Influenza and Other Respiratory Viruses

Background The COVID-19 pandemic substantially altered respiratory pathogen circulation worldwide. However, longitudinal analyses of changes in respiratory pathogen ecology across the pandemic and post-pandemic periods remain limited. Methods We analyzed 19,968 respiratory samples tested with the BioFire(R) FilmArray(R) Respiratory Panel at a hospital in Tokyo, Japan, between January 2020 and March 2026. We evaluated temporal changes in pathogen circulation, age-specific epidemiology, co-detection patterns, pairwise pathogen associations, and clinical parameters. Results At least one respiratory pathogen was detected in 27.8% of tests. Respiratory pathogens resurged asynchronously following the relaxation of COVID-19-related public health measures. Influenza virus circulation remained markedly suppressed until late 2022 before re-emerging in successive large seasonal epidemics, whereas other pathogens, including RSV, human metapneumovirus, and Mycoplasma pneumoniae, exhibited distinct resurgence patterns. Pathogen distributions also varied by age. Human rhinovirus/enterovirus remained predominant among young children, whereas SARS-CoV-2 predominated among older adults. Co-detection occurred in 14.0% of positive specimens and was significantly more frequent in younger patients. Pairwise analysis identified both positive and negative pathogen associations; however, the patterns varied across age groups and study periods. Conclusions Respiratory pathogen circulation changed substantially during the transition from the COVID-19 pandemic to the post-pandemic period, with pathogen-specific, age- and period-dependent patterns. Continued surveillance is warranted to determine how respiratory pathogen circulation will evolve and to inform infection control strategies in the post-pandemic era.

Background: Influenza vaccine effectiveness (VE) is assessed annually through prospective enrollment of patients presenting with acute respiratory symptoms in a test-negative study design. Influenza VE has also been estimated from electronic health record (EHR) databases by linking medical diagnoses, laboratory test results, and patient influenza vaccination. There are limited data on agreement between influenza VE estimates from prospective enrollment versus EHR databases. Methods: The US Influenza Vaccine Effectiveness Network prospectively enrolled outpatients meeting clinical screening criteria and collected respiratory specimens to determine influenza virus infection. Seven study sites also identified EHR databases that included diagnostic codes for outpatient encounters associated with medically attended acute respiratory illness (MAARI), clinical respiratory virus testing, and influenza vaccination status. Effectiveness of influenza vaccination against laboratory-confirmed influenza was estimated from both data sources using logistic regression models including patient age, study site, and month of illness as 100(%) x (1 - adjusted odds ratio), comparing influenza vaccination among laboratory-confirmed influenza-positive patients versus laboratory-confirmed influenza-negative patients. Results: From October 2024--April 2025, 2,016 (30%) of 6,793 prospectively enrolled patients and 75,885 (24%) of 282,444 EHR MAARI encounters had laboratory-confirmed influenza virus infection. Effectiveness of vaccination against laboratory-confirmed influenza was 36% (95% confidence interval [CI]: 26-44) among prospectively enrolled patients and 38% (95% CI: 36-39) among EHR MAARI encounters. Comparing influenza VE estimates from the two data sources, confidence intervals overlapped for all age groups except for adults aged [≥]65 years: -3% (95% CI: -53-30) among prospective enrollment versus 35% (95% CI: 32-39) VE from EHR MAARI encounters. Conclusion: Overall, influenza VE estimates from retrospective EHR data were similar to VE estimates using the test-negative design with prospective enrollment. The age group-specific differences in estimated VE observed in US adults aged [≥]65 years compared with younger age groups merit further investigation.

