Search

Abstract Background Several scores aimed at predicting COVID-19 progression have been proposed. As the variables vaccination and early SARS-CoV-2 treatment were systematically excluded from the prognostic scores, the present study's objective was to develop a new model adapted to the current epidemiological scenario. Methods We included all patients evaluated by the Infectious Disease Unit in Sassari, with SARS-CoV-2 infection and without signs of respiratory failure at the first evaluation (P/F > 300). Disease progression was defined by the prescription of supplemental oxygen. In addition, variables related to demographics, vaccines, comorbidities, symptoms, CT scans, blood tests, and therapies were collected. Multivariate logistic regression modelling was performed to determine factors associated with progression; any variable with significant univariate test or clinical relevance was selected as a candidate for multivariate analysis. Hosmer–Lemeshow (HL) goodness of fit statistic was calculated. Odds ratio values were used to derive an integer score for developing an easy-to-use progression risk score. The discrimination performance of the risk index was determined using the AUC, and the best cut-off point, according to the Youden index, sensitivity, specificity, predictive value, and likelihood ratio, was chosen. Results 1145 patients [median (IQR) age 74 (62–83) years; 53.5% males] were enrolled; 336 (29.3%) had disease progression. Patients with a clinical progression were older and showed more comorbidities; furthermore, they were less vaccinated and exposed to preventive therapy. In the multivariate logistic regression analysis, age ≥ 60 years, COPD, dementia, haematological tumours, heart failure, exposure to no or one vaccine dose, fever, dyspnoea, GGO, consolidation, ferritin, De Ritis ≥ 1.2, LDH, and no exposure to early anti-SARS-CoV-2 treatment were associated with disease progression. The final risk score ranged from 0 to 45. The ROC curve analysis showed an AUC of 0.92 (95% CI 0.90–0.93) with a 93.7% specificity and 72.9% sensitivity. Low risk was defined when the cut-off value was less than 23. Three risk levels were identified: low (0–23 points), medium (24–35), and high (≥ 36). Conclusions The proportion of patients with progression increases with high scores: the assessment of the risk could be helpful for clinicians to plan appropriate therapeutic strategies.

Abstract Long COVID, also known as “post-acute sequelae of COVID-19,” affects at least 65 million individuals worldwide with a wide spectrum of symptoms that may last weeks, months, or permanently. Its epidemiology and burden in Africa are unclear. This meta-analysis examines long-term COVID-19 effects in the WHO African Region. A systematic search in several databases was carried out up to 12 February 2023 including observational studies from African countries reporting the cumulative incidence of long COVID signs and symptoms. Only studies conducted in African countries were included. Several sensitivity and meta-regression analyses were performed. Among 1547 papers initially screened, 25 were included, consisting of 29,213 participants. The incidence of any long COVID symptomatology was 48.6% (95% CI 37.4–59.8) as psychiatric conditions were the most frequent, particularly post-traumatic stress disorder reaching a cumulative incidence of 25% (95% CI 21.1–30.4). Higher age (p = 0.027) and hospitalization (p = 0.05) were associated with a higher frequency of long COVID. Long COVID poses a significant burden in Africa, particularly concerning psychiatric conditions. The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients. High-quality studies addressing this condition in African setting are urgently needed.

In 2014, UNAIDS launched renewed global targets for HIV control to achieve by 2025, known as “the three 95”: 95% of people living with HIV (PWH) diagnosed, of which 95% are receiving treatment, of which 95% are on sustained virological suppression. In Italy, new HIV diagnoses have been steadily decreasing since 2012. However, in 2020, 41% of new diagnoses presented with less than 200 CD4+ cells/µL and 60% with less than 350 CD4+ cells/µL. Implementing testing and early treatment is a key strategy to prevent AIDS, late presentation, and HIV transmission. We selected non-Infectious Diseases Units based on the European project HIDES and engaged colleagues in a condition-guided HIV screening strategy. We enrolled 300 patients, of which 202 were males (67.3%) and 98 were females (32.7%). Most of the screening was performed in Infectious Diseases (ID) and Hematologic wards. In total, we diagnosed eleven new HIV infections with a hospital prevalence in the study population of 3.7%. Five (45.4%) had a CD4 count 3, one (9.1%) 3, and one (9.1%) 3. Regarding risk factors, 81.8% declared having had unprotected sexual intercourse and 54.5% were heterosexual. All patients promptly started a combination antiretroviral regimen and 10 (90.9%) obtained an undetectable HIV-RNA status. Eight of the eleven (72.7%) patients are currently on follow-up in our outpatient clinic. A proactive indicator disease-guided screening can help avoid missed opportunities to diagnose HIV infection in a hospital setting. Implementing this kind of intervention could favor early diagnosis and access to treatment.

