05). Conclusion Patients with HIV infection have a significant reduction of TBS, a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement.

Pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab in immunocompromised patients has reduced the risk of breakthrough infection, disease, hospitalization, and COVID-19 related mortality. However, the advent of the Kraken variant (XBB.1.5) has limited the use of this monoclonal antibody, based on poor efficacy in in vitro studies The objective of the study was to evaluate the risk of breakthrough infection, symptomatic disease, hospitalization, intensive care admission, and COVID-19 related death in kidney transplant recipients receiving pre-exposure prophylaxis with Tixagevimab/Cilgavimab for COVID-19 in the era of the Kraken variant (XBB.1.5). In a prospective, observational study, we enrolled kidney transplant patients undergoing pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab at the Division of Infectious Diseases of Federico II University of Naples from February 2023 to August 2023. Each patient subsequently underwent a six-month follow-up with symptom monitoring and surveillance nasopharyngeal swab for SARS-CoV-2 RNA detection every 30 days, regardless of symptoms. Thirty-four kidney transplant patients were enrolled, and in the follow-up period only one tested positive for the nasopharyngeal swab for SARSCoV-2 research with asymptomatic infection and virological recovery on the eighth day after diagnosis of infection. Therefore, no patient developed disease, no patient needed hospitalization, and no death occurred. No adverse drug reaction to Tixagevimab/Cilgavimab occurred. Our data, although derived from a limited and uncontrolled sample, show the potential of Tixagevimab/Cilgavimab as a valid and viable therapeutic strategy in pre-exposure prophylaxis for immunocompromised patients. These findings highlight the importance of conducting clinical studies on this topic.

Objective Our objective was to evaluate the safety and efficacy of casirivimab/imdevimab therapy in pregnant women with severe coronavirus disease 2019 (COVID-19) requiring oxygen therapy. Study Design This was a prospective case series study aimed to evaluate the safety and efficacy of casirivimab/imdevimab therapy in unvaccinated pregnant women with severe COVID-19. Inclusion criteria were severe acute respiratory syndrome coronavirus 2 infection documented with polymerase chain reaction, pregnancy, severe COVID-19 requiring oxygen therapy, duration of symptoms of 10 days or less, and able to provide informed consent. Vaccinated women and those with mild-to-moderate disease were excluded from the study. Included patients received casirivimab and imdevimab as a single intravenous dose of 4,000/4,000 mg. Women were also treated with low molecular weight heparin, steroids, and antibiotics, if necessary. The primary outcome was maternal death. Secondary outcomes were the rate of adverse events during infusion or within 72 hours and the rate of abortion. Results Thirteen hospitalized unvaccinated pregnant women with severe COVID-19 requiring oxygen and treated with casirivimab/imdevimab were included in the study. We observed no maternal death, and no patients required intubation or admission to the intensive care unit. No abortion or fetal loss was recorded. Nine pregnancies were still ongoing, and there were three cesarean deliveries and one vaginal delivery. Two were preterm deliveries (at 31 and 34 weeks), and two were term deliveries. Conclusion Casirivimab/imdevimab therapy may be considered as a therapy in unvaccinated pregnant women with severe COVID-19.

Abstract Introduction Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good’s syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS. Methods Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations. Results Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher’s exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS. Conclusions Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols.

Background:HCV-related liver disease is an important cause of morbidity and mortality in patients with HIV infection. It is well known that the response rates to HCV therapy are similar between HCV-monoinfected patients and HIV-HV coinfected ones. The aim of this study was to evaluate the impact of HCV eradication on CD4 + T cell count in a population of HIV-HCV coinfected patients.Materials and Methods:We enrolled patients with HIV-HCV coinfection attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from January 2016 to February 2019, treated with ART (AntiRetroviral Therapy) and DAAs (Direct Antiviral Agents). For each patient, we evaluated HIV and HCV viral load and CD4+ T cell count before starting therapy with DAAs, by SVR12 time and by SVR48 time. Fibrosis was evaluated by the mean of Fibroscan®.Results:Fifty-two patients were enrolled, 40 males. Fibrosis score was F0-F3 in 15 patients and cirrhosis in the remaining 11 (all in Child-Pugh class A). All had been receiving ART, and all were treated with DAAs. Only patient who had not achieved HIV viral suppression for non-compliance also experienced a relapse of HCV infection after the end of DAAs. In all patients, we observed that the CD4+ T cell count at baseline did not show significant variations compared to SVR12 and SVR48 time. We also assessed CD4 count in relation to HIV categories and stage of liver disease, see Table 1. Also, based on the assessments of the subclasses considered, there were no significant changes in the CD4 + T cell count.Conclusion:Our study shows that HCV viral eradication obtained with DAAs in patients with HIV-HCV coinfection is not associated with significant changes in the CD4 + T cell count, regardless of CDC category and stage of liver disease.

