Influenza and Other Respiratory Viruses

BackgroundDetermining whether SARS-CoV-2 is or will be seasonal like other respiratory viruses is critical for public health planning, including informing vaccine policy regarding the optimal timing for deploying booster doses. To help answer this urgent public health question, we evaluated whether COVID-19 case rates in the United States and Europe followed a seasonal pattern using time series models. MethodsWe analyzed COVID-19 data from Our World in Data from Mar 2020 through Apr 2022 for the United States (and Census Region) and five European countries (Italy, France, Germany, Spain, and the United Kingdom). For each, anomalies were identified using Twitters decomposition method and Generalized Extreme Studentized Deviate tests. We performed sensitivity analyses to determine the impact of data source (i.e., using US Centers for Disease Control and Prevention [CDC] data instead of OWID) and whether findings were similar after adjusting for multiple covariates. Finally, we determined whether our time series models accurately predicted seasonal influenza trends using US CDC FluView data. ResultsAnomaly plots detected COVID-19 rates that were higher than expected between November and March each year in the United States and Europe. In the US Southern Census Region, in addition to seasonal peaks in the fall/winter, a second peak in Aug/Sep 2021 was identified as anomalous. Results were robust to sensitivity analyses. ConclusionsOur results support employing annual protective measures against SARS-CoV-2 such as administration of seasonal booster vaccines or other non-pharmaceutical interventions in a similar timeframe as those already in place for influenza prevention. Summary of the Main PointAlthough SARS-CoV-2 continues to cause morbidity and mortality year-round due to its high transmissibility and rapid viral evolution, our results suggest that COVID-19 activity in the United States and Europe peaks during the traditional winter viral respiratory season.

BackgroundContinued serosurvey for SARS-CoV-2 population immunity is critical for vaccine strain selection and identification of susceptible groups such as young children. We aim to evaluate the use of a high-throughput, low-volume assay to describe strain-specific IgG measurement in a longitudinally followed community-based cohort. MethodsThe longitudinal Household Influenza Vaccine Evaluation study has observed around 300 households annually for acute respiratory illness. SARS-CoV-2 variant-specific IgG (including original, delta, beta, and omicron variants) concentrations were measured using multiplex electrochemiluminescence (ECL), pseudoviral neutralization (PN), and ACE2 inhibition assays in participants who had serum samples drawn between July 1 and December 31, 2021. Spearmans rank correlation coefficient assessed correlation within and between ECL, ACE2, and PN assays. Receiver operating characteristic (ROC) analysis evaluated the performance of ECL and ACE2 assays. Generalized Additive Mixed Models estimated population immunity by age against SARS-CoV-2 variants. ResultsA total of 156 serum samples from 117 participants were selected for this study. Most were from adults and a majority received vaccination during the analysis period. High correlations were observed within ECL (0.99-1.0), ACE2 (0.87-0.99), and between panels: ECL vs. PN (0.95-1.00), ACE2 vs. PN (0.85-0.96). ROC analysis showed medium to high areas under the curve, sensitivity, and specificity for ECL (0.85-0.87; 0.89-0.90; 0.87-0.88) and ACE2 (0.85-0.96; 0.94-1.0; 0.42-0.92). SARS-CoV-2 IgG concentrations are higher in older individuals, plateauing at age 20. ConclusionWe found a high correlation between ECL, ACE2, and PN across variants. Age-specific IgG quantities reflected behavior and infection histories collected by active surveillance.