Abstract Background Hepatitis C virus (HCV) infection is more frequent among incarcerated people than in general population. In the DAAs era, the short schedules and the low risk of adverse reactions, increased the number of HCV treatments. However, the most part of literature reports lack of incarcerated women inclusion in studies on field. Our aim is to assess the screening execution, HCV prevalence, and DAAs treatment among incarcerated women. A focused insight on quick vs standard diagnosis and staging approach will be also provided. Methods Incarcerated women from 4 Italian regions’ penitentiary institutes were included. HCV screening was executed with HCV saliva test (QuickOral Test®) or phlebotomy. Stage of liver fibrosis was evaluated with FIB-4 value or fibroscan®, based on physicians’ decision. Treatment prescription followed national protocols. Results We included 156 women, 89 (57%) were Italian, mean age was 41 ± 10 years, and 28 (17.9%) were people who inject drugs (PWIDs). Overall, the HCV seroprevalence was 20.5%. Being PWID and on opioid substitution therapy (OST) were significantly associated with serological status (p-value

Abstract The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including

Abstract Background Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown. Methods A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0–F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic). Results By January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54–0.82%), of which 300,171 (0.50%; 95% CI: 0.4–0.6%) were stage F0–F3. Considering all individuals with HCV in stage F0–F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0–F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36–0.55%), Central 24.1% (0.61%; 95% CI: 0.48–0.74%), South 23.2% (0.50%; 95% CI: 0.4–0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39–0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0–F3). Undiagnosed individuals (F0–F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0–F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values. Conclusion This targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.

Background: Women represent less than 5% of the incarcerated population in Italy, with very limited data on HCV infection. Higher HCV seroprevalence and active infection rates have been described among incarcerated females in available studies. Our aim is to compare the prevalence and cascade of care of HCV between male and female populations in Italian penitentiaries. Methods: We conducted a multicentre, retrospective study comparing HCV seroprevalence, active infections, treatment, and SVR rates between female (Group A) and male (Group B) populations in Italian prison settings. Results: No significant differences were found between the two groups regarding PWIDs (p = 0.16), nor in people living with HIV (p = 0.35) or HBV co-infection (p = 0.36). HCV seroprevalence was higher in Group A (p = 0.002). There was no statistically significant difference between the two groups regarding active infections (p = 0.41). Both groups showed a low level of fibrosis, and the dominant genotype was 3a. Almost all patients underwent antiviral treatment. All treated patients achieved SVR12. Conclusions: Our findings illuminate the importance of recognizing and addressing gender differences in HCV seroprevalence within penitentiary settings. Moving forward, addressing the unique needs of incarcerated females and optimizing HCV care for all incarcerated individuals are essential steps in the pursuit of achieving HCV micro-elimination goals.