The increasing incidence of H5N1 influenza virus transmission from animal species to humans has heightened concerns about an imminent H5N1 pandemic. Prior studies using recombinant hemagglutinin and neuraminidase proteins have reported age-dependent cross-reactivity to H5N1, attributed to immune imprinting from an individual's first influenza virus exposure. However, whether this pattern holds when using whole inactivated virus (WIV), capturing antibodies against diverse viral proteins, and is stable over time remains unknown. We therefore aimed to determine whether H5N1 cross-reactivity of pre-existing antibodies to whole virus follows an age-dependent or imprinting-specific pattern, and whether this pattern is stable over a five-year period. To this end, we measured serum antibody levels in adolescents, adults and seniors by ELISA using whole inactivated H5N1 virus as antigen rather than purified proteins. Detectable, albeit generally low, levels of H5N1-reactive antibodies were present in most individuals, irrespective of age. Comparison of antibody levels against H5N1 with those to five historical influenza virus strains revealed a consistent positive correlation between H5N1-reactive antibodies and responses to the H1N1pdm09 strain A/California/7/2009 (CA), across all age groups. Using unbiased clustering of antibody titers against H5N1, CA, and the H3N2 strain A/Perth/16/2009 (PE), we identified seven distinct age-transcending antibody profiles. These profiles covered individuals with varying titers to all three included viruses but also identified individuals with high anti-CA levels, yet low anti-H5N1 levels and vice versa. Moreover, despite stable antibody levels over a five-year interval in the study population, individual antibody levels and profiles fluctuated considerably over this period. Taken together, our results confirm the presence of H5N1-reactive antibodies in human sera and their association with previously circulating strains. However, they also caution against inferring antibody levels against a new strain based solely on responses to antigenically related strains and highlight the limitations of extrapolating immune status from single timepoint measurements.

Since the U.S. 2013/14 influenza season, the CDC's FluSight Challenge has provided a platform for evaluating influenza forecasting models and fostering collaboration across institutions. The Challenge aims to improve the science and enhance the utility of infectious disease forecasts for public health decision making. We analyzed ten years of submitted forecasts (2014/15-2019/20 (influenza-like illness seasons) and 2021/22-2024/25 (hospital admissions seasons)) across a range of model types, including statistical, mechanistic, machine learning, and hybrid models. Influenza-like illness (ILI) forecasts were evaluated using the exponentiated logarithmic score (skill metric) while hospital admissions forecasts were evaluated using the log transformed relative Weighted Interval Score. Corresponding potential performance differences were assessed using Wilcoxon rank-sum tests, and associations with team participation history were evaluated using Spearman's rank correlation. Model performance varied by season, and no single model type consistently outperformed others. In ILI seasons, statistical models generally performed better than mechanistic and machine learning models, though consistent differences were not observed in more recent hospital admissions seasons. Ensemble forecasts showed better overall performance across seasons, and the CDC's FluSight ensemble ranked among the top-performing forecasts every year. We also found a positive correlation between forecast accuracy and the number of years a team participated in the Challenge, with statistically significant associations in four seasons. These findings highlight the benefits of ensemble approaches and sustained engagement in improving forecasting performance, while also underscoring the continued value of forecast evaluation before and following the COVID-19 pandemic. Insights from the FluSight Challenge can guide future infectious disease forecasting efforts and support more effective public health preparedness.

During the 2025-26 respiratory virus season, changes to COVID-19 vaccine eligibility, recommendations, and communication may have made vaccination follow-through especially challenging. Under-vaccination may reflect not only lack of willingness, but also breakdowns between willingness and uptake. We analyzed data from 3,390 adults in the CHASING COVID Cohort who completed assessments in August 2025 and March 2026 to examine gaps between vaccine willingness and subsequent influenza and COVID-19 vaccination. Vaccine willingness was defined using prior-season vaccination and stated intention to vaccinate during the 2025-26 respiratory virus season. In August 2025, 73% of participants were influenza vaccine willing and 68% were COVID-19 vaccine willing. Among vaccine-willing participants, 17% and 39% were unvaccinated for influenza and COVID-19, respectively, by March 2026. Absence of prior-season vaccination was the strongest predictor of not vaccinating for influenza and COVID-19, respectively (aRR [95% CI]: 4.04 [3.44-4.74]; 3.01 [2.72-3.34]). Non-vaccination was also associated with food insecurity (1.99 [1.66-2.37]; 1.47 [1.33-1.63]), any healthcare barrier (1.89 [1.57-2.28]; 1.51 [1.36-1.67]), and being not at all confident in vaccine safety (2.95 [2.15-4.05]; 2.21 [1.88-2.59]). Trajectory analyses suggested willingness-uptake gaps reflected incomplete follow-through on intentions and discontinuation among some prior vaccinators. Commonly reported reasons among vaccine-willing non-vaccinators included difficulty finding a convenient time, place, or appointment and, for COVID-19, lack of healthcare provider recommendation. Findings among non-vaccinated adults with prior or stated openness to vaccinate highlight missed opportunities and suggest avenues to improve coverage through strategies that reinforce vaccine confidence, reduce access and logistical barriers, and make vaccination easier to complete.

