Limited data are available on risks and benefits of anti‐SARS‐CoV2 vaccination in solid organ transplant recipients, and weaker responses have been described. At the Italian National Institute for Infectious Diseases, 61 liver transplant recipients underwent testing to describe the dynamics of humoral and cell‐mediated immune response after two doses of anti‐SARS‐CoV2 mRNA vaccines and compared with 51 healthy controls. Humoral response was measured by quantifying both anti‐spike and neutralizing antibodies; cell‐mediated response was measured by PBMC proliferation assay with IFN‐γ and IL‐2 production. Liver transplant recipients showed lower response rates compared with controls in both humoral and cellular arms; shorter time since transplantation and multi‐drug immunosuppressive regimen containing mycophenolate mofetil were predictive of reduced response to vaccination. Specific antibody and cytokine production, though reduced, were highly correlated in transplant recipients.

Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy. Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

Liver injury in COVID-19 patients has progressively emerged, even in those without a history of liver disease, yet the mechanism of liver pathogenicity is still controversial. COVID-19 is frequently associated with increased serum ferritin levels, and hyperferritinemia was shown to correlate with illness severity. The liver is the major site for iron storage, and conditions of iron overload have been established to have a pathogenic role in development of liver diseases. We presented here six patients who developed severe COVID-19, with biochemical evidence of liver failure. Three cases were survived patients, who underwent liver biopsy; the other three were deceased patients, who were autopsied. None of the patients suffered underlying liver pathologies. Histopathological and ultrastructural analyses were performed. The most striking finding we demonstrated in all patients was iron accumulation into hepatocytes, associated with degenerative changes. Abundant ferritin particles were found enclosed in siderosomes, and large aggregates of hemosiderin were found, often in close contact with damaged mitochondria. Iron-caused oxidative stress may be responsible for mitochondria metabolic dysfunction. In agreement with this, association between mitochondria and lipid droplets was also found. Overall, our data suggest that hepatic iron overload could be the pathogenic trigger of liver injury associated to COVID-19.

Background: COVID‑19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator‑associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). Methods: Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. Results: Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5–13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26–3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12–3.84, p = 0.02). The pronation and PaO₂/FiO₂ ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. Conclusions: COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.

The risk of hepatitis C virus (HCV) recurrence after direct-acting antiviral (DAA) treatment is <0.5%. However, the distinction between HCV RNA late relapse and reinfection still represents a challenge in virological diagnostics. The aim of this study was to employ next-generation sequencing (NGS) to investigate HCV RNA recurrence in patients achieving a sustained virologic response (SVR) at least six months post-treatment. NGS was performed on plasma samples from six HCV-positive patients (Pt1–6) treated with DAA. NGS of HCV NS5B was analyzed before treatment (T0), after HCV RNA rebound (T1), and, for Pt3, after a second rebound (T2). Reinfection was confirmed for Pt5, and for the first rebound observed in Pt3. Conversely, viral relapse was observed when comparing T0 and T1 for Pt6 and T1 and T2 for Pt3. Z-scores were calculated and used to predict whether HCV-positive patient samples at different time points belonged to the same quasispecies population. A low Z-score of <2.58 confirmed that viral quasispecies detected at T0 and T1 were closely related for both Pt1 and Pt2, while the Z-score for Pt4 was suggestive of possible reinfection. NGS data analyses indicate that the Z-score may be a useful parameter for distinguishing late relapse from reinfection.

Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8–98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52–4835 U/L); aspartate aminotransferase (AST), 659 (range 64–6588 U/L); and total bilirubin, 3.49 (range 0.4–33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680–895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype.