Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infec-tion and a major contributor to lower respiratory tract disease, hospitalization, and intensive care admission in young infants. The burden of severe disease is greatest during the first months of life, when active infant immunization is not yet feasible or may not provide sufficiently rapid protec-tion. The recent availability of prefusion F protein–based vaccines and long-acting monoclonal antibodies has transformed the RSV prevention landscape, making protection during early in-fancy an achievable public health objective. Methods: This consensus document summarizes and critically appraises updated evidence on RSV epidemiology, disease burden, seasonality, pre-ventive strategies, and implementation challenges, with a specific focus on maternal immuniza-tion. Evidence was reviewed in relation to infant protection, transplacental antibody transfer, optimal timing of vaccination during pregnancy, integration into antenatal care, and the posi-tioning of maternal vaccination alongside infant monoclonal antibody prophylaxis. Results: RSV imposes a substantial clinical and economic burden in infancy, including among previously healthy term infants, with the most severe outcomes concentrated in the first months after birth. Post-pandemic changes in RSV circulation have reduced the predictability of seasonal patterns, challenging prevention strategies based solely on traditional RSV seasons. Maternal RSV vac-cination provides passive protection to newborns through transplacental transfer of neutralizing antibodies and has demonstrated efficacy in reducing medically attended RSV-associated lower respiratory tract infection, severe disease, and hospitalization in early infancy. However, re-al-world effectiveness depends on several factors, including gestational age at vaccination, the interval between vaccination and delivery, prematurity, maternal immune response, vaccine uptake, and local RSV epidemiology. The coexistence of maternal vaccination and infant mono-clonal antibody prophylaxis requires clear, coordinated recommendations to prevent gaps in protection and support efficient resource allocation. Conclusions: Maternal immunization is a clinically relevant strategy to protect infants against RSV during their period of greatest vulner-ability. Successful implementation will require integration into routine antenatal care, adaptation to local epidemiology, coordination with monoclonal antibody programs, and continued sur-veillance of effectiveness, safety, uptake, and equity. A flexible prevention framework combining maternal vaccination and infant monoclonal antibody prophylaxis, according to local needs and individual risk, has the potential to substantially reduce RSV-associated morbidity, hospitaliza-tions, and healthcare burden in early infancy.

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

BACKGROUND:The alveolar sac, which serves as the primary site for gas exchange, comprises alveolar type 1 (AT1) and alveolar type 2 (AT2) cells. These epithelial cells initiate immune responses upon encountering external stimuli. However, the influenza virus infection patterns and antiviral responses exhibited by different types of alveolar epithelial cells remain understudied. This study aimed to investigate the differential susceptibility and antiviral responses of AT1 and AT2 cells during influenza virus infection. METHODS:Immunofluorescence staining was performed to determine the spatial distribution of influenza A virus (IAV; H1N1). Primary murine epithelial in vitro culture models, including an AT2 sphere culture and an AT1 differentiation model, were established to elucidate the mechanisms underlying cellular susceptibility to IAV. Bulk RNA sequencing and quantitative polymerase chain reaction were performed to characterize the cellular responses to viral infection. RESULTS:Mouse AT2 cells exhibited greater susceptibility to H1N1 than did AT1 cells. The in vitro primary epithelial cell culture models mimicked the in vivo cellular phenotype. They further reproduced the in vitro finding of relatively high viral replication in AT2 cells. Mechanistically, no significant difference was observed between AT1 and AT2 cells in the expression of α-2,3 or α-2,6 sialic acid (viral receptors). However, RNA sequencing revealed that gene ontology terms such as the response to viral infection, negative regulation of the viral life cycle, and regulation of type I interferon (IFN) production were enriched in AT1 cells. This finding was validated using quantitative polymerase chain reaction. From 12 to 48 h after infection, the expression levels of types I and III IFNs, chemokines, and IFN-stimulated genes remained lower in AT2 cells than in AT1 cells. CONCLUSION:Our findings indicate the localization of IAV in alveoli and highlight the vulnerability of AT2 cells, which exhibit delayed immune responses, resulting in increased viral replication.