Introduction: RSV vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least 2 RSV seasons following vaccination. No data have been published on real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination. This study evaluates bivalent RSVpreF VE against RSV-related lower respiratory tract disease (LRTD) hospitalizations/ED visits throughout 3 seasons after vaccination. Methods: This retrospective test-negative case-control evaluates bivalent RSVpreF VE among adults aged >/= 60 years at Kaiser Permanente Southern California with LRTD over 3 RSV seasons (11/24/20230-4/18/2026). Cases were RSV-positive without coinfection. Controls were negative for RSV, hMPV, influenza, SARS-CoV-2, and positive for a non-vaccine preventable disease pathogen. Exposure was bivalent RSVpreF (Abrysvo) receipt >/= 21 days before LRTD. Adjusted VE was estimated using odds ratios from multivariable logistic regression or generalized estimating equations. Results: Overall, adjusted VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI:68-87), 70% (95% CI:53-81), and 51% (95% CI:-12-78) in the first, second, and third season after vaccination, respectively. Among non-immunocompromised individuals, adjusted VE against RSV-related LRTD was 87% (95% CI:75-94), 76% (95% CI:55-87), and 58% (95% CI:-21-86) in the first, second, and third season after vaccination, respectively. Adjusted VE across the 3 combined seasons was 73% (95% CI: 64-80) overall and 80% (95% CI: 69-87) among non-immunocompromised individuals. Conclusion: These results suggest Bivalent RSVpreF provides protection against RSV-related LRTD outcomes for at least three seasons after vaccination in this population of older adults with a prevalence of comorbidities. This suggests RSV vaccination results in substantial individual and public health benefit.

MotivationInfluenza is an infectious disease associated with excess human deaths. For influenza A virus (IAV), the surface antigens hemagglutinin (HA) and neuraminidase (NA) define the specific subtype. The high mutation rate of IAV can make clinical testing and assigning subtype after sequencing challenging. Accurate subtype classification is important for tracking circulating IAV strains that may impact human health. ResultsWe analyzed a large IAV protein sequence dataset with known HA and NA subtypes. Using logistic regression and random forest approaches, we identified a small set of subtype-associated amino acids, which were then used to develop a subtype characterization method with near-optimal accuracy. Further analysis indicated that signal sequence peptide variation and indels in HA and NA explained the unique combination of subtype-associated amino acids.

Human metapneumovirus (HMPV) and human parainfluenza viruses (HPIV 1-4) are common causes of seasonal respiratory illness, but their household transmission dynamics remain poorly defined. We analyzed weekly symptom data and nasal swabs from a prospective household surveillance study in Washington and Oregon from June 2022 to March 2024. Swabs were tested for HMPV and HPIV, and a subset underwent whole-genome sequencing. Distinct index cases occurred in 236 (23%) and 341 (36%) of 1,040 households for HMPV and HPIV, respectively. Household secondary attack rates (SAR) and median generation times were similar for HMPV (8.7%, 7 days) and HPIV (7.3%, 7 days). Sequenced samples reflected contemporaneous circulating strains during the same period, with household sequences clustering closely together. High-quality viral whole genome sequences were recovered for two or more individuals within a household in a total of 26 households for HMPV and 45 households for HPIV. Intra-household pairwise nucleotide (nt) distance ranged from 0 to 14 nt (median 0) for HMPV and 0-8 nt (median 1) for HPIV when cases occurred 0-15 days apart. Transmission occurred primarily from children to adults, emphasizing the importance of childcare- and school-associated spread and supporting child-focused prevention strategies to reduce household transmission.