BackgroundThe comparative risk of post-acute sequelae (PAS) associated with SARS-CoV-2 and influenza virus infection remains unclear. MethodsWe undertook a retrospective cohort study within the Kaiser Permanente Southern California healthcare system of COVID-19 and influenza cases who received acute respiratory illness (ARI) diagnoses in virtual, outpatient, or inpatient settings between 1 September, 2022 and 31 December, 2023. We monitored PAS-associated healthcare utilization across all settings through 180 days after index ARI diagnoses. We estimated adjusted hazard ratios (aHRs) comparing COVID-19 cases to influenza cases, weighting to account for cases probability of retention in follow-up and infection with SARS-CoV-2 or influenza virus at the index ARI episode. ResultsAnalyses included 74,738 COVID-19 cases and 18,790 influenza cases, among whom 35,835 (38.3%), 26,579 (28.4%), 23,388 (25.0%), and 7,726 (8.3%) received care for their index ARI episodes in virtual, ambulatory, emergency department, and inpatient settings, respectively. Risk of PAS diagnoses in any clinical setting was similar among COVID-19 and influenza cases (aHR=1.04 [95% confidence interval: 0.99-1.09] and aHR=1.01 [0.97-1.06] 31-90 and 91-180 days after index, respectively). However, COVID-19 cases experienced higher risk of severe PAS conditions necessitating inpatient care (aHR=1.31 [1.07-1.59] and aHR=1.24 [1.03-1.49] 31-90 and 91-180 days after index, respectively). This heightened risk of severe PAS following COVID-19 was concentrated among patients who required inpatient admission at their index episode. ConclusionsPAS outcomes occur with similar frequency among non-severe COVID-19 cases and influenza cases. However, PAS among COVID-19 cases are more likely to require hospital admission than PAS among influenza cases. Key pointsO_LINon-severe acute respiratory illnesses involving SARS-CoV-2 and influenza virus are associated with similar risk of post-acute sequelae (PAS). C_LIO_LISevere COVID-19 cases experience greater risk of PAS than severe influenza cases. C_LIO_LIPAS following COVID-19 are more likely to necessitate hospital admission. C_LI

Seasonal influenza causes substantial morbidity and mortality in the United States. The U.S. Centers for Disease Control and Prevention (CDC) uses a compartmental framework to estimate the annual disease burden and burden prevented by vaccination for all influenza types and subtypes combined. However, these estimates do not capture underlying shifts in disease burden caused by different circulating influenza virus types or subtypes. We demonstrate an extension of the current framework to estimate disease burden and burden prevented by vaccination for influenza A virus subtypes A(H1N1) and A(H3N2), and influenza type B viruses. We applied this method to data from the 2016/17 to 2019/20 seasons that include age- and virus-specific hospitalizations and vaccine effectiveness estimates, and age-specific vaccination coverage estimates. We estimated the number of symptomatic illnesses, medically-attended illnesses, hospitalizations, and deaths caused by each virus, and the corresponding number prevented by vaccination. Disease burden and vaccine-prevented burden varied substantially by season, age, and virus type or subtype. The greatest disease burden was estimated in 2017/18, whereas 2019/20 had the greatest burden prevented by vaccination. Influenza A viruses contributed most to disease burden in all seasons. Vaccination against influenza B viruses prevented the largest percentage of hospitalizations among children and adults <65 years, whereas vaccination against A(H1N1) prevented the largest percentage of hospitalizations among adults [&ge;]65 years. Overall, our results highlight complex variability in influenza disease burden by season, age, and virus type and subtype. These findings can be used to improve understanding of the factors impacting influenza disease burden each season and to enhance communications of the value of influenza vaccination. HighlightsO_LIEstimates of disease burden and vaccine-prevented burden inform influenza guidance. C_LIO_LIContributions to burden from each virus type and subtype vary by season and age. C_LIO_LIA(H3N2) caused the greatest total disease burden from the 2016/17 to 2019/20 seasons. C_LIO_LIChildren <18 years experienced greater influenza B burden compared with other ages. C_LIO_LIVaccination against A(H1N1) and B prevented the greatest percentage of severe disease. C_LI

BackgroundQuantifying the burden of respiratory syncytial virus (RSV) in adults is challenging compared to influenza, and data among older adults remain scarce in Japan. Country-specific evidence is essential to support RSV vaccination policy. MethodsThis prospective, multicenter study (APSG-J2) targeted hospitalized adults with community-acquired pneumonia (CAP) and other acute respiratory infection (ARI) in seven community-hospitals across four catchment areas in Japan between September 2022 and August 2024. Respiratory samples were analyzed using a multiplex polymerase chain reaction (PCR) kit to detect RSV and influenza. Incidence rates of RSV- and influenza-associated hospitalizations were estimated using study data and national statistics, stratified by age and region. ResultsAmong 3,047 hospitalized patients with CAP/ARI, 1,502 (49.3%) underwent multiplex PCR testing. RSV and influenza were detected in 2.8% and 3.3% of tested patients, respectively. The incidences of RSV-associated CAP/ARI hospitalizations among adults aged [&ge;]65 years were 29 and 36 per 100,000 person-years in the first and second years, respectively, with higher incidences among those aged [&ge;]85 years (150 and 131 per 100,000 person-years). Influenza incidence increased markedly in the second year (from 11 to 71 per 100,000 person-years for adults age [&ge;]65 years), possibly reflecting post-COVID-19 transmission changes. ConclusionsThis is the first active surveillance study in Japan to estimate RSV- and influenza-associated hospitalization incidence among adults during and after the COVID-19 era. The results may still be influenced by the lingering effects of COVID-19 restrictions on social interaction. Continued surveillance is essential to accurately assess RSV burden in the adult population.