Clinical trials demonstrated the role of vaccines and antiviral treatments against SARS-CoV-2 in reducing the likelihood of disease progression and death. However, there are limited data available regarding the time to negativity of people who received these treatments. Further, several comorbidities and risk factors might affect the impact of vaccines and antiviral treatments. To this end, we aimed to evaluate and disentangle the impact of anti-SARS-CoV-2 treatments and that of underlying clinical factors associated with a shortened length of SARS-CoV-2 infection. Hence, we recorded the timeframe of positive nasopharyngeal swab in people infected while being hospitalized for reasons other than SARS-CoV-2 infection. All patients who died or were discharged with a positive swab were excluded from the study. A total of 175 patients were included in this study. Clinical conditions encompass malignancies, immunological disorders, cardiovascular, metabolic, neurodegenerative, and chronic kidney disease. Most of the participants (91.4%) were vaccinated before admission to the hospital, and 65.1% received antiviral treatment within three days after the symptom’s onset. Unvaccinated patients had a longer median time to negativity than people who received at least two doses of vaccine (18 vs. 10 days). Concerning the clinical conditions of all patients, multivariate analysis highlighted a lower probability of 14-day conversion of antigenic test positivity in patients with hematological malignancy, including those vaccinated and those exposed to antiviral therapies. In conclusion, our data showed that prompt administration of antiviral treatments accelerates the clearance of SARS-CoV-2. Further, in the elderly patients under study, previous vaccination and antiviral treatment synergize to reduce time to negativity. This translates into a shorter hospitalization time and a lower risk of transmission through patients and connected healthcare workers in a hospital ward setting, with considerable improvement in cost-effective care management.

(1) Introduction: Since May 2021, sotrovimab has been available in Italy for early treatment of SARS-CoV-2 infection and to prevent disease progression. However, some in vitro studies have questioned its efficacy on Omicron variants. Therefore, we aim to further investigate the efficacy of sotrovimab in real-life settings. (2) Methods: We conducted a retrospective study collecting medical records of people with SARS-CoV-2 infection evaluated in the infectious diseases units of Sassari, Foggia, and Bari, Italy. We included people with SARS-CoV-2 infection treated with sotrovimab and people who did not receive any treatment in 2022. The primary study outcome was to evaluate the efficacy of sotrovimab in reducing disease progression (defined as the necessity of starting oxygen supplementation) and COVID-19-related death. The secondary outcome was to evaluate the safety of sotrovimab. (3) Results: We included 689 people; of them, 341 were treated with sotrovimab, while 348 did not receive any treatment. Overall, we registered 161 (23.4%) disease progressions and 65 (9.4%) deaths, with a significant difference between treated and not-treated people (p < 0.001). In the multivariate logistic regression, increasing age [OR for ten years increasing age 1.23 (95%CI 1.04–1.45)] was associated with a higher risk of disease progression. In addition, cardiovascular disease [OR 1.69 (1.01–2.80), fever [OR 3.88 (95%CI 2.35–6.38)], and dyspnea [OR 7.24 (95%CI 4.17–12.58)] were associated with an increased risk of disease progression. In contrast, vaccination [OR 0.21 (95%CI 0.12–0.37)] and sotrovimab administration [OR 0.05 (95%CI 0.02–0.11)] were associated with a lower risk of developing severe COVID-19. Regarding mortality, people with older age [OR for ten years increasing age 1.36 (95%CI 1.09–1.69)] had a higher risk of death. In addition, in the multivariate analysis, cardiovascular disease lost statistical significance, while people on chemotherapy for haematological cancer [OR 4.07 (95%CI 1.45–11.4)] and those with dyspnea at diagnosis [OR 3.63 (95%CI 2.02–6.50)] had an increased risk of death. In contrast, vaccination [OR 0.37 (95%CI 0.20–0.68)] and sotrovimab treatment [OR 0.16 (95%CI 0.06–0.42)] were associated with lower risk. Only two adverse events were reported; one person complained of diarrhoea a few hours after sotrovimab administration, and one had an allergic reaction with cutaneous rash and itching. (4) Conclusions: Our study showed that sotrovimab treatment was associated with a reduction of the risk of disease progression and death in SARS-CoV-2-infected people, 70% of whom were over 65 years and a with high vaccination rate, with excellent safety. Therefore, our results reinforce the evidence about the efficacy and safety of sotrovimab during the Omicron era in a real-world setting.

