Influenza and Other Respiratory Viruses

Prior work has shown that school-age children's influenza activity precedes that of adults by one to two weeks. Whether this is robust across outcomes or constant across a season's course is unexamined. Using electronic health record data from two health systems in South Carolina (2016-2026) on individuals with an influenza diagnosis or positive test, we tested age-group lead-lag relationships across six measures using differenced cross-correlation and Granger causality, with significance confirmed via heteroskedasticity-robust block permutation. We tested whether relationships differed between a season's growth and decline phases. Children 5-17 years led every other age group by approximately one week in four out of six outcomes and were the only group showing any nonzero-lag relationship across 60 pairwise combinations. A screen of 150 source-target combinations identified 26 permutation-confirmed instances of children's lower-acuity activity preceding elevated emergency department or inpatient burden in other age groups. The same-outcome lead was concentrated during a season's growth phase, while the cross-severity lead was robust throughout both a season's growth and decline. School-age children's influenza activity is a robust, multi-outcome leading indicator with distinct transmission-timing and severity-progression signals in different phases of seasonal epidemics, supporting incorporation of age-stratified, phase-aware indicators into influenza forecasting.

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.

Respiratory syncytial virus infection is a common cause of hospitalizations in infants and elderly patients. With the increased availability of vaccines and therapeutic antibodies, surveilling the sequence landscape of viral genomes is important to increase awareness of potentially neutralizing mutations. During the 2023-24 and 2024-25 RSV seasons, we collected unpaired nasopharyngeal swab specimens from patients presenting to Arizona healthcare systems with symptoms of influenza-like illness. Using either tiled am-plicon-based enrichment or a commercial oligo hybrid-enrichment panel and next generation sequencing, we obtained genome sequences for RSV and co-infecting viruses. We performed phylogenetic and genomic analyses to classify RSV genomes and detect mutations in the antigenic sites of the F protein and conserved central domain of the G protein. Phylogenetic analysis showed RSV-A strains belonged to the A.D. 1, A.D.2, A.D.3, and A.D. 5 subclades. RSV-B genomes belonged to the B.D.4.1, B.D.4.1.1, B.D.E.1, B.D.E.5, and B.D.E. 7 clades. We found 9 polymorphic sites located in the antigenic sites of the F protein in our RSV-A genomes and 18 polymorphic sites in our RSV-B genomes over the two-season surveillance period. We identified 7 polymorphic sites in our RSV-A genomes and 8 polymorphic sites in our RSV-B genomes that are in the conserved central domain of the G protein. We also discovered 3 (6.7%) and 27 (15.8%) incidences of viral coinfections in the 2023-24 and 2024-25 seasons, respectively. Viral genomic surveil-lance plays an important role in maintaining the efficacy of vaccine and therapeutic agents. Continued monitoring of circulating variants is an important component of public health.

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.

Background FluSurvey is a participatory surveillance system, through which participants report weekly respiratory symptoms, healthcare use and social contacts. To support rapid public health assessment we developed a respiratory self-swabbing feature. We aimed to assess the feasibility of self-swabbing among symptomatic FluSurvey participants. Methods FluSurvey self-swabbing was deployed in England between January-March 2026. Adults reporting recent Acute Respiratory Infection symptoms were eligible for a self-swabbing Covid-19, RSV and Influenza PCR test which was returned to the laboratory by post. Participants were sent optional feedback surveys. We described swabbing interest, timeliness and participant demographics. We evaluated participant feedback to improve the process. Results There were 234 eligible illnesses during the study period; 45.7% (107/234) requested test kits and 93.5%(100/107) test kits were returned. Of these, 97.0%(97/100) had valid results; median participant age was 61.74 years (IQR:47.4-67.4), 68.4% were female and 90.0% were of white ethnicity. All nine regions in England were represented. Timeliness was high; the median time from symptom onset to specimen date was 4.0 days (IQR:3.0-5.0). Of participants completing feedback surveys, 96.7%(59/61) would consider participating in self-swabbing again. Conclusions We developed a tool to test individuals, often not presenting to healthcare, for respiratory viruses using an established community-based surveillance system. This tool can be rapidly deployed and adapted to public health need, to assess community-based emerging respiratory or pandemic infections. The high return rate and positive feedback suggest continued engagement of the cohort in respiratory virus swabbing.