BackgroundReduced influenza transmission during the COVID-19 pandemic prompted concern about waning of population immunity that could lead to subsequent surges in circulation. We evaluated this by comparing longitudinal influenza antibody titers in Michigan and Hong Kong, two regions with reduced influenza transmission during the COVID-19 pandemic. MethodsIn two prospective cohort studies (HIVE, Michigan; EPI-HK, Hong Kong), we analyzed longitudinal serum samples collected from 2020 through 2023 from participants without documented influenza virus infection or vaccination. Sera were tested using hemagglutination inhibition assays (HAI) against relevant vaccine strains. Geometric mean titers (GMTs) and fold changes were estimated by region and time. Linear mixed-effects models were used to assess temporal trends. ResultsWe analyzed 173 sera from 57 HIVE participants and 259 sera from 60 EPI-HK participants. Initial GMTs in 2020-21 ranged from 12.3-123.4 in HIVE and 6.3-40.9 in EPI-HK (B/Yamagata-H1N1). Fold changes in GMTs ranged from 1.2-2.6 in HIVE and 0.7-1.0 in EPI-HK. In HIVE models, no significant change in HAI titers over time was detected. In EPI-HK, small but statistically significant monthly declines were observed for select H1N1 (A/Michigan) and H3N2 (A/Hong Kong) strains (e.g., A/Hong Kong: -0.98%, 95% CI: -1.82% to -0.11%). ConclusionMinimal HAI titer waning was observed in both regions. In some cases, antibody levels increased in Michigan, possibly indicating cryptic circulation of strains prior to the 2022/23 influenza season. These findings do not support an "immunity debt" during pandemic restrictions and could help explain the lack of a substantial surge in influenza impact after the COVID-19 pandemic.

BackgroundSeasonal human influenza viruses can escape from antibody-mediated neutralization when amino acid changes occur in the hemagglutinin protein. Routine surveillance identified circulation of an A(H3N2) virus variant in the Netherlands with amino acid substitutions at hemagglutinin positions 158 and 189. These amino acid positions were previously responsible for antigenic change of influenza A(H3N2) viruses and potentially lead to escape of this variant from vaccine-mediated immunity. AimTo characterize the emergence and antigenic properties of N158K and K189R double substitution virus variants. MethodsWe analyzed the geographical and temporal dynamics of the double-substitution variant using a phylogeographic approach and used hemagglutination inhibition assays and antigenic cartography methods to map its antigenic properties. ResultsA(H3N2) viruses carrying K189R were first detected in Guatemala in June 2024, before subsequently gaining the N158K substitution, which was intially detected in Colombia in November 2024, followed by detection in the Netherlands in December 2024. However, detections within Europe remained almost entirely confined to the Netherlands. The proportion of viruses carrying the N158K and K189R substitutions increased to 16% - 24% per collection week of sequenced Dutch viruses during the peak of the epidemic of the 2024-2025 respiratory season. Antigenic characterization of viruses with N158K and K189R substitutions indicated that these are antigenically distinct from the A(H3N2) components of 2025-2026 Northern Hemisphere vaccines, showing 8-192-fold reduction in hemagglutination inhibition titers with antisera against the vaccine strain compared to antisera against the homologous virus. ConclusionsInfluenza A(H3N2) viruses with N158K and K189R escaped recognition by antibodies raised against the 2024-2025 and 2025/2026 Northern Hemipshere vaccine strains in hemagglutination inhibition assays. These variants circulated widely in the Netherlands during the 2024-2025 influenza season, raising concerns about reduced vaccine-mediated protection if such variants would spread more broadly during 2025-2026 Northern Hemipshere season.

BACKGROUNDInfluenza B virus is a significant contributor to annual total and severe cases of influenza, particularly in the young and elderly. Coupling whole virus genome sequencing with the monitoring of influenza cases allows for the identification of increased disease burden and the emergence of novel virus variants. METHODSInfluenza B virus infected individuals were identified in the Johns Hopkins Health Systems network and whole IBV genome sequencing was performed. Phylogenetic analysis and sequence alignments were used to identify the IBV clades and novel virus mutations. The amount of neutralizing antibody activity specific to different IBV clades was measured. RESULTSLate in the 2024-25 Northern Hemisphere influenza season, a surge of IBV cases were identified. The IBV responsible for the surge, C.3re, was a clade C.3 virus that had reassorted with clade C.5.1 viruses and acquired a mutation predicted to mask a key neutralizing antibody epitope on the hemagglutinin protein. The neuramindase gene contained mutations predicted to reduce neutralizing antibody binding and potentially alter oseltamivir sensitivity. The C.3re viruses preferentially infected children but showed no significant increase in disease severity. The C.3re viruses were poorly neutralized by pre and post influenza vaccination serum. CONCLUSIONSThe C.3re IBV genotype that emerged in late in the 2024-25 influenza season is antigenically mismatched with current circulating IBVs and the IBV vaccine strains chosen for the 2025 Southern Hemisphere and 2024-25 Northern Hemisphere season. This may result in lower vaccine efficacy increases in IBV cases in upcoming influenza seasons.

Background & AimsSeasonal respiratory viruses such as influenza cause substantial illness in the United States, over-whelming healthcare facilities and reducing economic productivity. Effective surveillance of these viruses is therefore critical for timely risk communication, strategic resource allocation, and coor-dinated public health responses that mitigate viral spread. Syndromic surveillance, which tracks patient symptoms rather than confirmed diagnostic results, plays an essential role in disease monitoring. While this form of surveillance aids in early trend detection, widespread adoption, particularly for unobserved disease burden estimation, has been hindered by insufficient validation against laboratory-confirmed cases and the lack of accurate syndromic profiles. In this study, we leverage a high-volume medical claims database to develop data-driven syndromic profiles for influenza based on symptom patterns from lab-confirmed cases. We then apply these syndromic profiles to estimate total symptomatic case dynamics and burden (both tested and untested) by geography and demography. Methods & ResultsWe analyzed a large medical claims database covering healthcare visits for over 40% of the United States population annually from 2016 to 2020. We used a regression modeling approach to develop syndromic profiles based on lab-confirmed cases of influenza. With these models, we estimated spatiotemporal dynamics at the county-week scale and season prevalence from time series data on symptom occurrence in healthcare settings. We validated our estimates by comparing them with traditional surveillance data. Symptom-inferred disease estimates aggregated to state and national-levels showed strong agreement with existing surveillance systems in both spatiotemporal trends and magnitude of disease activity. Across all seasons examined, influenza prevalence was spatially heterogeneous, with the southern United States experiencing the highest burden. ImplicationsOptimized syndromic surveillance has promise to serve as a representative, fine-scale, and admin-istratively efficient system for tracking infectious diseases. Public health priorities such as disease forecasting, transmission parameter estimation, and hospital bed allocation can benefit from high-resolution data and disease-specific syndromic profiles. Overall, disease-specific syndromic surveillance will provide more precise monitoring, strengthening public health preparedness and response capabilities.

BackgroundWe assessed associations between antibody concentrations within 7 days of symptom onset and testing positive for influenza virus infection among outpatients enrolled in a test-negative study. MethodsFrom November 2018[boxh]May 2019, study sites in five states obtained serum and respiratory specimens from outpatients aged [&ge;]18 years presenting with acute respiratory illness. Respiratory specimens were tested for influenza virus, and viral clades were identified by genomic sequencing. We measured influenza antibody titers against vaccine and circulating viruses by hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase inhibition (NAI) assays. Percent of patients with HI, MN and NAI titers [&ge;]10 and [&ge;]40 were compared among patients with and without influenza-associated illness, and reduction in odds of confirmed influenza at increasing HI, MN and NAI antibody titers was estimated using logistic regression adjusting for influenza vaccination status and time since beginning of influenza season. ResultsAmong 175 patients with confirmed influenza virus infection, including 112 with influenza A(H1N1)pdm09 and 63 with A(H3N2) (44 clade 3C.3a), and 130 test-negative control patients, higher antibody titers against influenza hemagglutinin or neuraminidase proteins at enrollment were associated with lower odds of influenza virus infection. HI and MN antibody titers against circulating viruses were more strongly associated with protection than titers against vaccine reference viruses. Odds of A(H1N1)pdm09 infection were 44% and 54% lower for each two-fold increase in A(H1N1)pdm09 HI or NAI titer, respectively. Odds of A(H3N2) infection were 46% and 30% lower, respectively, for each two-fold increase in MN or NAI titer against circulating A(H3N2) virus clade. NAI titers were independently associated with lower odds of influenza A(H1N1)pdm09 and A(H3N2) after controlling for HI titer. ConclusionHigher influenza antibody titers against circulating viruses were associated with lower likelihood of influenza virus infection among adult patients with acute respiratory illness. SUMMARYFrom November 2018[boxh]May 2019, we assessed the association between antibody concentrations during acute illness and laboratory-confirmed influenza among adult patients enrolled in a test-negative study in five US states. We found that higher influenza antibody titers were associated with lower likelihood of symptomatic influenza virus infection.