Introduction: Spinal Tuberculosis (STB) represents between 1% and 2% of total tuberculosis cases. STB management remains challenging; the first-line approach consists of medical treatment, while surgery is reserved for patients with complications. No data regarding STB treatment with bedaquiline-containing regimens are available in the literature. Case description: Herein, we report the case of a 21-year-old man from Côte d'Ivoire with a multidrug resistance STB with subcutaneous abscess. After approval of the hospital off-label drug committee, we started bedaquiline 400 mg daily for two weeks, followed by 200 mg three times per week, for 22 weeks, associated with linezolid 600 mg daily, rifabutin 450 mg daily, and amikacin 750 mg daily (interrupted after eight weeks). During treatment, we performed a weekly EKG. No QT prolongation was shown, but inverted T waves appeared, requiring several cardiological consultations and cardiac MRI, but no cardiac dysfunction was found. After 24 weeks, bedaquiline was replaced with moxifloxacin 400 mg daily. The patient continued treatment for another year. We performed another computer tomography at the end of treatment, confirming the cure. Discussion: A salvage regimen containing bedaquiline proved effective in treating multidrug-resistance tuberculosis spinal infection without causing severe adverse effects. However, further studies are needed to evaluate better bedaquiline bone penetration and the correct duration of treatment with bedaquiline in MDR spinal tuberculosis.

Background/Aims: Patients with genotype 3 hepatitis C virus (G3-HCV) cirrhosis are very difficult to treat compared to patients with other HCV genotypes. The optimal treatment duration and drug regimen associated with ribavirin (RBV) remain unclear. To evaluate the efficacy and safety of daclatasvir (DCV)/sofosbuvir (SOF) plus a flat dose of 800 mg RBV (flat dose) compared to DCV/SOF without RBV or DCV/SOF plus an RBV dose based on body weight (weight-based) in G3-HCV patients with compensated or decompensated cirrhosis. Methods: We analyzed data for 233 G3 cirrhotic patients. Of these, 70 (30%), 87(37%) and 76 (33%) received SOF/DCV, SOF/DCV/RBV flat dose, and SOF/DCV/RBV weight-based dose, respectively. Treatment duration was 24 weeks. Sustained virological response (SVR) was evaluated at week 12 posttreatment (SVR12). Results: Overall, SVR12 was achieved in 220 out of 233 patients (94.4%). The SVR12 rate was lower in the DCV/SOF group than in the DCV/SOF/RBV flat-dose group and the DCV/SOF/RBV weight-based group (87.1% vs 97.7% and 97.4%, respectively, p=0.007). A higher incidence of anemia occurred in the DCV/SOF/RBV weight-based group compared to those in the other two groups (p

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.

After 40 years of its appearance, human immunodeficiency virus (HIV) infection remains a leading public health challenge worldwide. Since the introduction of antiretroviral treatment (ART), HIV infection has become a chronic condition, and people living with HIV could have life expectancies close to those of the general population. People with HIV often have an increased risk of infection or experience more severe morbidity following exposure to vaccine-preventable diseases. Nowadays, several vaccines are available against bacteria and viruses. However, national and international vaccination guidelines for people with HIV are heterogeneous, and not every vaccine is included. For these reasons, we aimed to perform a narrative review about the vaccinations available for adults living with HIV, reporting the most updated studies performed for each vaccine among this population. We performed a comprehensive literature search through electronic databases (Pubmed—MEDLINE and Embase) and search engines (Google Scholar). We included English peer-reviewed publications (articles and reviews) on HIV and vaccination. Despite widespread use and guideline recommendations, few vaccine trials have been conducted in people with HIV. In addition, not all vaccines are recommended for people with HIV, especially for those with low CD4 cells count. Clinicians should carefully collect the history of vaccinations and patients’ acceptance and preferences and regularly check the presence of antibodies for vaccine-preventable pathogens.

IntroductionSARS-CoV-2 is fundamentally a respiratory pathogen with a wide spectrum of symptoms. The COVID-19 related pancreatitis is less considered than other clinical features. The purpose is to describe two cases of pancreatitis associated with COVID-19.MethodologyPatients' demographics, clinical features, laboratory, and instrumental findings were collected.ResultsTwo patients admitted to the hospital were diagnosed with COVID-19 and severe acute pancreatitis, according to the Atlanta criteria. Other causes of acute pancreatitis were excluded. Treatment included broad-spectrum antibiotics, proton pump inhibitors, and low molecular weight heparin. Steroids, oxygen, antifungal treatment, and pain killers were administered when appropriate. Both patients were asymptomatic, with normal vital parameters and blood exams, and were discharged in a good condition.ConclusionIt is recommendable to include lipase and amylase on laboratory routine tests in order to evaluate the need for the abdominal CT-scan and specific therapy before hospital admission of the patients with COVID-19 related life-threatening acute pancreatitis.

