INTRODUCTION:Hepatitis B virus (HBV) genotype E, mainly found in sub-Saharan Africa, exhibits low genetic diversity, unique molecular markers and high recombination potential but remains under-studied. AIM:This study describes the clinical and virological characteristics, mutational profiles, antiviral treatment responses and phylogenetic data of patients with confirmed HBV genotype E infection in a tertiary-care centre in northern Italy. METHODS:A retrospective monocentric study was conducted at ASST Spedali Civili di Brescia, Italy, from 2015 to 2023. Patients with documented HBV genotype E who underwent genotypic resistance testing (GRT) for clinical reasons were included. Direct sequencing of the S/POL region was used for genotyping and mutation analysis, interpreted via Geno2pheno [hbv] 2.0 and Stanford HBV resistance tools. RESULTS:Eight patients were identified, mostly male (62.5%) and of African origin (87.5%), with a median age of 38.5 years. GRT was performed in six (75%) patients because of persistent viremia despite antiviral treatment, five (83.3%) of whom were HIV/HBV coinfected with detectable HIV viral load. Lamivudine resistance mutations (L180M, M204V) were found in one (12.5%) case, tenofovir resistance-associated mutations (M267L/I) in two (25%) and immune escape mutations in three (37.5%), including T126I, D144E and G145R. Despite GRT, treatment was not modified in four (50%) patients due to poor adherence concerns. Therapy adjustments led to viral suppression in three (37.5%) cases. CONCLUSION:In our setting, HBV genotype E infections largely occurred among migrants from endemic regions. Although nucleos(t)ide analogues are effective across genotypes, suboptimal adherence may hinder viral suppression and promote resistance.
BACKGROUND:The COVID-19 pandemic demonstrated the need for a larger pallet of antivirals. Ideally cheap, safe, widely available, easy to administer and resistant to virus mutation. Statins meet these criteria and repurposing statins, which inhibit cholesterol synthesis, is appealing since enveloped viruses need to cross the cholesterol-rich plasma membrane both upon cell infection and egress of new virus particles. OBJECTIVES:To investigate whether, when and how simvastatin has antiviral effects against SARS-CoV-2 infection and how simvastatin treatment affects the organisation of the plasma membrane. METHODS:Calu-3 and Vero cells were infected with the D614G and BA.1 SARS-CoV-2 virus strains. Infection, binding and internalisation was assessed using RT-qPCR. Membrane order was assessed by live cell fluorescence microscopy and ACE2 distribution by immunofluorescence. RESULTS:Simvastatin reduces SARS-CoV-2 infection in Calu-3 and Vero cells in a dose-dependent manner at clinically relevant concentrations in a virus strain independent manner. Importantly, simvastatin pre-treatment was necessary for the antiviral effect. Simvastatin treatment reduced the membrane order, i.e. the lipid packing, of the plasma membrane and resulted in a higher intracellular presence of ACE2. The membrane organisation changes neither affected virus binding at 4 °C nor internalisation of the pre-bound virus particles. CONCLUSIONS:Pre-treatment is essential for the antiviral effect of simvastatin and is accompanied by a rearrangement of the plasma membrane with reduced lipid packing and altered ACE2 distribution. Our results suggest that simvastatin could be effective when taken prophylactically and may be effective when used early in the course of COVID-19 disease.