Background Nirsevimab has been widely administered in the United States since 2023 to protect infants and young children from severe disease caused by respiratory syncytial virus (RSV). Although early post-licensure studies have shown high effectiveness against medically attended RSV infection, uncertainty remains about the durability of protection, effectiveness beyond the first RSV season, and the extent to which changing RSV seasonality influences real-world effectiveness. Objective To estimate the effectiveness of nirsevimab against medically attended RSV infection across three consecutive RSV seasons and to examine how effectiveness varies by season and time since immunization. Methods We conducted a test-negative case-control study utilizing electronic health records of infants and young children tested for RSV by polymerase chain reaction in outpatient and inpatient settings within the Yale New Haven Health System between October 1, 2023, and March 1, 2026. Effectiveness of nirsevimab was estimated using multivariable logistic regression, adjusting for age, weekly RSV activity, pre-existing risk factors, and other potential confounders. Variation in effectiveness was examined by season, encounter setting, and time since immunization up to 24 months. Results Overall, 17,755 infants and young children were tested for RSV infection, of whom 2,388 (13.4%) were cases and 15,367 (86.6%) were controls. The overall effectiveness of nirsevimab was 67.3% (95% confidence interval [CI]: 59.8, 73.3%) against all medically-attended RSV infections, 60.2% (95% CI: 49.6, 68.5%) against RSV-associated outpatient visits, and 88.9% (95% CI: 82.3, 93.0%) against RSV-associated hospitalization. Effectiveness against medically attended RSV infection declined across seasons, from 76.7% (95% CI: 60.5, 86.3%) in 2023/24 to 54.4% (95% CI: 33.0, 68.9%) in 2025/26. Lower season-specific effectiveness in later seasons corresponded with progressively delayed RSV activity over. Protection against RSV-associated hospitalization declined with increasing time since immunization, from 92.5% (95% credible interval [CrI]: 85.9, 96.4%) at 1 month, to 77.2% (95% CrI: 60.4, 87.6%) at 6 months, and 39.9% (95% CrI: 2.4, 63.3%) at 12 months post-immunization, after which effectiveness plateaued. Conclusions Nirsevimab remained effective against RSV-associated hospitalization through 6 to 12 months after immunization. Delayed RSV activity was associated with lower effectiveness, highlighting the importance of aligning administration with local RSV circulation.

Background Pediatric immunizations for Respiratory Syncytial Virus (RSV), including monoclonal antibodies for infants and vaccines for pregnant people, have become broadly available and can prevent severe RSV outcomes in infants. However, quantifying the impact of RSV immunization in prevention of severe pediatric illness at the population-level is limited by lack of RSV case surveillance data. The Massachusetts Department of Public Health (DPH) conducted a modeling analysis using routine public health surveillance data to estimate the state-level impact of new RSV immunization products on Emergency Department (ED) visits and hospitalizations in Massachusetts for highest risk pediatric groups. Methods A scenario projection tool, called R.Scenario.Vax, was utilized to simulate RSV-associated ED hospital encounters by age group in the context of newly available immunizations. ED visit and hospitalization data from the National Syndromic Surveillance Program (NSSP) during the time period 10/08/2017--10/19/2024 were analyzed, scaled to account for changes in RSV testing practices over time and missing encounter volume in historic data, and utilized to inform model fit of a "typical" RSV season. RSV immunization data from the Massachusetts Immunization Information System (MIIS) for the 2023--2024 and 2024--2025 RSV seasons informed high and moderate pediatric RSV immunization coverage scenarios and their impact was compared to a counterfactual reference scenario of no new immunizations. Median projections were quantitatively and qualitatively compared to observed 2024--2025 season data. Percent reduction in hospital encounters and encounters averted per 10,000 population were calculated for each scenario as compared to the reference. Results Projections for the youngest at-risk age groups showed significantly lower RSV-associated ED visits and hospitalizations during the 2024--2025 season for both high and moderate immunization coverage scenarios. Median projections for infants under 6 months old in the highest coverage scenario, wherein nearly all infants were immunized, showed 72.6% lower ED visits and 73.4% lower hospitalizations when compared to the reference scenario, equating to 262 ED visits and 85 hospitalizations averted per 10,000 population. Conclusions Our results support the use of modeling methods for public health insights and suggest that RSV immunizations for infant populations result in significantly lower RSV-related ED encounters in Massachusetts.