Background: Incarcerated women are a minority in the Italian prison population. The lack of prevention and awareness of HIV infection and the lack of access to treatment make the treatment path difficult. Methods: we conducted a multi-center study including incarcerated women living with HIV (WLWH). Results: The study included 85 WLWH with a mean age of 41.7 ± 8.7 years, and 58.8% (50/85) of them were Italian. Principally, HIV transmission was related to sexual intercourse, 47% of all patients were PWIDs, and 62.5% of them were on opioid substitution therapy (OST). Overall, 56.4% of the included patients had a CD4+ cell count of >500 cells/mmc. Among the participants, 92.9% were on antiretroviral therapy, 87.3% had treatment before incarceration, and 83.5% were virologically suppressed. Among the 13 non-virally-suppressed patients, 53.8% were unaware of their serological status before incarceration and had started HAART but were still not virologically suppressed; 46.2% (6/13) had a lack of compliance or had suspended the treatment before incarceration and restarted it after admission. All patients with chronic hepatitis C underwent treatment with direct-acting antivirals and reached a sustained virological response. Conclusions: the detention of these women could represent an occasion for the patients’ healthcare provision and use, and the creation of a gender-specific network can be an effective strategy for reaching this population.

Undocumented migrant sex-workers (SW) are vulnerable to Sexually Transmitted Infections (STIs). However, data regarding prevalence and linkage-to-care are lacking. Defining epidemiology is crucial to implement preventive measures. We report data from SW attending a facility for migrants in Piacenza, Italy. We collected medical records from 1999 until 2021. Quantitative variables were summarized as mean and standard deviation (SD), and qualitative ones by absolute and relative frequencies. Logistic regression analysis was performed to assess the relationship between sociodemographic, clinical variables, positive testing, and loss to follow-up (LFU). Overall, 1035 STI episodes were collected, 917 in cisgender-females (CF), and 118 in transgender-females (TF). Overall, 474 diagnoses were made. Three-hundred-ninety-two/474 (82.7%) started therapy, and 264/474 (55.7%) complied with a follow-up. Only 51.5% of HBV and 30.8% of HIV were linked to care. Having symptoms (OR 1.70 (95% CI 1.06–2.73), p = 0.028) and previous STIs (OR 1.36 (95% CI 1.04–1.77), p = 0.022) were associated with a higher chance of STIs, while at-risk intercourse to lower risk (OR 0.19 (95% CI 0.07–0.49), p = 0.001). TF had higher odds of bloodborne infections and syphilis (OR 2.61 (95% CI 1.17–5.80), p = 0.019). Regarding follow-up, the older the patient, the higher the LFU (OR 1.05 (95% CI 1.01–1.10), p = 0.021). Our data showed a high prevalence of STIs and LFU among undocumented SW. TF are even more vulnerable. Further efforts should be put into targeted interventions.

Since the start of the SARS-CoV-2 pandemic, several scores have been proposed to identify infected individuals at a higher risk of progression and death. The most famous is the 4C score. However, it was developed in early 2020. Our study aimed to evaluate the accuracy of the 4C score during the wave in which the Omicron variant was prevalent. An observational study was conducted at an Italian University Hospital between 1 January and 31 July 2022. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of the 4C score to predict mortality. Overall, 1186 people were recruited, of which 160 (13.5%) died. According to the 4C score, 177 (11.6%) were classified as having a low risk of mortality, 302 (25.5%) were intermediate, 596 (50.3%) were high, and 151 (12.7%) were very high. The ROC curve of the 4C score showed an AUC (95% CI) value of 0.78 (0.74–0.82). At the criterion value of > 10, the sensitivity was 76.2% and the specificity was 62.67%. Similar to previous studies, the 4C mortality score performed well in our sample, and it is still a useful tool for clinicians to identify patients with a high risk of progression. However, clinicians must be aware that the mortality rate reported in the original studies was higher than that observed in our study.