Background: The relationship between recent viral infection and subsequent susceptibility to, or protection against, other viruses remains unclear, particularly across ages and symptom status. Methods: A prospective cohort study enrolled participants aged 6 months to 49 years in Washington and Oregon, USA, 2022-2024. Weekly nasal swabs were tested for SARS-CoV-2, respiratory syncytial virus (RSV), and influenza A/B; additional swabs were collected during symptomatic illness and were also tested for parainfluenza (PIV) 1-4, endemic human coronaviruses (hCOV), adenovirus, human metapneumovirus, human rhinovirus (hRV), and enteroviruses. Proportional hazards regression models were used to characterize associations between incident symptomatic infection (illness) and history of recent illness due to other viruses (within 1-7, 8-14, 15-30, 31-60, 61-90, 91-180 days), adjusted for geographic region, age, sex, daycare/school/work attendance, household size, and number of children in the household. For SARS-CoV-2, influenza, and RSV, these analyses were repeated to study incidence of infection (including asymptomatic cases). Findings: Of 3,560 participants, 2,969 (83%) had [≥]1 illness over 4,299 person-years. Adjusted hazard ratios (aHRs) in the short term ([≤]2 weeks) after an illness were predominantly below 1, indicating that recent viral illness was often associated with lower risk of subsequent illness with other viruses. Across age groups, recent hRV illness was associated with lower risk of hCOV, PIV, and RSV illness (aHRs 0.07-0.27). SARS-CoV-2 illness was associated with a higher short-term risk of adenovirus and PIV illness (aHRs 3.20-3.33). In children aged 6 months-4 years, recent influenza illness was associated with higher short-term risk of SARS-CoV-2 illness. Including asymptomatic infections generally attenuated these associations. Interpretation: Some viral illnesses may alter short-term susceptibility to subsequent viral illnesses. Interactions may differ by age and symptom status. Funding: US Centers for Disease Control and Prevention; Washington State Department of Health.

Background: Recombinant (RIV) and cell culture-based inactivated (ccIIV) influenza vaccines could improve seasonal influenza prevention; however, evidence is limited in how protection may differ among non-egg-based vaccines. Methods: We conducted a randomized trial of RIV versus ccIIV to compare vaccine immunogenicity in adults aged 18 to 64 years during the 2024-25 influenza season (ClinicalTrials.gov, NCT06518577). Active surveillance for influenza-like illness was conducted for six months post-vaccination and cumulative incidence of influenza by vaccine type was compared to estimate relative vaccine efficacy. Participants were tested for influenza by reverse-transcription polymerase chain reaction or rapid antigen tests. Immunogenicity was evaluated by hemagglutination inhibition (HAI), virus microneutralization (MN), and neuraminidase inhibition (NAI) assays in a subset of blood specimens collected pre-vaccination and one-month post-vaccination. Results: Among the 591 participants, 25 cases of influenza A were detected; 2.4% cumulative incidence among RIV recipients versus 6.1% among ccIIV recipients. The probability of influenza was 61% lower with RIV than ccIIV (95% confidence interval: 7 to 84). Among 151 participants, post-vaccination HAI and MN titers vaccine components were higher among RIV recipients while NAI titers were higher among ccIIV recipients. Conclusions: RIV provided better protection than ccIIV against influenza A illness in adults during the U.S. 2024-2025 season.