Respiratory syncytial virus (RSV) imposes a significant burden on global health, particularly among young children and older adults. Despite extensive global surveillance, granular epidemiological data from Hong Kong—a densely populated subtropical region—remain sparse. This study bridges this gap by analysing 11 years of population-level data, including the unprecedented impact of COVID-19 and post-pandemic resurgence.Clinical Outcomes of Hospitalized RSV Cases and RSV Cases by Comorbidity Type (2013-2024)Cumulative Incidence (2013-2024) We conducted a retrospective population-based study using surveillance data from 2013 to 2024 in Hong Kong. RSV cases were extracted monthly, and the cumulative incidence (per 100,000 population) was calculated annually, stratified by age (≤2, 3–64, ≥65 years) and sex. Temporal trends, seasonal patterns, comorbidities, risk factors, and clinical outcomes (Intensive Care Unit (ICU) admissions, mortality, and ventilation usage) were examined. Seasonal-Trend decomposition using LOESS (STL) was applied under two scenarios:Filtering out pandemic years (2020–2022) to create a discontinuous time series.Including pandemic years (2020–2022) to analyze disruptions and recovery patterns.RSV Hospitalization and seasonal index (2013-2024)STL decomposition Among 43,588 RSV cases, incidence peaked in 2017 (73.4/100,000) and 2023 (121.0/100,000). Children ≤2 years faced the highest burden (414.6/100,000 in 2023), while adults ≥65 years saw a 167% rise (7.6 to 20.3/100,000, 2013–2024). Seasonal peaks (July–September) were disrupted during COVID-19 but rebounded sharply in 2023, with severe outcomes: 253 ICU admissions and 186 deaths. STL decomposition showed pandemic-related suppression, followed by amplified seasonality post-COVID. Prematurity (10.3%) and chronic obstructive pulmonary disease (6.8%) were key risk factors. RSV remains a growing public health concern in Hong Kong, heavily impacting young children and older adults. The COVID-19 pandemic disrupted RSV transmission, but the post-pandemic resurgence was more intense. STL decomposition offered valuable insights into seasonal and temporal trends, highlighting the need for time-series modeling in predicting viral behavior. Enhanced surveillance, maternal vaccination, pediatric monoclonal antibodies, and targeted preparedness are critical to reducing RSV-related morbidity and mortality in high-risk groups. All Authors: No reported disclosures

OBJECTIVES:To evaluate how oral antivirals (molnupiravir and nirmatrelvir-ritonavir) and COVID-19 vaccination affect SARS-CoV-2 viral kinetics in adults aged ≥60 years with symptomatic COVID-19 hospitalized in Hong Kong. METHODS:We analyzed viral burden using cycle threshold (Ct) values from patients admitted between May 23, 2022 and Jan 23, 2023 when Omicron subvariants predominated. Viral trajectories were modelled with log-polynomial random-effects framework to estimate daily Ct values and duration of potentially infectious shedding (time to Ct ≥30). We then examined how antiviral timing and vaccination history modified these virological outcomes. RESULTS:Among 3759 symptomatic COVID-19 patients included, 1318 received molnupiravir, 1613 received nirmatrelvir-ritonavir. Compared with no treatment, nirmatrelvir-ritonavir was associated with shorter shedding (mean difference -2.4 days, 95% CIs: -2.7, -2.2), especially with earlier initiation, whereas molnupiravir had a smaller effect (-0.6 days, 95% CIs: -0.9, -0.3). The virologic effect of nirmatrelvir-ritonavir was greater in unvaccinated than vaccinated patients, while the effect of molnupiravir did not differ notably by vaccination status. CONCLUSION:Early nirmatrelvir-ritonavir substantially shortens SARS-CoV-2 shedding in older adults, especially if unvaccinated. These findings support timely antiviral use and consideration of vaccination history when optimizing treatment for high-risk populations.