Background Severe acute respiratory infections (SARI) strain healthcare systems. Sentinel surveillance remains central to SARI monitoring, but routinely collected hospital discharge data offer a scalable, population-wide complement. In Finland, national registers now enable register-based surveillance, yet SARI case definitions remain unevaluated. Aim To evaluate whether routinely collected electronic health records can support register-based SARI surveillance and establish a national case definition. Methods We conducted a retrospective register-based study linking inpatient discharge data from the Finnish Care Register for Health Care (Hilmo) and laboratory-confirmed pathogen notifications from the National Infectious Diseases Register (NIDR). Admissions were aggregated into hospitalisation episodes using generic and pathogen-specific respiratory ICD-10 codes and linked to laboratory-confirmed respiratory pathogens within an admission-centred window. We assessed the impact of diagnostic coding position, laboratory linkage windows and alternative case definitions on age distribution, seasonality and epidemic trend detection. Results We included 145,435 respiratory hospitalisation episodes. Laboratory confirmations clustered around admission, and a -7-to-+3-day window was selected; 51,498 (35.4%) had a linked laboratory confirmation. Specific primary-position diagnoses preserved clear seasonality and age distributions consistent with SARI epidemiology, whereas secondary-position diagnoses showed attenuated seasonality. A combined case definition incorporating specific primary diagnoses and laboratory-supported syndromic episodes produced stable epidemic curves while improving sensitivity over laboratory confirmation alone. Conclusion National discharge and laboratory registers can support robust SARI surveillance in Finland when case definitions are carefully designed. A combined register-based definition balances specificity, sensitivity and feasibility, complementing sentinel surveillance and integrated respiratory monitoring. Keywords Severe acute respiratory infection (SARI); surveillance; electronic health records; ICD-10; case definition; Finland

Accurate outbreak forecasts are critical for timely and effective public health response. In the United States, however, most forecasts are produced at the state level, which can mask substantial sub-state heterogeneity and limit their utility for local planning. We generated and evaluated forecasts of the percentage of Emergency Department visits attributable to influenza across 173 large metropolitan Health Service Areas (HSAs) using a gradient boosting quantile regression (GBQR) model, and compared their accuracy to forecasts derived from state-level data alone. At a one-week, two-week and three-week horizon, local forecasts outperformed state-based forecasts in 98.8%, 90.8%, and 78.6% of HSAs, respectively, achieving mean weighted interval scores that were on average a 39.2% lower (95% range: 5.9% to 76.7%), 19.6% lower (-6.3% to 59.5%) , and 11.4% lower (-11.7% to 44.9%), respectively. The performance advantage of local forecasting was strongest in HSAs representing a smaller share of their state's population and increased with the proportion of the HSA population living in urban areas and the number of metropolitan areas within a state. These results, based on an analysis of HSAs with populations greater than 250,000, demonstrate that fine-scale modeling can substantially improve forecast accuracy and highlight the potential value of local forecasts for outbreak preparedness and response.

Highly pathogenic avian influenza A(H5N1) virus continues to expand globally across wild birds, poultry, and multiple mammalian hosts, and the detection of genetic features associated with mammalian adaptation underscores the need to better define preexisting human immunity relevant to pandemic preparedness. Although serologic and vaccine studies have historically emphasized hemagglutinin (HA), neuraminidase (NA) is a key antigen capable of providing protective immunity. Here, we performed a retrospective analysis of NA-specific antibodies in human sera collected across ten influenza seasons spanning the pre- and post-2009 pandemic periods. A total of 749 paired human serum samples (1,498 total) were obtained prior to seasonal inactivated influenza vaccination (T1) and 28 days after vaccination (T2). NA-inhibiting antibodies were measured by enzyme-linked lectin assay (ELLA) using N1 antigens representing three genotypes (B.3.13, D1.1, and EA-2021-AB) from clade 2.3.4.4b A(H5N1) viruses. In parallel, HA-directed responses were assessed by hemagglutination inhibition (HAI). In addition, luciferase-based microneutralization assays were performed to assess the presence of neutralizing antibodies. NA-inhibiting antibodies were detectable against all three genotypes across seasons. Seasonal vaccination was associated with a modest but reproducible increase in NA-inhibiting titers, most apparent from the 2009-2010 season onward, coincident with the introduction of A(H1N1)pdm09 into seasonal vaccine formulations. In contrast, HAI activity against H5 was generally low or undetectable, despite detectable HA-reactive antibodies by ELISA. These data indicate that cross-reactive NA-specific antibodies are present in human sera and can be boosted by seasonal vaccination, supporting increased consideration of NA in influenza serosurveillance and vaccine evaluation. IMPORTANCEThe continued spread of A(H5N1) viruses and reports of mammalian adaptation markers heighten concerns about potential zoonotic transmission into humans. Most studies of human antibody responses focus on influenza HA, but NA is also an important immune target. By analyzing paired sera from humans collected over ten influenza seasons, we show that NA-inhibiting antibodies cross-reacting with multiple contemporary genotypes from clade 2.3.4.4b A(H5N1) viruses are detectable and can be modestly boosted seasonal inactivated influenza vaccination, particularly after the 2009 pandemic. These findings highlight the importance of inducing NA-specific antibodies during influenza vaccination and in including NA in surveillance and in the assessment of vaccines intended to improve preparedness for emerging influenza viruses.