BACKGROUND:Respiratory Syncytial Virus (RSV) can cause severe illness in adults, leading to respiratory and non-respiratory complications, functional decline, hospitalisation, and death. OBJECTIVES:This study describes French patients aged ≥50 years hospitalised with RSV (2015-2022) and their care pathways, including hospitalisation and outpatient healthcare use and costs. METHODS:Data were extracted from the French National Health Data System (SNDS). Patients were classified into four risk groups (high: immunocompromised; medium: underlying predisposition; other; no comorbidities) and four age groups (50-59, 60-64, 65-74, ≥75 years). Healthcare use (laboratory tests, imaging, pharmacy, GP visits, rehospitalisations) and costs were analysed across three periods: 60-30 days pre-hospitalisation (reference period), index hospitalisation, and 30 days post-hospitalisation. RESULTS:We identified 15,509 RSV-related hospitalisations for 15,169 adults ≥50 years. Median age was 80 years, with age ≥75 years comprising 61.7% of the cohort. 15.9% were high risk, 71.4% medium risk, 4.8% other, and 7.8% had no comorbidities. Intensive care was required in 25.4% of cases. In-hospital mortality was 8.5%, with an additional 3.8% dying within 30 days post-discharge. Rehospitalisation occurred in 17.8% of patients, nearly half for cardiorespiratory causes. Median index hospitalisation cost was €4,252 (Q1; Q3: €3,077; €7,007), and post-hospitalisation costs increased across all ages and risk profiles compared to the reference period. CONCLUSION:RSV imposes a substantial hospitalisation and cost burden in adults ≥50 years, especially older patients and those with comorbidities. Expanded preventive vaccination strategies could help reduce this impact.
BACKGROUND:To provide targeted antimicrobial treatment in lower respiratory tract infections (LRTIs), obtaining a microbiological diagnosis is a prerequisite. Despite guideline recommendations, diagnostic sputum sampling is rarely performed in the emergency room (ER). There is a lack of studies comparing microbiological findings from upper and lower respiratory tract specimens, especially for culture. MATERIALS AND METHODS:We conducted a prospective cohort quality study in the ER including 101 adult patients admitted with suspected LRTI between June 2023 and March 2024. Participants provided nasopharyngeal swabs and spontaneous or induced sputum for bacterial culture, and polymerase chain reaction (PCR) detecting viruses as well as bacteria causing atypical pneumonia. Sputum quality was assessed by light field microscopy. RESULTS:PCR detected pathogens in 34.7% and culture in 31.7% of the participants. We observed no difference in the microbiological yield between the sampling sites. Negative and positive percent agreement between sample sites by PCR was 97.1% and 94.1%, respectively, whereas it was 84.1% and 47.8% by culture. Performing sputum induction in participants not able to produce spontaneous sputum significantly increased the proportion of participants with a microbiological diagnosis. Only one mild adverse event occurred in the 62 participants who underwent sputum induction. CONCLUSIONS:In this study, sampling site for PCR analyses was of less importance in LRTI. For culture, agreement between sampling sites was poor, and sputum probably provides more representative results than nasopharyngeal specimens in LRTI. Sputum induction is feasible and safe and should be encouraged when patients cannot produce spontaneous sputum.
BACKGROUND:Rubella immunity plays a key role in preventing congenital rubella syndrome, but longitudinal data on antibody stability remain limited. OBJECTIVE:To evaluate rubella IgG seroprevalence, seroconversion, and changes in rubella IgG concentrations over time. METHODS:We conducted a retrospective cohort study of 2,022 consecutive individuals from Region Zealand, Denmark, each with at least two serum samples submitted for routine rubella IgG testing between 11 September 2018 and 30 May 2025. Pairedsamples from each individual were analysed. RESULTS:At baseline, 88.6% of participants were seropositive, increasing to 90.6% at follow-up. The cohort was predominantly female (99.4%) and mean age at first sample was 29.8 years. Among initially seronegative individuals, 75 seroconverted, while 34 individuals initially seropositive seroreverted. Median IgG levels among seroconverts were 23.5 IU/mL (range 10-350 IU/mL). Individuals who remained seropositive showed a modest yet statistically significant median decrease of 8.4% between the first and second samples (Hodges-Lehmann ratio = 0.92, 95% CI: 0.91-0.93, p < 0.0001), with minimal association between antibody change and time interval (Spearman's ρ = -0.058, p = 0.015). CONCLUSIONS:In this cohort of routinely tested individuals, rubella IgG levels remained broadly stable, indicating sustained rubella seropositivity over time. Seroconversion and seroreversion occurred in a small subset of individuals, supporting the continued monitoring of rubella immunity, particularly among women of reproductive age. Maintaining high vaccination coverage remains important to sustain rubella elimination and prevent congenital rubella syndrome.
