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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.

Despite the lightning-fast advances in the management of SARS-CoV after 2 years of pandemic, COVID-19 continues to pose a challenge for fragile patients, who could benefit from early administration of monoclonal antibodies (mAbs) to reduce the risk of severe disease progression. We conducted a prospective study to evaluate effectiveness of mAbs against SARS-CoV-2 among patients at risk for severe disease progression, namely elderly and those with comorbidities, before the omicron variant surge. Patients were treated with either casirivimab/imdevimab, sotrovimab, and bamlanivimab/etesevimab. The rates and risk factos for clinical worsening, hospitalization, ICU admission and death (unfavourable outcomes) were evaluated. A stratified analysis according to the presence of SARS-CoV-2 IgG was also performed. Among 185 included patients, we showed low rates of unfavorable outcomes (9.2%), which were more frequent in patients with chronic kidney disease (aOR: 10.44, 95CI: 1.73-63.03; p600 ng/ml (aOR 21.74, 95CI: 1.18-397.70; p

Molnupiravir and Nirmatrelvir are the first available oral antivirals (OA) active against SARS-CoV-2. However, the trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. The purpose of this study is to provide real-life data on the efficacy and safety of OAs during the omicron surge of COVID-19 pandemic in a cohort of mostly vaccinated patients.We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy.We enrolled 257 patients. Of these, 146 (56.8%) were treated with molnupiravir and 111 (43.2%) with nirmatrelvir/ritonavir. Patients in molnupiravir group were older, had a lower body mass index, and a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir.During the 14-day follow-up, four hospitalizations were recorded (1.6%), three in molnupiravir (2.1%) and 1 in nirmatrelvir/ritonavir (0.9%) group. Only one patient (who had received molnupiravir) died. Median time-to-negativity of nasal swab was 8 days (8 days in nirmatrelvir/ritonavir vs. 10 days in molnupiravir group, pGlobally, we recorded 37 adverse drug reactions (mainly dysgeusia, diarrhea, and nausea) in 31 of 257 individuals (12.1%). Only two patients (0.8%), both receiving molnupiravir, terminated treatment due to the development of adverse drug reactions.In conclusion, during the omicron surge, in a population of mostly vaccinated patients treated with molnupiravir or nirmatrelvir/ritonavir, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were even lower than those reported in pivotal trials.

To evaluate safety and efficacy of casirivimab/imdevimab therapy in pregnant women with severe COVID-19 requiring oxygen therapy.This was a prospective case series study aimed to evaluate safety and efficacy of casirivimab/imdevimab therapy in unvaccinated pregnant women with severe COVID-19. Inclusion criteria were: SARS CoV-2 infection documented with PCR, pregnancy, severe COVID-19 requiring oxygen therapy, duration of symptoms of 10 days or less, 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 single intravenous dose of 4000/4000 mg. Women were also treated with low molecular weight heparin, steroids and antibiotics, if necessary. The primary outcome was maternal death. Secondary outcomes were: rate of adverse events during infusion or within 72 hours, and rate of abortion.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 intensive care unit. No abortion or fetal loss were 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.Casirivimab/imdevimab therapy may be considered as therapy in unvaccinated pregnant women with severe COVID-19.

Mother-to-child transmission (MTCT) is mainly responsible for the global pediatric HIV and HBV epidemic. Vertical transmission can be prevented and reduced through a series of interventions at the primary healthcare level, including extensive screening of pregnant women, administration of antivirals or immune-based treatments, counselling on type of delivery and breastfeeding.In this narrative review, approved therapeutic options for the treatment of pregnant women living with HIV or HBV are discussed with special focus on efficacy and safety profiles of each agent or drug class examined. The search was performed using Medline (via PubMed), Web of Science, and Google Scholar to identify studies assessing vertical transmission of both HIV and HBV.Elimination of MTCT of both infections is firmly endorsed by major global commitments and the integration of tailored preventive interventions into maternal and newborn health services is of strategical importance to achieve this critical target. However, further research centered on antiviral-based and immunization trials among pregnant women is urgently needed to mitigate the risk of maternal and neonatal adverse outcomes, effectively prevent transmission to the offspring and finally eliminate the pediatric HIV and HBV epidemic, one of the key global health challenges of our time.