Background: Systemic corticosteroids are the standard of care for severe COVID-19, but the real-world comparative effectiveness of adding baricitinib or tocilizumab remains uncertain in older, multimorbid populations across diverse pandemic phases. We evaluated the association between targeted immunomodulators and 28-day clinical outcomes compared with corticosteroid monotherapy, and explored whether the association varied by sex, age, or comorbidity. Methods: We conducted a retrospective cohort study using territory-wide electronic health records from the Hong Kong Hospital Authority. Eligible patients had a first confirmed COVID-19 diagnosis between Jan 1, 2020, and Jan 31, 2024, were hospitalised within 5 days, required ventilatory support, and initiated either corticosteroid monotherapy or baricitinib/tocilizumab (with or without concurrent corticosteroids) within 5 days of diagnosis. Inverse probability of treatment weighting (IPTW) balanced baseline characteristics measured at or before the index date. The primary outcome was 28-day all-cause mortality, analysed using weighted Cox proportional hazards models and additionally summarised as a difference in 28-day restricted mean survival time (RMST). We analysed secondary outcomes (28-day ICU admission and mechanical ventilation), accounting for the competing risk of death. Findings: Of 2,292 eligible patients, 1,634 (71·3%) received corticosteroid monotherapy, and 658 (28·7%) received baricitinib or tocilizumab (359 [54·6%] baricitinib, 299 [45·4%] tocilizumab). After IPTW, all standardised mean differences were <0·1. The weighted cohort had a mean age of approximately 73·5 years and was 63·5% male. Baricitinib or tocilizumab was associated with lower 28-day all-cause mortality (incidence rate 160·24 vs 202·69 per 10,000 person-days; adjusted hazard ratio [aHR] 0·834, 95% CI 0·701–0·993; p=0·042). No significant differences were observed for 28-day ICU admission (aHR 0·367, 95% CI 0·043–3·106) or mechanical ventilation (aHR 0·555, 95% CI 0·050–6·209); both secondary analyses were severely underpowered. Pre-specified subgroup analyses showed directionally consistent estimates across sex, age, and comorbidity strata, with no significant interaction (sex p=0·187; CCI p=0·334; age <80/≥80 p=0·239). Interpretation: In a predominantly older cohort of hospitalised patients with severe COVID-19, receipt of baricitinib or tocilizumab was associated with lower 28-day mortality compared with corticosteroid monotherapy.

Blood pressure (BP) variability is an independent risk factor for cardiovascular disease. Gut microbiome (GM) regulates BP, but its association with BP variability remains unclear. We examined the association of GM, determined by stool shotgun metagenomic sequencing, with 24-hour BP average real variability (ARV) assessed by ambulatory BP monitoring in 235 community-dwelling adults from Hong Kong (111 men and 124 women, mean age 54 ± 6 years) using covariate-adjusted statistical models. The GM alpha diversity was negatively associated with systolic BP (SBP) ARV in the full cohort, driven by women. In men, beta diversity of both GM species and function was associated with SBP ARV, while Bacteroides nordii and the steroid hormone biosynthesis pathway had a positive association with SBP ARV. Bacteroides nordii emerged as the key species driving the significant positive association of steroid hormone biosynthesis and other pro-pathogenic pathways with SBP ARV, including lipopolysaccharide biosynthesis, phenylalanine, and sulfur metabolism in men, warranting further investigation for its causal role. We demonstrated distinct signatures of GM dysbiosis, composition, and function with minimal overlap between men and women with increased 24-hour SBP variability. Our work suggests that sex differences should be an important consideration in mechanistic and therapeutic investigations of GM-mediated BP variability.