In fall of 2025, a fatal infection of highly pathogenic avian influenza (HPAI) virus H5N5 occurred. To define the risk of this emerging virus to humans, we performed a comprehensive analysis based on our established triage. Serological analysis revealed that humans across all birth years had no detectable neutralizing antibodies to this H5N5 isolate. Further characterization revealed a lack of phenotypic signatures associated with epidemiologically successful influenza viruses in humans, including reduced replication in human airway cells and an avian-like pH of inactivation. Additionally, assessment of H5N5 in ferrets revealed a lack of direct contact transmission and moderate disease severity. H5N5 infection in ferrets with prior immunity against the 2009 H1N1 pandemic strain resulted in fewer clinical signs and reduced viral shedding. Together our data suggest that the current H5N5 HPAI lineage poses a low pandemic risk. ImportanceHPAI H5N5 viruses have caused widespread infection and death in avian species, and characterizing their pandemic risk traits is critical to understanding the threat posed to humans. In this work we analyzed an isolate that resulted in a human fatality in 2025. We found that this strain lacks many key features of influenza viruses with epidemiological success in humans including reduced growth in human lung cultures, a pH of inactivation less than 5.0, and lack of transmission to cohoused recipient ferrets. Prior immunity with seasonal H1N1 strain also reduced the viral load and disease burden of the virus. Taken together, these data suggest that currently circulating H5N5 poses a low risk to humans but highlights the importance of phenotypic characterizations for future risk assessments as the virus evolves in wild birds.

Introduction: Respiratory infections are a leading cause of morbidity. Newly available vaccines to prevent respiratory syncytial virus (RSV) disease and encouraging clinical progress on vaccines for human metapneumovirus (hMPV) and parainfluenza (PIV) could reduce the disease burden beyond existing influenza and SARS-CoV-2 immunisation programs. However, evidence on the contribution of these viruses to respiratory disease burden across the lifespan remains limited. Methods: We reviewed studies from 01/2002-11/2025 reporting age-stratified, medically attended cases of influenza, and at least one of RSV, hMPV, or PIV, in high-income countries, excluding periods substantially overlapping with the COVID-19 pandemic. Using only studies that tested for all four viruses, we estimated the age-specific proportion of cases that were non-influenza (total across RSV, hMPV and PIV) compared to influenza using a mixed-effects logistic regression model. Results: Following exclusions and screening, 61 studies were included in the primary analysis comprising >500,000 detections of the four viruses. We found that a substantial proportion of medically attended respiratory illness in infants and young children was due to PIV, hMPV and RSV, rather than influenza, with a non-influenza virus proportion of 90.2% (95% CI 85.9-93.2%) in young infants aged 0-6 months. The converse was true for school-aged children, with a non-influenza virus proportion of 34.8% (95% CI 26.5-44.2%) in children aged 5-18 years. In adults aged 65+ years, non-influenza causes of medically attended disease were common at 60.2% (95% CI 50.0-69.5%). Restricting to studies reporting hospitalised cases (n=19) produced broadly similar age-specific trends in relative virus burden contributions. Discussion: We highlight the significant burden of medically attended illness due to PIV, hMPV and RSV across ages, particularly in infant and preschool-aged children and older adults, supporting the need for effective vaccines targeting this burden.