The longitudinal effects of initial influenza exposure on the magnitude, persistence, and antigen specificity of antibody responses during infancy remain incompletely understood. We investigated humoral antibody responses following primary influenza infection or seasonal vaccination in a prospective US birth cohort with weekly respiratory surveillance for influenza infection. Influenza-specific serum IgG binding to H1 and H3 haemagglutinin (HA) antigens, HA inhibition (HAI), and live-virus neutralizing antibody responses were assessed longitudinally. To minimize influence of maternally derived antibodies, analyses of primary exposure responses were restricted to infants for whom influenza-specific maternal antibodies had declined below the assay detection limit before exposure. Antibody responses were compared following primary infection and vaccination and examined after subsequent annual vaccination. We found that maternal influenza-specific IgG declined rapidly during early infancy. Among infants without detectable pre-exposure influenza-specific antibodies, primary influenza infection was associated with greater post-exposure antibody responses and less measurable decline over follow-up than primary vaccination. These groups differed in age, calendar season, and exposure characteristics, limiting direct attribution of these differences to route of exposure. In infants with previous influenza infection followed by vaccination, responses after subsequent vaccination initially showed greater binding to the previously infecting subtype among the tested HA antigens. With repeated vaccination, responses became more distributed across the tested antigens. Our findings reveal differences in the magnitude, persistence, and antigen specificity of antibody responses according to the nature and sequence of influenza exposure. By prospectively capturing early-life exposures, this study provides longitudinal evidence linking exposure history to subsequent humoral antibody responses.

BackgroundCOVID-19 pandemic modified trends of infant bronchiolitis, leading cause of emergency room (ER) attendance in infants in high income countries, primarily due to Respiratory Syncytial Virus. Understanding recent pandemic-related epidemiological shifts could inform affordable prevention efforts to improve sustainability and coverage of prophylactic treatments beyond maternal vaccines and infant monoclonal antibodies. MethodsWe estimated incidence rates (IR) of bronchiolitis ER presentations in 0-6month olds in 2012-2023 in a region-wide cohort of almost 1 million births using administrative health data from Lombardy, Italy. To assess potential contributors, we investigated direct and indirect COVID-19-related factors, including disease severity, shape of the epidemic peak, parental health seeking behaviour and vaccine coverage. We estimated COVID-19 maternal vaccination associations using mothers-infants data linkages and multivariable-adjusted logistic regression. FindingsCompared to pre-pandemic levels, IRs doubled in 2021-2023 (from 2 to [≥] 4/100 person-time). The surge could not be explained by changes in infant age at ER visit, clinical severity or in the shape of the epidemic peak. Adjusted models showed little support for a role of infant routine or maternal COVID-19 vaccination on bronchiolitis episodes (respectively hazard ratio 1.09, 95%CI: 0.98-1.22 and odds ratio 0.91, 95%CI: 0.76-1.09). InterpretationThe post-pandemic increase in infant bronchiolitis is likely driven by multiple epidemiological changes rather than a single factor. As maternal RSV vaccination and infant RSV monoclonal antibodies are introduced and scale up, identifying these mechanisms will be critical to maximise their public health impact, inform complementary prevention strategies, and improve preparedness for future RSV epidemics.

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.

Background: Health Information Exchanges (HIEs) offer a potential resource for timely, population-level infectious disease surveillance by integrating electronic health record data across healthcare systems. Methods: We developed an end-to-end informatics pipeline for near-real-time community-level health surveillance based in a regional HIE serving Southeast Texas. We identified deidentified individual-level COVID-19, influenza, and RSV cases using diagnosis codes and laboratory results and assessed demographic and temporal trends from January 2022 through August 2026. Results: We identified 492,242 COVID-19 cases, 343,977 influenza cases, and 33,159 RSV cases during the study period. Surveillance data captured expected seasonal patterns, including recurring winter COVID-19 and influenza peaks and shifting RSV epidemiology, while enabling monitoring of laboratory test positivity metrics and hospitalization trends across age groups. Conclusions: HIE-based surveillance provides scalable, near-real-time monitoring of disease targets across large populations. HIE infrastructure can enhance public health situational awareness and complement traditional surveillance systems by harmonizing vital health data across systems and providers and delivering timely, standardized, and representative population health indicators.