Even several months after the start of a massive vaccination campaign against COVID-19, mortality and hospital admission are still high in many countries. Monoclonal antibodies against SARS-CoV-2 are the ideal complement to vaccination in infected subjects who are at high risk for progression to severe disease. Based on data of the Italian Ministry of Health, in the period April–August 2021, monoclonal antibodies were prescribed to 6322 patients. In the same period, 70,022 patients over 70 years old became infected with SARS-CoV-2. Even considering that all monoclonal antibodies were prescribed to this category of patients, we calculated that only 9% of these subjects received the treatment. Moreover, using efficacy data provided by clinal trials, we estimated the potential benefit in terms of reduction of hospital admissions and deaths. Considering utilisation of monoclonal antibodies in half infected patients over 70 years, we estimated that hospital admissions and deaths might have been reduced by 7666 and 3507, respectively. Finally, we calculated the economic benefit of monoclonal use. In the same scenario (50% use of monoclonal antibodies to patients over 70), we estimated potential savings of USD 117,410,105. In conclusion, monoclonal antibodies were used in a small proportion of patients over 70 in Italy. A more extensive use might have resulted in a marked decrease in hospital admissions, deaths and in conspicuous saving for the health system.

Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines.

Monoclonal antibodies have been a milestone in the treatment of multiple sclerosis (MS). Infective complications have been observed in patients on agents targeting lymphoid cells' surface antigens, namely anti-CD52 (alemtuzumab) and anti-CD20 agents (ocrelizumab and rituximab). Despite increasing emerging data, there is no standardized consensus regarding pre-treatment testing, vaccinations, and patient education before and during MS therapy or optimal infection-control strategies.We led a retrospective/prospective real-life study to evaluate the effectiveness of a program of screening and prophylaxis for infective adverse events in patients with multiple sclerosis and related disorders treated with drugs directed against CD20/52 antigens. All patients referring to the MS Clinical Care and Research Center, University of Naples "Federico II", who started on alemtuzumab, ocrelizumab or rituximab (off-label use) from 1 November 2015 to 30 June 2019 were recruited. From the 1st of February 2018 patients underwent a microbiological screening and were evaluated by an infectious disease specialist (IDs) before monoclonal antibodies infusion to rule out active infections. We evaluated incidence of infective complications and predictors before (retrospectively)and after (prospectively) the introduction of the above-mentioned anti-infective program.We enrolled 275 patients, 104 retrospectively (pre-intervention group, PRE) and 171 prospectively (post-intervention group, POST). In PRE group, most patients were treated with alemtuzumab (58% vs 32%, p 0.001), were more frequently DMT naïve (48% vs 36%, p = 0.044) or had received fingolimod in the past (48% vs 28%, p = 0.044) and the follow-up period was longer than in POST group (750 vs 191 days, p 0.001). In POST group, patients were older (median age 47 vs 42 years, p = 0.030) and mostly received OCR (54% vs 14%, p 0.001). Lymphopenia at baseline was significantly more commonly observed in PRE arm (47% vs 8%, p 0.001). A total of 39 patients (38%) in PRE arm and 42 patients (25% in POST) group experienced one or more infections (p = 0.022); severe infections were significantly more common in PRE patients (23% vs 14%, p = 0.022). Our anti-infective program was associated with a lower IAE incidence both at univariate and multivariate analysis (aHR of infective events in PRE group: 3.652 [CI: 9.03-94.19], p 0.001). Moreover, DMT naïve patients significantly experienced fewer infective complications (aHR: 0.470, [CI: 1.02-2.55], p = 0.040).A risk mitigation program including infectious disease consultation and standardized screening and prophylactic protocols was effective in reducing infective adverse events in patients receiving anti CD20/CD52 agents for MS.

Background Despite vaccinations are scientifically proven to be safe and effective public controversies limit their application in many countries. Aims Aim of this review is to provide an overview of biological effects of vaccination and a picture of the ethical dilemmas about compulsory vaccination. Methods We conducted a review on the literature about the subject. Recent news were also included. Results Vaccines are the best weapon against many infectious diseases. The spread of false beliefs among people have led the government authorities to increase compulsory vaccination in order to embank new outbreaks of preventable infectious diseases. Conclusion Even if compulsory is quite drastic approach it could be the on only way to reach an adequate coverage and protect immunoexpressed subjects.

KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at &gt, 1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6: 1188 U/mL vs. 260 U/mL, p &lt, 0.001). KL-6 &gt, 1000 U/mL resulted independently associated with death (aOR: 11.29, p &lt, 0.05) with a positive predictive value of 83.3%. Our results suggest that KL-6 is a reliable indicator of pulmonary function and unfavourable outcome in patients with COVID-19 pneumonia. A KL-6 value &gt, 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome. KL-6 may thus represent a quick, inexpensive, and sensitive parameter to stratify the risk of severe respiratory failure and death.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Introduction: Liver cirrhosis is a frequent condition caused by different etiologies. Bacterial and fungal infections are common complications, representing an independent prognostic stage in patients with cirrhosis, dramatically worsening their clinical outcomes. Areas covered: The present review article addresses manifold points and to this purpose an inductive literature search of MEDLINE database through PubMed was performed. First, it provides an overview on the mechanisms underlying immune disfunctions in patients with cirrhosis, who are prone to develop infections being at higher risk than the general population. Second, commonest types of bacterial and fungal infections in patients with advanced liver disease are described, focusing on their deleterious impact as decompensating events. Third, the rise of multidrug-resistant (MDR) bacteria and fungi as causative agents of infection in cirrhotic subjects is illustrated. Eventually, the most promising novel therapeutic options against MDR pathogens and fungi are reviewed. Expert opinion: The management of bacterial and fungal infections in patients with cirrhosis is difficult, due to the frequent co-existence of renal impairment, low platelet count and other conditions that limit the antimicrobial choice. New antibacterial and antifungal compounds may overcome this issue by providing a better tolerability profile, along with equal or superior efficacy compared with older drugs.

Summary Objectives Pregnant women represent a category at high risk of severe measles infection, that negatively affects the fetus as well. A systematic review of clinical outcomes of measles infection in gravid subjects and a meta-analysis of antibodies prevalence among pregnant women was conducted. Methods MEDLINE and EMBASE databases were searched up to 18 June 2018. The screening focused on: (i) articles describing the outcome of measles in pregnancy, synthesized in a descriptive fashion; (ii) articles addressing the measles seroprevalence in cohorts of gravid women, analysed quantitatively. Results Twenty-nine articles met inclusion criteria. A total of 420 cases of measles in gravid subjects were described, from 1941 to 2012. Among women, 18 deaths (4.3%) occurred, and the most frequent complication was pneumonia (75/420, 17.9%). Prematurity was the most important complication concerning fetal outcomes (55 out of 410 cases with available data, 13.4%). The random-effects pooled seroprevalence of measles in 20,546 gravid women worldwide was 89.3% (95% CI: 87.3–91.1%), that decreased, although not in a statistically significant way, over time (p = 0.54). Conclusions Measles infection in pregnancy is dangerous both for the mother and the foetus. Antibody seroprevalence among gravid women on a global scale is lower than the herd immunity threshold.

Background: Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies. Methods: We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts. Results: Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials. Conclusion: Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to “unpackage” current DAA combinations and to develop generic drugs against HCV.

Background Despite vaccinations are scientifically proven to be safe and effective public controversies limit their application in many countries. Aims Aim of this review is to provide an overview of biological effects of vaccination and a picture of the ethical dilemmas about compulsory vaccination. Methods We conducted a review on the literature about the subject. Recent news were also included. Results Vaccines are the best weapon against many infectious diseases. The spread of false beliefs among people have led the government authorities to increase compulsory vaccination in order to embank new outbreaks of preventable infectious diseases. Conclusion Even if compulsory is quite drastic approach it could be the on only way to reach an adequate coverage and protect immunoexpressed subjects.

Chickenpox is a highly contagious disease caused by primary infection of varicella zoster virus (VZV). The disease is spread worldwide and is usually benign but, in some groups of population like pregnant women, can have a severe outcome. Due to a not optimal vaccination coverage, a relatively high number of childbearing-aged women in a European country such as Italy tested seronegative for VZV and so are currently at risk of acquiring chickenpox during pregnancy, especially if they live in contact with children for family or work reasons. Only few data are available about the risk of infection in this setting: the incidence of chickenpox may range from 1.5 to 4.6 cases/1000 childbearing females and from 1.21 to 6 cases/10,000 pregnant women, respectively. This review is aimed to focus on the epidemiology and the clinical management of exposure to chickenpox during pregnancy. Particular emphasis is given to the accurate screening of childbearing women at the time of the first gynecological approach - the females who tested susceptible to infection can be counseled about the risks and instructed on procedure should contact occur - and to the early prophylaxis of the at-risk exposure. Lastly, the achievement of adequate vaccination coverage of the Italian population remains a cornerstone in the prevention of chickenpox in pregnancy.