OBJECTIVE:This study aimed to describe epidemiology and management of severe surgical site infections (SSIs) following cochlear implantation (CI) and to identify risk factors. METHODS:A retrospective monocentric study of all CI procedures was performed at our tertiary referral centre between January 2018 and December 2023. Data on patient demographics, clinical features and postoperative infections were collected. Severe SSIs were defined as abscess, skin flap necrosis or device extrusion requiring hospitalisation and/or IV antibiotics. Univariate and multivariate analyses were performed to identify risk factors. RESULTS:Of the 383 CIs, 3.6% (n = 14) developed severe SSIs. A salvage surgery was attempted in 85.7% of cases and the device explantation rate was of 71.4%. Staphylococcus aureus and Pseudomonas aeruginosa were the most identified pathogens. Chronic otorrhea was identified as a statistically significant risk factor for severe SSI (p < 0.001). No significant associations were found with obesity, tobacco use, diabetes, bilateral implantation or implantation renewal. CONCLUSIONS:Severe SSIs following CI are rare but challenging to treat, with a poor outcome. Chronic otorrhea appears to be a significant risk factor. Early intervention with IV antibiotics followed by salvage surgery may help avoid explantation.
BACKGROUND:Although the availability of high-quality surveillance data is critical to inform efforts to reduce the major burden of bloodstream infections (BSIs), there remains a paucity of comprehensive population-based investigations worldwide. OBJECTIVE:To describe the rationale and protocol development of the Queensland BSI (QBSI) study. METHODS:Population-based laboratory surveillance was performed for all BSIs occurring in the publicly funded healthcare system in Queensland, Australia during 2000-2023. Linkages to statewide hospital admissions and vital statistics databases have been performed to determine clinical determinants and mortality outcomes for a minimum of 1 year post-BSI. RESULTS:Standardised definitions were developed to identify incident episodes of BSI and classify them according to type of onset. More than 3.7 million blood cultures were processed during the study period of which a total of 444,279 positive blood cultures were initially identified. Hospital registrations statewide within two years before index culture and one year after were included (n = 2,425,688 with 10,341,136 associated International Statistical Classification of Diseases (ICD) codes during 2000-2023). Comorbidities were classified using previously developed ICD-based algorithms for adults and children and all-cause case-fatality at 30, 90 and 365 days was chosen as the primary outcome measure. CONCLUSIONS:The QBSI study is an evolving program designed to comprehensively examine the epidemiology and outcome of BSIs occurring among residents of this large Australian state. Our aim is to share our experiences to support the development of collaborating centres elsewhere to accelerate epidemiology knowledge and ultimately reduce the major burden due to BSI in populations worldwide.
INTRODUCTION:This systematic review and meta-analysis examined the efficacy of insecticide-treated nets (ITNs) in reducing malaria incidence and malaria-related mortality among vulnerable populations. METHODOLOGY:A comprehensive search of Scopus, Medline, and CINAHL (up-to-April 2, 2026) identified experimental studies (randomised and cluster-randomised trials) evaluating the effect of ITNs impact for malaria control, and the protocol was registered in PROSPERO (CRD42024609183). Pooled-effect-sizes [rate-ratios(RRs) and odds-ratios (ORs)] were calculated, and meta-regression was conducted to examine study-level sources of variation in effect estimates. RESULTS:A total of 25 studies were included in the meta-analysis, including 19 assessing malaria-incidence and 6 evaluating malaria-related mortality. Overall, ITNs demonstrated strong protective effects across diverse populations. The pooled-estimate using a random-effects model showed a 29% reduction in malaria incidence among ITNs users in Africa (RR = 0.71; 95% CI: 0.54-0.93; p = 0.0133; I2 = 64%) and 68% in Asia (RR = 0.32; 95% CI: 0.17-0.62; p = 0.0007; I2 = 89.0%). The pooled-odds-ratio for malaria incidence in African studies indicated a 40% reduction in odds (OR = 0.60; 95% CI: 0.44-0.82; p = 0.0011; I2 = 86.2%), whereas the pooled-rate-ratio for malaria-related-mortality in Asia was 0.82 (95% CI: 0.77-0.89; p < 0.0001; I2 = 0) from 5 studies, indicating an 18% reduction in mortality. Meta-regression on 17 studies confirmed an overall significant protective effect of ITNs against malaria(β = -0.84; 95% CI: -1.68 to -0.01; p = 0.05). CONCLUSION:ITNs reduce malaria transmission, though effectiveness varies across regions due to ecological, epidemiological, and implementation differences.