Seasonal influenza remains a major cause of morbidity and mortality worldwide. Although neuraminidase inhibitors improve outcomes, influenza-related deaths persist. We evaluated the impact of early aspirin (ASA) and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use on outcomes in adults hospitalized with influenza. This retrospective study included adults admitted to the University of Minnesota Medical Center from 2016 to 2018. Continuous variables were summarized as medians with interquartile ranges (IQRs) and categorical variables as counts and percentages. Group comparisons used Wilcoxon rank-sum, Chi-square, or Fishers exact tests. Analyses included case-control comparisons, assessments by vaccination status, and subgroup analyses by early ASA or NSAID use. Among 2,816 patients, 320 had laboratory-confirmed influenza, with vaccination less common among cases. Unvaccinated patients had higher rates of intensive care unit (ICU) admission (23.6% vs. 11.1%; P = 0.003) and ventilatory support (15.0% vs. 6.1%; P = 0.009). In vaccinated patients, early ASA use was associated with older age and higher in-hospital mortality, whereas early NSAID use was associated with no in-hospital deaths, better one- and three-year survival (P < 0.001), and fewer, though not statistically significant, cardiovascular complications. In unvaccinated patients, ASA use was associated with lower three-year survival (59.1% vs. 79.2%; P = 0.013), while NSAID use was associated with fewer ICU admissions and no cardiovascular or renal complications. In both vaccinated and unvaccinated adults hospitalized with influenza, early NSAID use was associated with improved survival and fewer complications, whereas ASA use was associated with worse outcomes.

Seasonal Influenza and COVID-19 vaccination programmes are critical for reducing morbidity and mortality in older adults, yet uptake remains uneven across populations. We aimed to profile vaccination attitudes and examine predictors of COVID-19/influenza vaccination uptake among a UK participatory surveillance system - FluSurvey. We analysed FluSurvey data from participants aged [&ge;]65 years who were eligible for both vaccines in the 2023-2024 and 2024-2025 Autumn - Winter seasonal campaigns. Descriptive analyses examined self-reported attitudes to influenza vaccination. Logistic regression examined factors (age, sex, socioeconomic status, education, employment, transport, smoking and chronic conditions) associated with influenza and COVID-19 vaccination uptake in each season, adjusting for confounders. Belonging to a risk group and reducing risk of influenza were frequently reported motivations for influenza vaccination, while building natural immunity and concerns around safety and adverse effects were frequently reported barriers. Individuals vaccinated against COVID-19 were more likely to receive an influenza vaccination (aOR2023-2024=13.90 [9.28-21.17]; aOR2024-2025=8.54 [5.82-12.60]), and vice-versa (aOR2023-2024=13.91 [9.30-21.19]; aOR2024-2025=8.52 [5.81-12.58]). Lower educational attainment was associated with lower odds of COVID-19 vaccination (aOR2023-2024=0.59 [0.45-0.78], aOR2024-2025: 0.56 [0.39-0.79]). Other results were weaker or demonstrated variation by season. Our findings highlight recent attitudes and barriers to influenza and COVID-19 vaccination among the FluSurvey cohort, which may inform approaches to improve vaccination coverage in the population.

Long COVID (LC) impacts quality of life, daily functioning, and healthcare utilization. Understanding the onset and duration of symptoms, characteristics of those at higher risk, and the barriers and facilitators for healthcare access and therapeutics are key to addressing this growing disease burden. In 2024 the Arizona CoVHORT, an ongoing 6-year longitudinal study, distributed a cross-sectional LC survey to gain additional in-depth information. Of 1,543 participants, 700 reported LC symptoms lasting 2-49 months. Following their first infection, LC+ participants had a 21% higher risk for a second infection and were 3.2 times more likely to report LC symptoms after that second infection compared to LC- participants. Significant factors associated with LC included female sex (OR=2.3), Hispanic ethnicity (OR=1.5), BMI>34.5 (OR= 1.7) and >2 infections (OR=3.2), while vaccination prior to first infection decreased the odds of reporting LC by 51% (R=0.49). Qualitative analyses detailed significant barriers to care and encounters with providers who lacked knowledge to test for or treat LC symptoms. With an estimated 400 million people impacted globally by LC, it is critical to gain in-depth information from patients to improve both access and quality of care, improve messaging, and target mitigation strategies to decrease the burden over time.

