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Background: People in prison are at high risk of hepatitis C virus (HCV) infection and often have a history of injection drug use and mental health disorders. Simple test-and-treat regimens which require minimal monitoring are critical. Methods: This integrated real-world analysis evaluated the effectiveness of once daily sofosbuvir/velpatasvir (SOF/VEL) in 20 prison cohorts across Europe and Canada. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with a valid SVR status. Secondary outcomes were reasons for not achieving SVR, adherence and time between HCV RNA diagnosis and SOF/VEL treatment. Results: Overall, 526 people in prison were included with 98.9% SVR achieved in the EP (n = 442). Cure rates were not compromised by drug use or existence of mental health disorders. Conclusion: SOF/VEL for 12 weeks is highly successful in prison settings and enables the implementation of a simple treatment algorithm in line with guideline recommendations and test-and-treat strategies.

The efficacy on the Omicron variant of the approved early coronavirus disease-2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. We assessed potential decrease from Day 1 to Day 7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect by weighted marginal linear regression models. A total of 521 patients (378 BA.1 [73%], 143 [27%] BA.2) received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day 1 mean VL was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except versus Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission.

It is not yet entirely clear what is the relevance of skin symptoms and what clinical implications are related to their appearance in COVID‐19 patients. We describe two cases of COVID‐19‐associated pneumonia, which presented skin manifestations in advanced stage of illness, when nasopharyngeal swabs became negative for SARS‐CoV‐2. The first case presented erythematous, maculopapular lesions; the second developed petechial, vesicular and blood‐encrusted lesions on the limbs. Histopathology documented perivascular lymphocytic infiltrates, with prevalent CD4+ T‐cells in both patients. The research of SARS‐CoV‐2 in tissues with real time RT‐PCR was negative. Basal keratinocytes displayed C4d deposits in one case, who developed laboratory signs indicative of a procoagulative condition at the same time as the skin rash. Skin manifestations during SARS‐CoV‐2 infection seem to be clinically relevant and further studies are necessary to assess if they are linked to systemic complications, lack of viral clearance or cascades of immune responses induced by the virus, even in patients affected by mild pneumonia.

ObjectivesComparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta.MethodsAllocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7.Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period.ResultsCOVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% −1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharingeal swab (p=0.009) and 82.4% showed still high viral load (pConclusionsIn a pre-Omicron epidemiologic scenario, CAS/IMD reduced risk of clinical progression of COVID-19 compared to BAM/ETE. This effect was not associated with a concomitant difference in virological response.

SARS-CoV-2 has evolved, leading to the emergence of new Variants Of Concern (VOCs) with significant impact on transmissibility. Although the transmission process is complex, higher nasopharyngeal viral load (NP-VL) can be considered as a proxy for greater transmissibility.The aim of this analysis was to compare NP-VL across a set of representative VOCs observed in mildly symptomatic patients.Observational single-center comparative analysis of patients with early mild-to-moderate COVID-19, enrolled within the early treatment access program of Lazzaro Spallanzani Institute (March 2021-March 2022). NP-VL before drug administration was estimated through RT-PCR, based on cycle threshold values (CTs); VOCs were identified by Sanger sequencing. VOCs' average treatment effect (ATE) was estimated on the CTs fitted in the log2 scale, controlling for potential confounders.A total of 707 patients were included. VOCs were: 10% Alpha, 3% Gamma, 34% Delta, 34% BA.1, 19% BA.2. Mean CTs for BA.1 and BA.2 were lower than Delta and BA.1, respectively. After adjusting for calendar time, age, immunodeficiency and vaccination, CTs for Gamma were lower than those seen for Alpha and higher than Delta, for Delta were similar to BA.1, for BA.2 were lower than Delta and BA.1.Our analysis shows higher NP-VL of BA.2 compared to previously circulating VOCs, even after controlling for factors potentially contributing to the amount of nasopharyngeal viral RNA, included vaccination, supporting the increased transmissibility of BA.2. Further studies are necessary to clarify this mechanism and to provide guidance for public health measures.

Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful microorganisms, including viruses such as Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2). The US Food and Drug Administration (FDA) and the European Medical Agency (EMA) have already authorized monoclonal antibodies of anti-SARS-CoV-2 to treat mild to moderate CoronaVIrus Disease-2019 (COVID-19) in patients at risk of developing severe disease. More recently, monoclonal antibodies anti-SARS-CoV-2 have been authorized for primary and secondary prophylaxis in patients at high risk of severe disease for background comorbidity. Primary or pre-exposure prophylaxis prevents COVID-19 in unexposed people, whereas secondary or postexposure prophylaxis prevent COVID-19 in recently exposed people to individuals with laboratory-confirmed SARS-CoV-2. This review focuses briefly on therapeutic indications of currently available monoclonal antibodies for COVID-19 pre- and postexposure prophylaxis and on the efficacy of convalescent plasma.

Reduced circulation of hepatitis A virus lead to an increase of susceptible individuals, and outbreaks occurred recently. In Northern Italy an outbreak is ongoing, attributed to a monophyletic genotype IA strain, with mixed frozen berries as probable source. From 01/01/2013 to 07/15/2013, 30 cases were diagnosed at National Institute for Infectious Diseases, Rome, Italy, representing about twice the number of cases in whole 2012. Phylogenetic analysis indicated that most, although not all, infections were attributable to the same monophyletic genotype IA strain identified in the contemporary Northern Italy outbreak. This strain is also very similar to previous isolates from Venezuela.