Since the start of the SARS-CoV-2 pandemic, several treatments have been proposed to prevent the progression of the disease. Currently, three antiviral (molnupiravir, nirmaltrevir/r, remdesivir) and two monoclonal antibodies (casirivimab/imdevimab and sotrovimab) are available in Italy. Therefore, we aimed to evaluate the presence of risk factors associated with disease progression. We conducted a retrospective cohort study, including all patients with a confirmed diagnosis of SARS-CoV-2 evaluated between 01/01/2022 ad 10/05/2022 by our Unit of Infectious Diseases in Sassari. We defined disease progression as the necessity of starting O2 therapy. According to AIFA (Italian Medicines Agency) indications, preventive treatment was prescribed in patients with recent symptoms onset (≤five days), no need for oxygen supplementation, and risk factors for disease progression. Subgroup differences in quantitative variables were evaluated using Student’s t-test. Pearson chi-square or Fisher’s exact tests were used to assess differences for qualitative variables. Multivariate logistic regression modelling was performed to determine factors associated with progression. A two-tailed p-value less than 0.05 was considered statistically significant. All statistical analyses were performed with STATA version 17 (StataCorp, College Station, TX, USA). We included 1145 people with SARS-CoV-2 diagnosis, of which 336 (29.3%) developed severe disease with oxygen supplementation. In multivariate logistic regression analysis, age, dementia, haematologic tumors, heart failure, dyspnoea or fever at first evaluation, having ground glass opacities or consolidation at the first CT scan, and bacteria coinfection were associated with an increased risk of disease progression. Vaccination (at least two doses) and early treatment with antiviral or monoclonal antibodies were associated with a lower risk of disease progression. In conclusion, our study showed that vaccination and early treatment with antiviral and/or monoclonal antibodies significantly reduce the risk of disease progression.

Background: People with psychiatric disorders have a high prevalence of HCV. For this reason, tailored interventions should be developed to reach this population. Methods: We performed a retrospective study on patients treated for HCV infection in psychiatric nursing homes, approached with a quick diagnosis, staging and treatment. Results: We included data on 586 people screened for HCV with quick tests. High HCV seroprevalence was found in this population (231; 39.4%). Among people who tested positive, there were high rates of active infection (220; 95.2%). Out of the 220 patients with active infection, 95.9% were male, 85.5% were Italian, median age was 43 (IQR = 35–52) years old. In the majority of cases (162; 73.6%), the risk factor was unknown. The most common genotype was 3a (98; 44.5%), and patients mostly had a low fibrosis, according with FIB-4 value (142; 64.5%). Of them, one (0.45%) categorically refused the treatment, and one (0.45%) had liver cirrhosis and advanced hepatocellular carcinoma. Overall, 218 patients underwent eligibility for DAAs. The most prescribed treatment was glecaprevir/pibrentasvir (GLE/PIB (172; 78.2%)). The others practiced sofosbuvir/velpatasvir (SOF/VEL). All patients reached the end of treatment. One (0.45%) was lost to follow up, and all the others reached the SVR12. Conclusions: The point-of-care testing and pangenotypic DAAs’ availability represent one of the most important steps for a fast diagnostic and therapeutical option. Tailored microelimination pathways for every difficult-to-reach/to-treat populations are needed. This would allow us to move more easily towards HCV elimination.

