The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the need to update evidence on coronavirus disease 2019 (COVID-19) severity and disease burden, and better understand the impact on prevention, treatment, and healthcare systems. This systematic review aimed to determine relative disease severity, through comparative measures of hospitalization, intensive care unit admission and mortality, between SARS-CoV-2 variants of concern emerging since Omicron was first identified. A protocol was registered a priori (PROSPERO ID: CRD42024619193). Systematic searches of MEDLINE and EMBASE databases were conducted in November 2024 and supplemented by conference searches from 2022-2024. Population, Exposure, Comparisons, Outcomes (PECO) criteria were used to screen publications for inclusion. Critical appraisal tools published in the Joanna Briggs Institute (JBI) Handbook for Evidence Synthesis were used to assess the risk of bias of the primary studies included. The outcomes associated with Omicron variants, identified by sequencing or predominance periods, included hospitalization, admission to intensive care, death, and various composite endpoints. Thirty-two studies fulfilled the eligibility criteria, most reported on relative disease severity for early Omicron BA.5 (n = 23) and XBB (n = 24) variants. Overall, COVID-19 severity appeared largely comparable across the various Omicron subvariants. Among the subset of studies that directly compared various severity outcomes to earlier SARS-CoV-2 variants (n = 7), some reported modest increases or decreases in severity. However, these differences were generally not statistically significant. Five studies stratifying outcomes by the presence of comorbid conditions noted that comorbidities were predictors of significantly worse COVID-19 disease outcomes (p = 0.000-0.027). Overall, this systematic review found the severity of COVID-19 disease to be comparable among Omicron subvariants. As SARS-CoV-2 subvariants continue to emerge, these results highlight the continuing need for vaccination against SARS-CoV-2 infection alongside early antiviral intervention to support short-term management and long-term reduction of COVID-19-associated morbidity and mortality.

The observational phase IV study through an active surveillance system aimed to assess the safety of the subunit influenza vaccine in healthy individuals aged ≥ 3years and explore the feasibility of using an active adverse event (AE) surveillance system based on a WeChat Mini Program incorporating electronic diary cards (e-diary cards) in China. Between October 30, 2023, and April 28, 2025, a multi-center, open-label, single-arm prospective active surveillance study was conducted. Healthy individuals aged 3years and above who voluntarily and at their own expense came to the outpatient department to receive the target vaccine (Ab&B Biotech Co., Ltd., Jiangsu, China) were recruited as research participants. The WeChat Mini Program was employed to record baseline information and the occurrence of AEs and adverse drug reactions (ADRs) within 28days after vaccination. A post hoc subgroup analysis was conducted to assess the safety characteristics of participants in different age groups. Among the 42,881 participants, 495 (11.54‰) reported a total of 682 AEs. No vaccine-related serious adverse events (SAEs) were reported. A total of 293 participants (6.83‰) reported 374 ADRs. Among these, 29 participants (0.68‰) reported 34 unsolicited ADRs, including pharyngalgia (n = 10, 0.23‰) and rhinorrhea (n = 4, 0.09‰) among others. The incidence rates (IR) of AEs across 3-8, 9-17, 18-64, ≥ 65years groups, from youngest to oldest, were 16.29‰ (n = 269), 10.63‰ (n = 58), 10.53‰ (n = 145), and 3.21‰ (n = 23). A statistically significant difference in AE incidence was observed among the age groups (P < 0.001). The vaccine demonstrated a favorable safety profile in healthy individuals aged 3years and above. Moreover, the active surveillance method with the Mini Program was helpful in detecting very rare ADRs. NCT073326896. Retrospectively registered.

Malaria elimination remains a global public health priority, particularly in low- and middle-income countries. India has set a target of eliminating malaria by 2030, making it essential to understand gaps in healthcare access, utilization, and preventive practices in endemic areas to guide focused interventions to achieve national and global malaria elimination targets. A subnational, cross-sectional study surveying 37,849 households in ten malaria-endemic states in India, which covered 177,644 individuals, was carried out to estimate the health service and long-lasting insecticidal net (LLIN) utilization for febrile illness and malaria. The study found that the accessibility of a government healthcare facility was within 2.5km (interquartile range [IQR] 1-5km), with 57.4% of febrile individuals visiting a government healthcare center or approaching a government-designated healthcare provider for fever within 24-48h. Adequate knowledge and behavior regarding prevention were observed in 89.2% households, while 73.6% households reported using LLINs regularly. Lack of formal education and belonging to the tribal population were found to be high risk factors for malaria. Healthcare-seeking behavior played a crucial role in malaria burden. This study highlights the gap between accessibility of health facility and its utilization, as well as LLIN ownership and its regular utilization.