While molnupiravir and nirmatrelvir-ritonavir have demonstrated efficacy in reducing hospitalisation and mortality among unvaccinated, high-risk COVID-19 patients in outpatient settings, their impact on hospitalised adults remains unclear. Preclinical studies and case reports suggest combining these antivirals may reduce viral shedding and enhance survival.Baseline characteristics of eligible COVID-19 patients after the inverse probability of treatment weighting (IPTW)SMD=Standardised mean difference; SD=Standard deviation; IQR = interquartile range; CCI=Charlson Comorbidity Index; ICU=Intensivecare units;†SMD<0.1 indicates balance between groups·†† Level 1: Hospitalised patients with no oxygen therapy; Level 2: Hospitalised patients with oxygen by mask, nasal prongs, non-invasiveventilation or high flow; Level 3: Hospitalised patients with intubation and mechanical ventilation, vasopressors, dialysis, or extracorporealmembrane oxygenationRisk of outcomes for COVID-19 patients receiving combined use of molnupiravir and nirmatrelvir ritonavir compared with patients receiving molnupiravir alone and patients receiving nirmatrelvir-ritonavir alone after weighting This target trial emulation study evaluated the safety and efficacy of combined molnupiravir and nirmatrelvir-ritonavir versus monotherapy in hospitalised COVID-19 adults in Hong Kong. Data were extracted from electronic health records of patients aged 18 and older treated within five days of hospital admission between March 16, 2022, and March 31, 2024. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Outcomes, including all-cause mortality, Intensive Care Unit (ICU) admission, and ventilatory support, were assessed using Cox proportional hazards models.Study flow diagram90-day cumulative incidence of outcomes in recipients of combination treatment with nirmatrelvir-ritonavir and molnupiravir compared to recipients of molnupiravir monotherapy and recipients of nirmatrelvir-ritonavirShared area refers to the 95% confidence interval for the cumulative incidence. The P values indicate the overall P values of the Log-rank test comparing the three treatment groups for each outcome Among 28,355 patients (combination: 1,081; molnupiravir: 8,416; nirmatrelvir-ritonavir: 18,858), IPTW-adjusted analyses showed that nirmatrelvir-ritonavir monotherapy was associated with a significantly lower risk of mortality (HR: 0.62; 95% CI 0.50-0.77; ARR: -3.16%) compared to combination therapy. Risks of ICU admission and ventilatory support were similar across all groups. Patients receiving nirmatrelvir-ritonavir monotherapy also showed lower risks of acute liver injury (HR: 0.53 [95% CI 0.32-0.88]), acute kidney injury (HR: 0.61 [95% CI 0.51-0.74]), and hyperglycaemia (HR 0·73 [95% CI 0.57- 0.93]). Combining nirmatrelvir-ritonavir and molnupiravir does not significantly reduce mortality, ICU admissions, or ventilatory support needs in hospitalised COVID-19 adults. Further randomised controlled trials are needed to confirm these findings. All Authors: No reported disclosures

BACKGROUND:Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination. METHODS:We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list. RESULTS:Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96-313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18-69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85-88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27-74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23-1.29) for unvaccinated and 1.08 (95% CI: 1.05-1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups. INTERPRETATION:COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.

OBJECTIVES:Antimicrobial resistance (AMR) presents significant challenges for the effective treatment of pneumococcal disease (PD), disease prevalence, and vaccine effectiveness caused by S. pneumoniae. We aimed to describe the pattern of AMR among isolates from patients with PD reported in the Hong Kong population from 2012-2021, and to explore the risk factors associated with AMR among patients hospitalized with PD compared to those with susceptible isolates. METHODS:PD-related hospitalizations were identified and grouped into invasive PD (IPD) or non-IPD patients. Electronic health records were collected to calculate the healthcare resource utilization relevant to each IPD/non-IPD patient. We compared the characteristics of patients with IPD/non-IPD caused by non-susceptible isolates (cases) and those without (controls) using a multivariable logistic regression model, looking for risk factors for AMR. RESULTS:The PD incidence trend was stable from 2012 to 2019 with a sudden decrease in 2020, coinciding with the beginning of the COVID-19 pandemic. Overall, 80% of patients had S. pneumoniae non-susceptible to ≥1 antibiotic. The percentage of non-susceptibility found to tetracyclines, macrolides, penicillin, and fluoroquinolones, were 85%, 79%, 23% and 2%, respectively. Overall, 46% of the patients with serotyping results were serotype 3. Significantly increased odds of AMR infection were found among the non-IPD patients aged 2-17 years when compared to older patients (18-64 years). CONCLUSIONS:Measures to reduce non-susceptible S. pneumoniae infections should focus on children and adolescents of school age. Despite the introduction of PCV13 in 2011, serotype 3 and AMR continued to threaten people in the community. Serotype 3-infected patients accounted for nearly half of the patients with PD with serotyping results.