Background: The universal treatment of diagnosed patients with chronic HCV infection has been widely conducted in Italy since 2017. However, the pool of individuals diagnosed but yet to be treated in Italy has been estimated to end around 2025, leaving a significant proportion of infected individuals undiagnosed/without care. Estimates of this population are currently unknown. Methods: A probabilistic modelling approach was applied to estimate annual historical HCV incident cases by their age-group (0–100 years) distribution from available literature and Italian National database (1952 to October 2019). Viraemic infection rates were modelled on the main infection routes in Italy: people who inject drugs (PWID), tattoos, sexual transmission, glass syringe use, blood transfusion and vertical transmission. Annual liver fibrosis stage transition probabilities were modelled using a Markov model. The number of HCV viraemic asymptomatic (fibrosis stage F0-F3:potentially undiagnosed/unlinked to care) and symptomatic (fibrosis stage F4: potentially linked to care) individuals was estimated. Results: By October 2019, total viraemic HCV individuals in Italy (excluding treated patients since 1992) were estimated to be 410,775 (0.68 % of current population of Italy; 95 % CI: 0.64−0.71%, based on the current Italian population), of which 281,809 (0.47 %; 95 % CI:0.35−0.60%) were fibrosis stage F0-F3. Among different high risk groups in stage F0-F3, the following distribution was estimated: PWID; 52.0 % (95 % CI:37.9–66.6 %), tattoo; 28.8 % (95 % CI:23–32.3 %), sexual transmission; 12.0 % (95 % CI:9.6–13.7 %), glass syringe and transfusion; 6.4 % (95 % CI:2.4–17.8 %), and vertical transmission; 0.7 % (95 % CI:0.4–1.2 %). Conclusion: Under the assumption that most untreated HCV-infected individuals with stage F0-F3 are undiagnosed, more than 280,000 individuals are undiagnosed and/or unlinked to care in Italy. Marked heterogeneity across the major routes of HCV transmission was estimated. This modelling approach may be a useful tool to characterise the HCV epidemic profile also in other countries, based on country specific epidemiology and HCV main transmission routes.

Several studies evaluated the presence of SARS-CoV-2 in the environment. Saliva and nasopharyngeal droplets can land on objects and surfaces, creating fomites.

IntroductionSince the start of the pandemic, millions of people have been infected, with thousands of deaths. Many foci worldwide have been identified in retirement nursing homes, with a high number of deaths. Our study aims were to evaluate the spread of SARS-CoV-2 in the retirement nursing homes, the predictors to develop symptoms, and death.Methods and findingsWe conducted a retrospective study enrolling all people living in retirement nursing homes (PLRNH), where at least one SARS-CoV-2 infected person was present. Medical and clinical data were collected. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on infection and symptoms development. Cox proportional-hazards model was used to evaluate 30 days mortality predictors, considering death as the dependent variable. We enrolled 382 subjects. The mean age was 81.15±10.97 years, and males were 140(36.7%). At the multivariate analysis, mental disorders, malignancies, and angiotensin II receptor blockers were predictors of SARS-CoV-2 infection while having a neurological syndrome was associated with a lower risk. Only half of the people with SARS-CoV-2 infection developed symptoms. Chronic obstructive pulmonary disease and neurological syndrome were correlated with an increased risk of developing SARS-CoV-2 related symptoms. Fifty-six (21.2%) people with SARS-CoV-2 infection died; of these, 53 died in the first 30 days after the swab's positivity. Significant factors associated with 30-days mortality were male gender, hypokinetic disease, and the presence of fever and dyspnea. Patients' autonomy and early heparin treatment were related to lower mortality risk.ConclusionsWe evidenced factors associated with infection's risk and death in a setting with high mortality such as retirement nursing homes, that should be carefully considered in the management of PLRNH.

The purpose of the present review is to give an update regarding the classification, the epidemiology, the clinical manifestation, the diagnoses, and the treatment of the Rickettsiae species present in the Mediterranean area. We performed a comprehensive search, through electronic databases (Pubmed – MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles, reviews, and books). The availability of new diagnostic tools, including Polymerase Chain Reaction and nucleotide sequencing has significantly modified the classification of intracellular bacteria, including the order Rickettsiales with more and more new Rickettsia species recognized as human pathogens. Furthermore, emerging Rickettsia species have been found in several countries and are often associated with unique clinical pictures that may challenge the physician in the early detection of the diseases. Rickettsial infections include a wide spectrum of clinical presentations ranging from a benign to a potentially life treating disease that requires prompt recognition and proper management. Recently, due to the spread of SARS-CoV-2 infection, the differential diagnosis with COVID-19 is of crucial importance. The correct understanding of the clinical features, diagnostic tools, and proper treatment can assist clinicians in the management of Rickettsioses in the Mediterranean area.

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and β-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.

Background. The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. Methods. The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. Results. Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan–Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000–1.0001, p = 0.029) in multivariate Cox regression analysis. Conclusions. The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.