Several risk factors for progression to severe COVID-19have been identified, but whether multiple concomitant risk factors (risk stacking) further increase risk remains unknown. We sought to identify outpatient populations at the highest risk for severe COVID-19 using risk factor stacking. We conducted a retrospective cohort study of Veterans Affairs (VA) outpatient adults (≥ 18years) at high risk for severe COVID-19 with a positive SARS-CoV-2 test or COVID-19 diagnosis between April 1, 2022 and August 21, 2024. Severe COVID-19 was defined as COVID-19-related hospitalization or all-cause mortality within 30days. Logistic regression models were used to quantify the impact of combinations of multiple risk factors (stacked risks) on severe COVID-19. Risk factors, selected based on prevalence and CDC criteria, included age ≥ 50years, chronic lung disease, cancer, neurological conditions/cerebrovascular disease, chronic kidney disease, chronic liver disease, diabetes mellitus, heart conditions, mental health conditions, obesity, smoking, immunosuppression, hypertension, and not being up to date on COVID-19 vaccination. Among 379,144 VA outpatients with COVID-19, 1.5% (5801) had severe outcomes within 30days. Risk increased with each additional factor from two (adjusted odds ratio [aOR] 2.10, 95% confidence interval [CI] 1.37-3.23) to 14 risk factors (aOR 43.49, 95%CI 4.94-382.66) compared to one. Overall, 239 significant risk factor combinations were identified. Hypertension appeared in 196 combinations (82.0%), not up-to-date on COVID-19 vaccination in 173 combinations (72.4%), smoking in 168 combinations (70.3%), and heart conditions in 154 combinations (64.4%). The combination with the highest risk (aOR 35.25, 95%CI 16.06-77.37) included age ≥ 50years, chronic lung disease, neurological conditions/cerebrovascular disease, diabetes mellitus, heart conditions, smoking, hypertension, and not being up-to-date on COVID-19 vaccination. In this large national cohort, severe COVID-19 risk increased with the number of risk factors present. Patients with multiple overlapping risk factors who were not vaccinated were at the highest risk for severe COVID-19. As recommendations have shifted toward risk-based clinical decision-making, identifying patients with particularly high-risk combinations of conditions is increasingly important to support targeted vaccination and timely antiviral treatment.

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among older adults. Limited information is available in Israel regarding RSV outcomes, particularly compared to influenza, to guide strategies for RSV vaccination. This study aimed to characterize RSV infection and predictors of clinical outcomes among hospitalized adults aged ≥ 60years in Israel between 2016 and 2023, and to compare disease severity and outcomes with those of seasonal influenza hospitalizations. A retrospective analysis was conducted of hospitalized adults aged ≥ 60years with positive RSV or influenza confirmed via standard-of-care RT-PCR between 2016 and 2023. The primary outcome was a composite of intensive care unit (ICU) admission, mechanical ventilation, vasopressor support, or 30-day mortality. Cardiovascular complications were recorded. An inverse probability treatment weighting (IPTW) was used to adjust for potential confounding. Weighted and unweighted relative risks (RRs) were estimated to compare clinical outcomes between RSV and influenza. Overall, 817 RSV-positive and 2113 influenza-positive patients were included. Among patients with RSV, 30-day and 90-day mortality rates were 11.9% and 18.8% respectively; ICU admission was required for 10.6%, mechanical ventilation for 6.4%, and vasopressor support for 6.5%. Tachyarrhythmia was documented in 17.7% and ischemia in 9.9%. Predictors of the composite primary outcome included chronic pulmonary disease, lower respiratory tract infection, hypothermia, elevated pulse, lower blood pressure and increased creatinine. In IPTW-adjusted analyses, RSV infection had a trend for increased risk for the composite primary outcome (RR 1.03, 95% confidence interval [CI] 1.00, 1.06) and 90-day mortality (RR 1.02, 95%CI 0.99, 1.05) compared with influenza. Among hospitalized older adults, RSV infection carries considerable morbidity and mortality and may have a higher risk for poor clinical outcomes compared with influenza. These findings support the prioritization of RSV vaccination programs among older adults.