Simnotrelvir is an oral small-molecule antiviral agent targeting the 3C-like protease (3CLpro) of SARS-CoV-2, proven effective against the Delta variant with favorable pharmacokinetics and safety in preclinical study. In this study, we further evaluated the antiviral efficacy of simnotrelvir against a range of emerging Omicron variants, including BA.1, BA.4, BA.5, CH.1.1, XBB.1.5, XBB.1.16, EG.5, and JN.1. In vitro assays with Vero E6 cells confirmed that simnotrelvir exhibited robust antiviral activity across these variants, comparable to the Food and Drug Administration (FDA)-approved drug nirmatrelvir. Additionally, simnotrelvir demonstrated effective inhibition against several nirmatrelvir-resistant SARS-CoV-2 3CLpro mutants, including A260V, Y54A, (T21I + S144A), F140A, H172Y, and E166V. Importantly, simnotrelvir showed better potency against the E166V mutation compared to nirmatrelvir. Resistance selection studies revealed that BA.5 developed reduced sensitivity after 5 and 10 passages, increasing the IC50 values by 3.2 and 4.5-fold, respectively, while HCoV-OC43 showed an 8.3-fold increase after 12 passages. Despite this, simnotrelvir's overall efficacy remains strong. Furthermore, clinical trials demonstrated that combining simnotrelvir with ritonavir significantly shortened symptom resolution in COVID-19 patients. Genomic analysis of treated patients found random nucleotide substitutions but no significant mutations linked to 3CLpro resistance. In conclusion, simnotrelvir shows strong antiviral activity against SARS-CoV-2 variants and maintains a high barrier to resistance, reinforcing its potential as an effective therapeutic option for current and future SARS-CoV-2 variants.

OBJECTIVES:This study aims to investigate the association between elderly patients with COPD with different blood eosinophil on admission and those without COPD and the prognosis of COVID-19. METHOD:A territory-wide retrospective study was conducted to investigate the association between elderly COPD patients with different blood eosinophil on admission and the prognosis of COVID-19. Elderly patients admitted to public hospitals and community treatment facility in Hong Kong for COVID-19 from January 23, 2020, to September 31, 2021, were included in the study. Severe diseases were defined as those who develop respiratory complications, systemic complications and death. RESULTS:Among the 1925 patients included, 133 had COPD. Forty had admission blood eosinophil count ≥ 150 cells/μL, and 93 had blood eosinophil count < 150 cells/μL. Patients with COPD and admission blood eosinophil count ≥ 150 cells/μL, but not those with admission blood eosinophil count < 150 cells/μL, had severe COVID-19 with the development of respiratory and systemic complications. They were more likely to develop respiratory failure (OR = 5.235, 95% CI = 2.088-13.122, p < 0.001) and require invasive mechanical ventilation (OR = 2.433, 95% CI = 1.022-5.791, p = 0.045) and intensive care unit admission (OR = 2.214, 95% CI = 1.004-4.881, p = 0.049). DISCUSSION:Our study suggested that the blood eosinophil count on admission could have significant prognostic implications among elderly patients with COPD. Patients with COPD and admission blood eosinophil count ≥ 150 cells/μL, but not those with admission blood eosinophil count < 150 cells/μL, have significantly increased risks of developing respiratory and systemic complications from COVID-19, when compared with non-COPD patients.