Background: The 2025/26 influenza season included A(H3N2) subclade K predominance with A(H1N1)pdm09 co-circulation and subsequent prolonged influenza B activity. The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) in the context of genetic and antigenic relatedness to circulating viruses. Methods: We estimated VE by test-negative design among outpatients with medically-attended acute respiratory illness between November and April. We characterized case viruses by whole genome sequencing and hemagglutination inhibition assay. Results: Among 2809/9047 (31%) influenza-positive specimens, 82% (2306/2809) were influenza A with 18% (504/2809) influenza B. Of subtyped influenza A, 85% (1848/2169) were A(H3N2). We sequenced 59% (1099/1848) of A(H3N2) viruses, with 87% (956/1099) subclade K, antigenically-mismatched to subclade J.2 vaccine. VE against A(H3N2) and subclade K was 38% (95% confidence interval: 27%-47%) and 33% (19%-45%). We sequenced 69% (222/323) of A(H1N1)pdm09 viruses, virtually all (n=218) clade 5a.2a.1, including subclades D.3.1 (21%; n=47) and D.3.1.1 (77%; n=171), antigenically-matched to subclade D vaccine. VE against A(H1N1)pdm09, subclades D.3.1 and D.3.1.1 was 28% (4%-47%), -21% (-144%-40%) and 44% (14%-64%). We sequenced 82% (413/504) of influenza B viruses, all B/Victoria, including antigenically-mismatched subclade C.3 (18%; n=74) with D197N gain-of-glycosylation, and antigenically-matched subclade C.5 (82%; n=339) relative to subclade C vaccine. VE against influenza B, subclades C.3 and C.5 was 55% (41%-66%), 10% (-60%-49%) and 68% (51%-79%). Conclusions: The 2025/26 influenza vaccine reduced the risk of A(H3N2), A(H1N1)pdm09 and B/Victoria by over one-third, one-quarter and one-half, respectively. Laboratory-based indicators of vaccine match remain uncertain proxies for actual vaccine protection, reinforcing importance of annual epidemiological monitoring of VE.

Low pathogenic avian influenza A(H7N7) virus detected in a poultry worker in Taiwan, 2026 was related to viruses circulating in Asian wild birds and possessed PB2 E627K, a mammalian adaptation marker. Enhanced surveillance for H7 viruses in poultry and rapid characterization of human cases are essential to assess pandemic potential.

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: Non-medically attended (NMA) and outpatient medically attended (MA) influenza illnesses contribute substantially to influenza disease burden in the United States. We leveraged a household study to estimate out-of-pocket and lost productivity costs of NMA and MA influenza illness. Methods: The Respiratory Virus Transmission Network for Influenza was a 2024-2025 case-ascertained household study at 3 U.S. sites. Influenza-positive index patients and household contacts self-reported daily symptoms, over-the-counter (OTC) medication use, medical care-seeking, time missed from work or activities, and self-collected nasal swabs for PCR testing. We included participants with PCR-confirmed influenza infection and influenza-like-illness symptoms who ever (MA) or never (NMA) sought medical care during follow-up. We obtained costs of OTC medications from retail websites and productivity costs from published values. We calculated OTC medication and lost productivity costs in 2025 USD for MA and NMA influenza separately and household-level lost productivity costs among caregivers for MA and NMA household members. Results: Median out-of-pocket OTC medication costs were $6.38 (interquartile range [IQR] $2.92-$11.60) among 594 MA and $3.72 (IQR $1.50-$7.05) among 153 NMA influenza illnesses. Among participants [≥]15 years of age, median lost productivity was $315 ($149-$743) for MA and $248 ($0-$624) for NMA illnesses. Median household-level lost productivity for caregiving was $148 (households with 1 ill child), $379 (multiple ill children), and $0 ([≥]1 ill adult). Conclusions: Influenza causes substantial lost productivity costs within households. These estimates can inform future economic burden and cost effectiveness analyses.

Background Influenza vaccines have seen many changes over recent years in terms of both policy recommendations and product types. Immune responses and vaccine effectiveness vary by vaccine strain composition and product type. This study aimed to explore this variation on a regional level through examining spatial and temporal autocorrelations of vaccine uptake of different product types within Michigan from 2017 to 2021. Methods Influenza vaccine administration data from the 2017/18 to 2021/22 seasons were obtained from the Michigan Care Improvement Registry. Population size estimates for 2017 and 2019 were obtained from the Michigan Department of Health and Human Services. Age-standardized and age-stratified vaccination rates were computed. Disparate county-level vaccine uptake clusters were constructed using spatial autocorrelation indicators and spatiotemporal clusters were identified using scan statistics. Linear mixed effect models were used to study the impact of social vulnerability and urbanicity level on seasonal influenza vaccination rate. Results Vaccination incidence rates for adjuvanted, recombinant, and nasal sprays vaccines and for any vaccines increased significantly through the study period. County-level spatiotemporal clusters of type-specific uptake rates were identified. Most notably, we identified an emerging cluster with high uptake of adjuvanted vaccine radiating from Ottawa County, located in suburban Grand Rapids, and the disappearance of high uptake cluster for high-dose vaccine uptake in the area. Vaccination rates by any product type were found to vary seasonally and showed weak negative association with more rural regions. The overall vaccination rates appear to be lower among counties with higher social vulnerability in certain urbanicity levels, but social vulnerability and urbanicity were not significantly associated with overall vaccination rate during the study period. Conclusions Vaccine type-specific uptake was spatially and temporally diverse in Michigan between 2017 and 2022. Mid and Northern Michigan had consistently relatively lower vaccination rate compared to other regions in Michigan.