The gut microbiota plays a fundamental role in Hepatitis C Virus (HCV)-related liver disease. Indeed, HCV infection alters the gut microbiota, whereas intestinal dysbiosis induces an underlying inflammatory state. This status may lead to liver disease progression. The advent of direct acting antivirals (DAAs) was a turning point in the history of HCV infection, which enhances the chances of recovery. Beyond the elimination of the virus, DAA therapy can affect the gut microbiota of the HCV patient. The study of the gut microbiota in the patient with HCV-related liver disease could be the first step in understanding the etiopathogenesis of hepatopathy thereby opening the way to new therapeutic opportunities. Herein we evaluate current knowledge regarding the gut microbiota in patients with HCV infection and the impact of DAA therapy.

Since 2020, COVID-19 pandemic has spread worldwide causing a huge number of cases and casualties. Among direct anti SARS-CoV-2 agents available for the treatment of COVID-19, only remdesivir and casirivimab/imdevimab have been approved for severe disease. As they act at different levels in blocking viral replication, it is theoretically possible to combine them. In this case series we describe tolerability, safety and effectiveness in a small group of 14 patients of the combination of casirivimab/imdevimab monoclonal antibodies with the polymerase inhibitor remdesivir for the treatment of severe COVID-19. We conducted a retrospective study among consecutive patients admitted to the Infectious Disease ward of the University of Naples (Italy) Hospital for COVID-19 that received the combination of casirivimab/imdevimab and remdesivir for the treatment of severe COVID-19 from the August 1, 2021 to the November 30, 2021. During the study period, 78 patients were admitted for severe COVID-19. Fourteen patients (18%) received the combination casirivimab/imdevimab and remdesivir. They were five males and nine females with a median age of 54 years. Eight patients had significant comorbidities; three patients were in the immediate post-partum period. No adverse drug reaction was observed. All patients except one improved clinical condition and respiratory parameters within seven days following the therapy. All patients were discharged in good conditions.

The intestinal microbiota plays a fundamental role in physiological homeostasis as well as in pathologic conditions. Hepatitis C virus is the leading cause of chronic liver diseases worldwide. The treatment of this infection has been revolutionized by the availability of direct-acting antiviral agents which guarantee a high rate (about 95%) of viral clearance. Few studies have assessed the change in the gut microbiota of patients treated with direct-acting antiviral agents against HCV, and many aspects still need to be clarified. The aim of the study was to evaluate the effects of antiviral therapy on gut microbiota. We enrolled patients with HCV-related chronic liver disease attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples from January 2017 to March 2018 and treated with DAAs. For each patient, a fecal sample was collected and analyzed for the assessment of microbial diversity before the start of therapy and by SVR12 time. We excluded patients who had received antibiotics in the previous 6 months. Twelve patients were enrolled (6 male, 8 genotype 1 (1 subtype 1a), 4 genotype 2). Fibrosis scores were F0 in 1 patient, F2 in 1 patient, F3 in 4 patients and cirrhosis in the remaining 6 (all in Child-Pugh class A). All were treated with DAAs for 12 weeks (5 with Paritaprevir-Ombitasvir-Ritonavir-Dasabuvir, 3 with Sofosbuvir-Ledipasvir, 1 with Sofosbuvir-Ribavirin, 1 with Sofosbuvir-Daclatasvir, 1 with Sofosbuvir-Velpatasvir) and 100% achieved SVR12. In all patients, we observed a trend in reduction of potentially pathogenic microorganisms (i.e., Enterobacteriaceae). Furthermore, a trend of increase in α-diversity was observed in patients by SVR12 compared to baseline. This trend was markedly more evident in patients without liver cirrhosis than in those with cirrhosis. Our study shows that viral eradication obtained with DAA is associated with a trend in restoring the heterogeneity of α-diversity and in reducing the percentage of potentially pathogenic microbial species, although this benefit is less evident in patients with cirrhosis. Further studies with larger sample size are needed to confirm these data.

T he administration of monoclonal antibodies against SARS-CoV-2 reduce the risk of COVID-19–related hospitalization and death. 1 Solid organ transplant (SOT) patients with SARS-CoV-2 infection have higher rates of severe disease progression compared with the general pop-ulation. The availability of such treatments could represent a key therapeutic tool in the fight against COVID-19 and its sequelae. Nevertheless, real world data regarding the use of monoclonal antibodies in these patients are scarce 2 and are limited to few case series based on Casirivimab/ Imdevimab or Bamlanivimab/Etesevimab administration. 3,4 No published study evaluated efficacy and safety of Sotrovimab in this setting so far. We present a small case series of SOT recipients diag-nosed with SARS-CoV-2 infection (positive SARS-CoV-2 RNA detection by RT-PCR on rhino-oropharyngeal swab) treated with sotrovimab (single 500 mg IV dose) at the Division of Infectious Diseases of Federico II University Hospital of Naples, Italy, between December 15, 2021, and January 15, 2022.