BACKGROUND:Inducing T cell responses by vaccines among elderly has been a long-standing challenge. There is a need for effective COVID-19 vaccines to boost waning immunity against emerging SARS-CoV-2 variants, especially for the elderly. This study investigated the safety and immunogenicity of a PD-1-enhanced COVID-19 DNA vaccine (ICCOV™), as a booster vaccine in healthy adults (aged 18-59 years) and elderly (aged 60-75 years). METHODS:This open-label, non-randomised Phase 2 study enrolled healthy participants aged 18-75 years who had previously been vaccinated with Sinovac CoronaVac, Pfizer-bioNTech Comirnaty vaccines, or both. Participants were stratified into four cohorts according to age, primary vaccination, and COVID-19 infection history, namely Adult-CoronaVac, Adult-Comirnaty, Adult-Mixed, and Elderly-Mixed cohorts. Participants were administered with a single dose of 2 mg ICCOV intramuscularly followed by electroporation using the proprietary TERESA-EPT-I device. Participants were followed up for 60 days. The primary endpoint was T cell immunogenicity within 28 days post-ICCOV vaccination. The secondary endpoints were safety, T cell and antibody responses within 60 days post-vaccination (ClinicalTrials.govNCT05904054). FINDINGS:The study was conducted at Gleneagles Hospital Hong Kong between 30 June and 30 November 2023. In total, 31 participants were enrolled across the Adult-Comirnaty (n = 4), Adult-Mixed (n = 15), and Elderly-Mixed (n = 12) cohorts. All enrolled participants completed the study and were included in safety and immunogenicity analyses. Among these participants, 2 from the Adult-Comirnaty cohort, 9 from the Adult-Mixed cohort, and 4 from the Elderly-Mixed cohort reported a total of 31 adverse events, all in grade 1-2. Pain at the administration site was the most frequently reported (38·7%). The proportion of participants demonstrating an increase of SARS-CoV-2-specific ELISpot T cell responses within 28 days post ICCOV vaccination was 100% (4/4), 80% (12/15), and 75% (9/12) in Adult-Comirnaty, Adult-Mixed, and Elderly-Mixed cohorts, respectively. Single ICCOV vaccination elicited SARS-CoV-2-specific, polyfunctional CD8+ and CD4+ T cells against both ancestral and Omicron strains in all cohorts. The magnitude of responses was not inferior in the elderly, compared to adults. No elevation of antibody responses was detected. INTERPRETATION:Single PD-1-enhanced ICCOV booster DNA vaccination did not show major safety concerns. The ICCOV booster elicited cross-reactive T cell responses to multiple SARS-CoV-2 strains, including in the elderly. This report demonstrates the T-cell boosting immunogenicity of ICCOV in the susceptible elderly population. FUNDING:Clinical Translational Catalyst, Hong Kong Science & Technology Parks Corporation.

BACKGROUND:Influenza surveillance and drug resistance testing have always been central to clinical efforts. Therefore, researching the virus characteristics and antiviral drugs is essential. METHOD:The HA and NA activities were assessed in influenza strains, and mutations were identified through gene sequencing. The effects of oseltamivir, molnupiravir, and baloxavir treatments were evaluated in vitro. The effectiveness of molnupiravir monotherapy and its combination with baloxavir was also evaluated in a mouse model. Changes in body weight and lung tissue were examined, including pathological changes, virus replication, and inflammation levels. RESULTS:Forty-one seasonal influenza H1N1 strains from 2023 were used. The EC50 of oseltamivir was significantly increased compared to the 2009 reference strain. Correlation analysis showed that the increase in EC50 was related to the HA and NA activities. The antiviral effects of molnupiravir and baloxavir significantly inhibited virus replication; the combination treatment of molnupiravir/baloxavir showed more potent and synergistic inhibitory effects in vitro. In the mouse model, molnupiravir treatment effectively inhibited virus replication and lung inflammation, but the treatment did not improve weight loss or reduce mortality. With the molnupiravir/baloxavir treatment, viral replication was significantly inhibited and proved to be more effective than either monotherapy. The combination therapy also showed the lowest inflammatory response along with a higher survival rate. CONCLUSIONS:The increase in HA and NA activities of seasonal influenza reduced the efficacy of oseltamivir treatment, but the effectiveness of molnupiravir and baloxavir was retained. Combination therapy showed a significant antiviral effect, which provides a reference for the clinical treatment.

INTRODUCTION:Neutropenic fever (NF) has a crude mortality rate of 3-18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone. METHODS AND ANALYSIS:This pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients' blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay. ETHICS AND DISSEMINATION:The institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing. TRIAL REGISTRATION NUMBER:NCT06794320.