The continued circulation of H5 clade 2.3.4.4b highly pathogenic avian influenza virus (HPAIV) has caused extensive mortality in wild bird populations worldwide with increasing spillover to mammals. In 2022, H5 HPAIV emerged in Svalbard, Norway, with subsequent detections in wild birds, walruses, polar bears, and arctic foxes. To understand the population-level exposure among Svalbard arctic foxes, we analysed body fluids from carcasses trapped in 2006-2015 (n = 56), 2023-2024 (n = 112), and 2024-2025 (n = 94) for antibodies to H5 avian influenza (anti-H5), influenza A nucleoprotein (anti-NP), and neuraminidase subtypes using ELISAs, haemagglutination inhibition (HI), and a multiplex assay. Only three samples from 2006-2015 tested positive for anti-H5 and were interpreted as false positives. In 2023-2024, seropositivity for anti-H5 was high (95%), supported by a lower anti-NP seropositivity (85%) and antibody profiles consistent with mixed H5N1 (42%) and H5N5 (52%) exposure. In 2024-2025, anti-H5 and anti-NP seroprevalences remained high (83% and 57%), with H5N5 (87%) exposure predominating over H5N1 (3%). A subset of anti-H5-positive samples tested positive by HI (2023-2024: 30%; 2024-2025: 14%). Juveniles with exposure limited to the previous season had higher odds of anti-H5 seropositivity in 2023-2024 than in 2024-2025 (OR 5.5). Analysis of paired lung extracts from a subset of individuals (n = 63) yielded results concordant with body fluids, using an indirect anti-H5 ELISA adapted for carnivores. Our findings demonstrate widespread H5 virus exposure. Together with occasional reports of progression to fatal HPAI, this highlights the need for continued population monitoring to evaluate ecological consequences.

Background and Objectives: Influenza vaccination has a strong safety record and is effective in reducing pediatric influenza-associated morbidity and mortality. However, pediatric vaccination coverage (VC) has declined since the 2019/20 influenza season in the United States. We estimated the impact of increased vaccine protection (through increased VC and/or vaccine effectiveness [VE]) on pediatric influenza-associated burden during the 2022/23-2024/25 seasons. Methods: We used a compartmental model and laboratory-confirmed influenza-associated hospitalization, VC, and VE data among children 6 months-17 years to estimate influenza burden from 2022/23-2024/25 (the 'baseline' scenario) and the impact of vaccination. We simulated scenarios that (1) increased VC by five percentage points; (2) increased VE by five percentage points; (3) increased VC and VE by five percentage points; and (4) increased VC to levels achieved in 2019/20 (the season with the highest pediatric VC to date). We estimated the difference in hospitalizations and deaths between each scenario and the baseline scenario. Results: Among children 6 months-17 years, an estimated 120,000 influenza-associated hospitalizations and 1,650 deaths occurred across all seasons at baseline. Increasing VC to 2019/20 levels had the greatest estimated impact, reducing hospitalizations by 8,670 (7.2%) and deaths by 130 (7.9%). Increasing both VC and VE by five percentage points reduced hospitalizations by 6.6% and deaths by 6.7%, whereas increasing VC or VE by five percentage points reduced hospitalizations by 3.1% and deaths by 3.2%. Conclusions: Increasing pediatric influenza vaccination coverage back to 2019/20 levels was estimated to significantly reduce pediatric influenza-associated morbidity and mortality.

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