BACKGROUND:Ethnic inequalities in COVID-19 outcomes are extensively documented, yet underlying causes remain unclear. We investigated ethnic disparities in clinical severity at admission with COVID-19 and their relation to mechanical ventilation (MV), 60-day mortality, and long COVID. METHODS:Retrospective cohort study of adults (≥18 years) admitted with COVID-19 (March 2020-March 2022). Clinical and sociodemographic data extracted from patient records were linked to national register data. Using logistical regression, competing risk, and Cox proportional hazards models, we estimated risk of high-flow oxygen upon admission, MV, 60-day mortality, and long COVID comparing ethnic minority patients with patients of Danish origin. RESULTS:Of 1610 patients, 39.1% were ethnic minority patients. Ethnic minorities were younger, had longer symptom duration (7 vs 6 days, p < 0.001), and a higher risk of requiring high-flow oxygen upon admission (OR 1.41, 95% CI: 1.12;1.79) than patients of Danish origin until adjusted for age. However, ethnic minorities were not at higher risk of MV (HR 1.00, 95% CI: 0.69;1.44), 60-day mortality (HR 0.81, 95% CI: 0.61;1.09), long COVID (HR 0.82, 95% CI: 0.56;1.19) or related symptom diagnosis (HR 1.32, 95% CI: 0.85;2.05). CONCLUSION:While ethnic minorities presented later and more severely ill at admission with a higher risk of receiving high-flow oxygen, their risk of MV, 60-day mortality, and long COVID were comparable to patients of Danish origin. This was largely explained by a substantial difference in age. Our findings emphasise the need for public health interventions to ensure equitable and timely healthcare access for all populations.
OBJECTIVES:To investigate if COVID-19 increases the odds of fatigue, headache, dizziness, concentration difficulties, and memory impairment as well as at least three of these symptoms, at <4 weeks, 4-12 weeks, and >12 weeks after COVID-19. Additionally, we investigated whether symptoms were influenced by severity of COVID-19, sex, and pre-infection COVID-19 vaccination. STUDY DESIGN AND METHODS:This study utilised data from the DanishBiCoVac cohort and national registers. The BiCoVac cohort collected information about symptoms through four questionaries distributed between May 2021 and May 2022. Participants with COVID-19 were matched to participants without COVID-19.Three matching samples were created according to time since COVID-19. Logistic regression was performed for the association between COVID-19 and each outcome. RESULTS:Participants with COVID-19 within 0-4 weeks had higher odds of reporting all outcomes compared to participants without COVID-19. Between 4 and 12 weeks after COVID-19, the odds of symptoms were also higher, although attenuated. After 12 weeks, participants with COVID-19 also had higher odds of symptoms except for concentration difficulties compared to those without COVID-19. Odds for symptoms were highest for participants reporting severe infection. Prior COVID-19 vaccination might weaken the association while no clear modification was found for sex. CONCLUSION:Participants with COVID-19 had higher odds of all outcomes, especially within the first 4 weeks. After 12 weeks, the ORs were attenuated but still indicated an association for all outcomes except concentration difficulties. Individuals vaccinated against COVID-19 tended to report fewer symptoms after COVID-19. Participants with severe COVID-19 had the highest odds of symptoms.