Adherence to guideline recommendations on the use of echocardiography in all patients with Staphylococcus aureus bacteremia (SAB) is heterogeneous. This study aims to validate the VIRSTA and VIRSTA+ scores as tools for risk stratification to identify patients at low risk of infective endocarditis (IE) and support the prioritization of transthoracic echocardiography (TTE). This is a retrospective analysis of a prospectively assembled cohort of adult patients with SAB admitted between January 2006 and December 2022. Patients who did not undergo an echocardiogram were excluded, as well as those who died within the first 48h, those receiving antibiotic treatment during blood culture collection, and individuals without recorded time to positivity (TTP). VIRSTA and VIRSTA+ scores were calculated from clinical records, and their diagnostic performance was assessed. IE diagnosis, defined using modified Duke criteria, was compared between patients classified as low and high risk according to these scores. Of a total of 1668 episodes diagnosed with SAB, 798 adult patients were included in the final analysis. Median (interquartile range [IQR]) TTP was 8 (7-11) h for IE cases and 12 (9-15) h for non-IE cases. In VIRSTA≥3 episodes, IE was observed in 108 (19%) patients, compared with 1/238 (0.4%) with VIRSTA<3 corresponding to a sensitivity of 99%, a specificity of 34.4% with a positive predictive value of 19.3%, and a negative predictive value (NPV) of 99.5%. The single patient with IE and a VIRSTA<3 had a TTP<11.5h. Accordingly, the NPV of VIRSTA+ achieved 100%. VIRSTA and VIRSTA+ demonstrated high NPV for risk stratification in SAB, suggesting that they could help prioritize procedures and guide decision-making in clinical practice, particularly in resource-constrained settings.

Older adults (OAs) and individuals with underlying comorbidities are at increased risk for severe respiratory syncytial virus (RSV) disease (e.g., lower respiratory tract disease [LRTD]) and related adverse outcomes. However, RSV is underdiagnosed and underestimated in OAs, posing a growing concern in super-aged societies like Japan. This prospective, multicenter, epidemiological study (Nagasaki ROAD) aimed to enroll approximately 2700 participants aged ≥ 50years with acute respiratory infection (ARI) seeking care at outpatient/emergency/inpatient settings at 15 medical institutions/hospitals/clinics in Nagasaki and its surroundings. Enrolled participants were followed for 180days. RSV positivity in nasopharyngeal swab samples, detected by reverse transcription polymerase chain reaction, served as the primary diagnosis of RSV-related ARI/LRTD (RSV-ARI/LRTD). Hospital-wide and non-hospital-wide screening were adopted based on site-level operational realities and clinical workflows. Data at enrollment (baseline/day 1) were analyzed from 1056 participants who were recruited between April 1, 2024 and March 31, 2025. The approximate positivity rate of RSV-ARI was 5.0% (n = 53), peaking from June to September 2024. The approximate positivity rate of SARS-CoV-2-ARI was 25.4% (n = 268), and influenza-ARI was 19.6% (n = 207). Hospitalization at or within 7days of day 1 was observed in 20.8% (n = 11) of participants with RSV-ARI, 13.1% (n = 35) with SARS-CoV-2-ARI, and 13.0% (n = 27) with influenza-ARI. The most common comorbidities-of-interest were asthma (17.0% [n = 9]), chronic obstructive pulmonary disease (15.1% [n = 8]), and type 2 diabetes mellitus (7.5% [n = 4]) in participants with RSV-ARI. The observed need for oxygen supplementation was higher in participants with RSV-ARI (13.2% [n = 7]) than with SARS-CoV-2-ARI (3.4% [n = 9]) or influenza-ARI (8.7% [n = 18]). These year 1 results contextualize the RSV disease burden in OAs aged ≥ 50years in Nagasaki, Japan, providing an important basis for understanding RSV in Japanese OAs; findings complement existing evidence. Future analyses of all clinical outcomes through 180-day follow-up could further inform targeted prevention strategies in this population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global public health concern. Anti-nucleocapsid (anti-N) serology is a key tool for identifying prior infection and supporting population-level surveillance. This study evaluated the clinical performance of the Elecsys® Anti-SARS-CoV-2 Anti-N immunoassay on the Cobas® e 601/602 immunoassay analyzer using real-world data from patients with polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection. The study aimed to provide data which, along with clinical study data, supported the transition from Emergency Use Authorization of the assay to full clearance in the USA. We conducted a retrospective review of electronic medical records and laboratory information system data from patients who presented to Columbia University Irving Medical Center from March 2020 to March 2021. Eligible participants were symptomatic, unvaccinated individuals with PCR-confirmed SARS-CoV-2 infection who subsequently underwent serologic testing. Serologic results were categorized by days post symptom onset (DPSO): 0-7, 8-14, and ≥ 15days. To avoid repeated measures, only the first serologic result per patient within each DPSO category was included. The primary endpoint was positive percent agreement (PPA) for nonimmunocompromised individuals tested at ≥ 15 DPSO, with a prespecified acceptance threshold of ≥ 90%. A total of 585 serologic tests from 567 patients (77, 45, and 463 samples, in DPSO categories of 0-7, 8-14, and ≥ 15days, respectively) were evaluated. Among nonimmunocompromised individuals with samples collected ≥ 15 DPSO (N = 285), the PPA was 96.49% (95% confidence interval 93.66%, 98.08%), fulfilling the predefined acceptance criterion. PPA was also consistent across demographic subgroups, supporting the generalizability of the findings. This study demonstrates the feasibility of generating robust clinical evidence for regulatory purposes using real-world data. The clinical performance of the Elecsys Anti-SARS-CoV-2 immunoassay was confirmed using data collected under routine conditions during the pandemic, complementing data from controlled clinical studies and contributing to informed regulatory decision-making.