Importance: Maternal vaccination and long-acting monoclonal antibodies are now available in the U.S. to prevent RSV. Long-acting monoclonal antibody administration in the U.S. commonly occurs after hospital discharge in outpatient settings, leaving some infants unprotected early in life when severe RSV risk is highest. Comparative effectiveness between the two interventions and whether delays affect effectiveness estimates have not been quantified. Objective: To evaluate the effectiveness of infant long-acting monoclonal antibody strategies and a maternal vaccination strategy, each compared to no intervention, and the comparative effectiveness of intervention strategies when accounting for real-world delays in monoclonal antibody receipt. Design: Cohort study using target trial emulation to compare four strategies for prevention of RSV-related outcomes. Setting: The U.S. between 2023 and 2025 using a nationwide database of employer-sponsored commercial insurance claims. Participants: 120,586 commercially insured mother-infants, whose infants were born in the U.S. during the 2023-2024 or 2024-2025 RSV season. Infants who could not be paired with their mother's record, did not enroll in commercial insurance within 75 days from birth, received palivizumab, and had an implausible birth date were excluded. Interventions: Comparison of four RSV prevention strategies: (i) maternal RSVpreF; (ii) long-acting monoclonal antibody given within the first week of life (mAb as intended); (iii) long-acting monoclonal antibody given within a six-month grace period from birth (mAb within grace period); and (iv) a control. Main outcomes and measures: Effectiveness against first RSV-associated hospitalization and medically-attended RSV illness was summarized using adjusted hazard ratios (aHR) and estimated using an inverse propensity weighting approach, with weights accounting for maternal age, maternal comorbidities affecting pregnancy, obstetric and newborn complications, season, region, and birth timing relative to October 1. A weighted Kaplan Meier estimator was used to estimate strategy-specific cumulative incidence of RSV outcomes over time. Results: In the first five weeks of life, the mAb within grace period strategy doubled the hazard of RSV hospitalization (aHR: 2.0 [95% CI: 1.0-4.9]) and increased the hazard of medically-attended RSV (aHR: 1.6 [95% CI: 1.0-2.7]) compared to the maternal RSVpreF strategy. The hazard for RSV hospitalization was similar for the mAb as intended strategy compared to the maternal RSVpreF strategy (aHR = 0.9 [95% CI: 0.3-1.9]). Conclusions and relevance: RSVpreF and monoclonal antibodies were similarly effective when monoclonal antibodies were administered close to birth, but when accounting for real-world delays in monoclonal antibody receipt, the maternal RSVpreF strategy was more effective than the mAb within grace period strategy.

Clade 2.3.4.4b H5NX influenza viruses have spread widely in birds since 2020. In addition to causing disease in birds, these viruses have infected a variety of mammals, including humans. Clade 2.3.4.4b H5N1 viruses are currently causing an outbreak among dairy cattle in the United States, and it is important to determine if other mammals have been exposed to H5NX viruses. Cats, specifically outdoor and feral cats, frequently predate wild birds. Recent studies have shown that cats living on dairy cattle farms can be infected with H5N1. Here, we completed serological studies to determine if owned and feral cats living in an urban environment in the United States have evidence of past H5N1 exposures. We used multianalyte bead-based assays to measure clade 2.3.4.4b hemagglutinin (HA) antibody levels in serum samples collected in July 2023 to June 2025 from 417 feral and 228 owned cats from the greater Philadelphia area. We also measured antibody levels against a panel of HAs from other human and non-human influenza viruses, and the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We completed additional H5N1 and SARS-CoV-2 neutralization assays using samples that had detectable antibodies in the multianalyte bead-based assays. One cat (0.16%) was positive for H5 antibodies and twenty cats (3.1%) were positive for SARS-CoV-2 antibodies in both binding and neutralization assays. These data suggest that cats in the Philadelphia area have not been routinely exposed to clade 2.3.4.4b H5N1 viruses but have been more commonly exposed to SARS-CoV-2.