Background The prevalence of chronic hepatitis C virus (HCV) infection in the Italian correctional population is estimated to be around 38%. In this setting HCV infection treatment is controversial because of several factors such as active drug substance abuse, psychiatric illness, length of treatment, risk of re-infection, poor adherence and low success rate. Methods A retrospective data review of 159 inmates, positive for anti-Hepatitis C virus (HCV) antibody, evaluated to National Institute for Infectious Diseases “L. Spallanzani” (INMI) from January 2006 to December 2009, was conducted to evaluate rate of completion (feasibility) and outcome efficacy of chronic Hepatitis C Virus (HCV) infection treatment with Pegylated Interferon and Ribavirin in five correctional facilities in Rome. Results Of the 159 inmates evaluated in the study period, 50, all male (median age 39 years) were treated. Twenty patients (40%) did not complete treatment: 15 showed no response and therapy was stopped, 5 patients (10%) interrupted treatment because of adverse reactions. The global feasibility was 60%. The overall sustained virologic response (SVR) was 50% (32% for genotype 1 and 68% for genotype other than 1). The main predictors of SVR at the Multivariable Logistic Regression Odds Ratio (MLR-OR) were a better pretreatment histological diagnosis (absence of bridging fibrosis or cirrhosis [MLR-OR 11.85; 95% CI 1.96-71.62) and a HCV genotype other than 1 (MLR-OR 5.87; 95% CI 1.49-23.17). Conclusions Chronic HCV infection treatment in correctional facilities is feasible and effective and should be strongly recommended, in combination with preventive measures, in appropriately screened patients because it represents an important opportunity to treat a population with a high prevalence of chronic HCV infection among whom treatment options post incarceration may be limited.

Anti-tumor necrosis factor alpha (anti-TNF-α) is used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure that occurred after etanercept initiation and influenza vaccination in an HIV-infected woman with rheumatoid arthritis.

The aim of this work was to study the distribution of imidacloprid in soil and its translocation to roots and aerial parts of maize plant. The main objective was to assess imidacloprid residues in field environment, in order to provide data on honeybees exposure level to such an active substance. Imidacloprid has been detected and quantified by Triple Quadrupole HPLC-MS-MS. Pesticide persistence in the soil and its residues in pollen and in maize plants have been evaluated during the growing of maize plants developed from seeds dressed with Gaucho 350 FS (imidacloprid: 1.0 mg/seed). The sowing has been performed by means of a pneumatic precision drill. Samples have been collected at 30, 45, 60, 80, 130 days after the sowing, as pollen samples have been collected at the tasseling. Imidacloprid presence in aerial part of maize plant declined to 2-3 μg/kg 80 days after the sowing, while concentration in kernel at harvest was1 μg/kg. Maize pollen represents an important part of protein supply of beehives, and it is of critical importance to bee foraging. The values detected (imidacloprid residues1 μg/kg) showed that maize pollen source should not be relevant for acute toxicity impact on honey bees.

To evaluate the diagnostic value of thallium-201 single-photon emission computed tomography (201Tl SPECT) in the management of focal brain disorders in the era of highly active antiretroviral therapy (HAART), a validation study of diagnostic procedure was performed in a tertiary clinical care center in Italy. Thirty-eight consecutive HIV-infected patients with neurological impairment and focal brain lesions (FBL) were enrolled in a prospective evaluation and underwent diagnostic procedures according to a standardized protocol based on modified previously released guidelines. Six out of seven PCNSL presented high uptake at 201Tl SPECT [sensitivity 86% (95% CI 42-99); specificity 77% (95% CI 58-90); positive predictive value (PPV) 46% (95% CI 20-74); negative predictive value (NPV) 96% (95% CI 78-100)]. Among toxoplasmic encephalitis (TE) cases 14 showed no uptake and 5 showed an increased uptake [sensitivity 74% (95% CI 49-90); specificity 42% (95% CI 21-66); PPV 56% (95% CI 35-75); NPV 61% (95% CI 32-85)]. Patients taking HAART were more likely to display an increased uptake of 201Tl in the cerebral lesions than patients without HAART (OR 5.07; 95% CI 1.19-21.5). Considering only the patients with diagnosis of TE, 60% of patients who showed high radionuclide uptake were taking HAART, while 79% of patients without relevant uptake were not taking HAART. As a result of the impact of HAART, the diagnostic value of 201Tl SPECT in the management of HIV-associated FBL could be substantially reduced. This observation suggests that in HAART-treated patients, this diagnostic tool be used only when combined with other more specific diagnostic markers.

Intra-hepatic levels of mRNA for IFN-a, IFN-y, IFN type 1 receptor (IFNAR-1) and PKR were determined in hepatitis C virus (HCV)/HIV co-infected and HCV mono-infected patients. In co-infected patients, IFN-a mRNA was upregulated and correlated with HIV-1 viraemia. IFN-y, IF-NAR-1 and PKR mRNA were detected in mono-infected, but not in co-infected patients. These findings suggest that in HCV/HIV co-infected individuals the ability to respond to IFN-a is impaired, probably because of the absence of its receptor.