Outpatient parenteral antimicrobial therapy (OPAT) enables effective infection management outside hospital settings, offering clinical and economic benefits. While widely adopted internationally, its implementation in Italy remains fragmented. This study aimed to systematically map the use of OPAT in Italy to identify research and policy priorities. A scoping review was conducted following the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews guidelines. The protocol was registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/GX8S6 ) in August 2025. Searches were performed across PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus. Eligible studies included primary research on OPAT in Italy, with no restrictions on publication date or language. Data extraction focused on study characteristics, OPAT indications, antimicrobial agents, delivery models, and outcomes. Twenty-three studies were included, mostly observational and single-center, published between 2000 and 2025. OPAT was primarily delivered at home or in infusion centers. The most frequent indications were infections of bone and joint, skin and soft tissue, and the respiratory tract. Ceftriaxone was the most used antimicrobial. Delivery was mainly intravenous, often via elastomeric pumps and peripheral or central venous access. Reported outcomes were generally favorable, with cure or improvement rates exceeding 90% in several studies. Adverse events were infrequent, mostly associated with drug reactions or catheter-related complications. Patient satisfaction was consistently high. Economic evaluations were limited but suggested cost savings primarily driven by reductions in hospital stays. OPAT is feasible and increasingly used in Italy, but remains inconsistently implemented across regions. Broader adoption would benefit from national guidance, standardized protocols, and integrated stewardship frameworks. Future research should address comparative and cost-effectiveness, as well as equitable access, to support systematic scale-up aligned with national health priorities on antimicrobial resistance and community-based care.

Viral hepatitis remains a significant challenge for global public health and a leading cause of liver-related morbidity and mortality worldwide, with most cases caused by five hepatotropic viruses: hepatitis A, B, C, D, and E. The World Health Organization has established a goal to eliminate viral hepatitis as a public health threat by 2030. In recent years, advancements in our understanding of its pathogenesis have significantly propelled the development of antiviral drugs, particularly for hepatitis C, for which we now have highly effective therapies with cure rates exceeding 95%. However, achieving complete cures for hepatitis B and D continues to pose challenges, and effective treatments for hepatitis A and E are still lacking. A comprehensive understanding of the latest treatment advancements is crucial for guiding future drug development. This article reviews the most recent advancements in pharmacological interventions for viral hepatitis, summarizes current treatment methods, and provides an outlook on future research and therapeutic strategies, with the aim of improving patient outcomes and alleviating the global burden of liver diseases.