IgG4-related disease is a fibroinflammatory systemic condition characterized by tumefactive lesions, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and elevated serum IgG4 concentrations. It has been described in virtually every organ system. Autoimmunity and infectious agents are potential immunologic triggers in IgG4-related disease. Herein, we describe a peculiar case of effusive-constrictive pericarditis in an 18-year-old boy with polyserositis and concomitant Necator americanus infection.

Introduction. To evaluate the characteristics of alcohol-related chronic liver disease (CLD) in Italy and their potential changes over time. Patients and Methods. Subjects with CLD were enrolled in two national surveys performed in 2001 and in 2014 in Italy. The two surveys prospectively recruited patients aged ≥ 18 years referring to more than 80 Italian liver units scattered all over the country using similar clinical approach, analytical methods, and threshold of risky alcohol intake definition (≥ 3 units/day in men and ≥ 2 units/day in women). Results. Out of 12,256 enrolled subjects, 2,717 (22.2%) reported a risky alcohol intake. Of them, anti-HCV positive was observed in 48.3% of subjects. The overall sex ratio (M/F) was 3.1, decreasing from 3.8 in 2001 to 1.3 in 2014. Women were significantly older than men (58.9 versus 53.1 years; p

Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR.Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization.HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p

Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs and symptoms in the early stages. This fact, along with the poor results of the local and systemic therapies currently employed, is responsible for the poor outcome of CCA patients and strongly supports the need for novel therapeutic agents and strategies. In recent years, the introduction of next-generation sequencing technologies has opened new horizons for a better understanding of the genetic pathophysiology of CCA and, consequently, for the identification and evaluation of new treatments tailored to the molecular features or alterations progressively elucidated. In this review article, we describe the potential targets under investigation and the current molecular therapies employed in biliary tract cancers. In addition, we summarize the main drugs against CCA under evaluation in ongoing trials and describe the preliminary data coming from these pioneering studies.

MicroRNAs fine-tune the regulation of Th1/Th17 lymphocyte subsets in multiple sclerosis. We investigated the expression of miRNAs (previously associated with mycobacterial and viral infections) in MS patients and healthy donors (HD) following 6 months natalizumab therapy. In addition, Th1/Th17 cytokines and the presence of anti-EBNA1/VCA IgG in MS patients with different pattern of miRNA expression have been evaluated. MiR-155, miR-26a, miR-132, miR-146a and Th1/Th17 cytokines expression was detected by RT-real time PCR; moreover anti-EBNA1 and VCA IgG titres were measured by ELISA. We observed an up-regulation of miR-155 (p value = 0.009) and miR-132 (p value = 0.04) in MS patients compared to HD. In MS patients, IL-17a (p = 0.037), IFN γ (p = 0.012) and TNFα (p = 0.015) but not IL-6 were over-expressed compared to HD. Two different miRNAs patterns associated to the expression of different cytokines were observed in the MS cohort. Moreover, a down-regulation of miR-155 and miR-26a was seen in MS patients during and after natalizumab therapy. MS patients that over-expressed miR-155 showed a higher EBNA1 IgG titer than MS patients with high levels of miR-26a. In conclusions the expression of particular miRNAs modulates the pro-inflammatory cytokine expression and the humoral response against EBV and this expression is natalizumab regulated.

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These novel findings suggest HERV-W/MSRV activation as the missing link between EBV and MS, and may open new avenues of intervention.

Enzyme-based chemical biosensors are based on biological recognition. In order to operate, the enzymes must be available to catalyze a specific biochemical reaction and be stable under the normal operating conditions of the biosensor. Design of biosensors is based on knowledge about the target analyte, as well as the complexity of the matrix in which the analyte has to be quantified. This article reviews the problems resulting from the interaction of enzyme-based amperometric biosensors with complex biological matrices containing the target analyte(s). One of the most challenging disadvantages of amperometric enzyme-based biosensor detection is signal reduction from fouling agents and interference from chemicals present in the sample matrix. This article, therefore, investigates the principles of functioning of enzymatic biosensors, their analytical performance over time and the strategies used to optimize their performance. Moreover, the composition of biological fluids as a function of their interaction with biosensing will be presented.