BACKGROUND:Kaposi sarcoma herpesvirus-inflammatory cytokine syndrome (KICS) is a rare, life-threatening condition associated with Kaposi sarcoma and systemic immune dysregulation induced by Human Herpesvirus 8 (HHV-8). With a mortality rate approaching 60%1 (Goncalves, Ziegelbauer, Uldrick, Yarchoan in Curr Opin HIV AIDS 12(1):47-56, 2017), KICS poses significant diagnostic and therapeutic challenges. This report examines a case of KICS in a patient with well-controlled HIV, emphasising the clinical complexities, treatment strategies, and the need for heightened awareness. CASE PRESENTATION:A 59-year-old British male with a controlled HIV infection on Bictegravir/Emtricitabine/Tenofovir alafenamide presented with fever, malaise, lymphadenopathy, splenomegaly, and a purplish plantar plaque. Laboratory findings included anaemia, thrombocytopenia, hypoalbuminemia, hyponatremia, elevated inflammatory markers, and a high HHV-8 level. Diagnosis of HHV-8 positive lymph nodes and Kaposi sarcoma on the plantar aspect was confirmed. The patient was treated with Foscarnet, steroid, Rituximab, Tocilizumab, intravenous immunoglobulin (IVIG), and Paclitaxel, reducing viral load and improving cell count. This case highlights the complexities of managing Kaposi sarcoma within the realm of immune complex syndrome. CONCLUSIONS:Our case report underscores the critical need for heightened awareness and recognition of KICS, given its rarity and unique clinical characteristics. By elucidating the complex interrelationships between Kaposi sarcoma, inflammatory cytokines, and immune dysregulation, we aim to contribute to the existing knowledge base and facilitate improved diagnosis, management, and therapeutic interventions for this challenging syndrome. Further research is warranted to explore novel treatment modalities and unravel the underlying mechanisms driving KICS.

Background/Objectives: Vaccination is a key preventive measure against pneumococcal disease, but uptake rates remain low in high-risk populations. Limited information exists on pneumococcal vaccine uptake in individuals with a history of pneumococcal disease. This study aims to assess pneumococcal vaccine uptake and the factors associated with it in patients hospitalized for pneumococcal disease, before and after hospitalization, across time periods before, during, and after the COVID-19 pandemic. Methods: Data for patients aged ≥18 years who were hospitalized for pneumococcal disease between 2015 and 2024 were extracted from the Hospital Authority’s territory-wide electronic medical record database. The uptake of pneumococcal vaccines in subgroups aged 18–64 years and ≥65 years, with and without risk conditions, both before and after hospitalization for pneumococcal disease, was assessed, followed by multivariate analyses of the factors associated with vaccination uptake by logistic regression models. Results: This study included 5517 patients hospitalized for pneumococcal disease. Prior to hospitalization, the vaccination uptake among the eligible patients was 20.5%, with only 8.1% fully vaccinated, despite the majority (87.9%) having previous hospitalizations (subgroup medians 3–9 times) or outpatient clinic visits (subgroup median 61–107 times). After discharge, during a median follow-up of 1.85 years, almost all the eligible patients (98.4%) received subsequent inpatient (subgroup medians 3–4 times) and outpatient (subgroup medians 21–28 times) care, but only 32.2% of the eligible patients received the vaccine. Factors associated with increased vaccine uptake post-discharge included age ≥75 years (OR 1.6), ≥10 subsequent hospitalizations (OR 2.1), and ≥10 subsequent clinic visits (OR 55.9). Vaccination rates within 12 months post-discharge were significantly lower in the patients hospitalized during the COVID-19 pandemic (3.5%) compared to the baseline (11.6%) and post-COVID-19 (6.6%) periods. Conclusions: The uptake of the pneumococcal vaccine before hospitalization for pneumococcal disease was low and continued to be suboptimal post-discharge. Numerous vaccination opportunities were missed in both the inpatient and outpatient settings. These findings indicate a need to improve vaccination strategies.