IntroductionFew studies have examined the incidence of virologic-confirmed influenza virus and respiratory syncytial virus (RSV) infections in community-dwelling older adults. MethodsWe enrolled adults aged 60-89 years in Jiangsu Province, China and followed them weekly from December 2015-September 2017 to identify acute respiratory illnesses (ARI), collect illness information and respiratory specimens for laboratory testing. Results1,527 adults were enrolled, 0{middle dot}4% reported ever receiving influenza vaccination. 95 PCR-confirmed influenza ARIs and 22 RSV ARIs were identified, among whom 4-5% required hospitalization. One death associated with RSV ARI while none for influenza ARIs was observed. From December 2015-August 2016, the cumulative incidences of influenza and RSV ARIs were 0{middle dot}8% (95% CI:0{middle dot}3-1{middle dot}4) and 0{middle dot}5% (95% CI:0{middle dot}1-1{middle dot}0), respectively. From September 2016-August 2017, the cumulative incidences were 6{middle dot}1% (95% CI:4{middle dot}7-7{middle dot}7) and 1{middle dot}0% (95% CI:0{middle dot}5-1{middle dot}6); the influenza and RSV ARI-associated hospitalization incidences were 0{middle dot}3% (95% CI:0-0{middle dot}8) and 0{middle dot}1% (95% CI:0-0{middle dot}2). Feverishness was more common in influenza (55%) than RSV ARIs (30%, p=0{middle dot}03). Influenza (12{middle dot}5 days, p=0{middle dot}02) and RSV ARI symptoms (14{middle dot}1 days, p=0{middle dot}15) lasted longer compared to PCR-negative/other ARIs (11{middle dot}0 days). Antibiotic use was more common for influenza (65%, p=0{middle dot}02) and RSV (70%, p=0{middle dot}04) ARIs than other ARIs (51%). ConclusionsWe observed a higher incidence of influenza relative to RSV infections among community-dwelling older adults compared to prior studies. Our findings suggest older adults may benefit from receiving influenza and RSV vaccines to reduce the occurrence of illnesses.

IntroductionWhile seasonal influenza and other respiratory pathogens cause significant morbidity and mortality each year, the community-based burden of these infections remains incompletely understood. Understanding the prevalence, epidemiology, and transmission dynamics of respiratory pathogen infections among community-dwelling individuals is essential during pandemic and epidemic settings and for developing pandemic-preparedness infrastructure. Methods and AnalysisWe present the protocol for a novel, city-wide home-based cross-sectional study in the Seattle Metropolitan area, utilizing rapid delivery systems for self-collection of a nasal swab and return to the laboratory for respiratory pathogen testing. All participation takes place electronically, including recruitment, consent, and data collection. Within 48 hours of participants self-reporting respiratory symptoms, a nasal swab kit is delivered to the household via a courier service. Demographic and illness characteristics are collected at the time of sample collection and recovery and behavioral information collected one week later. Specimens are tested in the laboratory for multiple respiratory pathogens, and results are available on a public website for participants. Ethics and DisseminationThe study was approved by the University of Washington Institutional Review Board (Protocol #00006181). Results will be disseminated through peer-reviewed publications, talks at conferences, and on the Study Website (www.seattleflu.org). Article SummaryO_LIThe findings of this study will inform whether a home-based approach to city-wide respiratory surveillance is possible in epidemic settings C_LIO_LIA key strength of this study is that it is conducted across diverse neighborhoods spanning a major metropolitan area C_LIO_LIClinical findings may not be generalizable, as they are reliant on self-report (vaccination status, symptoms, healthcare utilization, etc.) C_LI

BackgroundHighly pathogenic avian influenza (HPAI) H5 viruses of the A/Goose/Guangdong/1/1996 (GsGd) lineage pose significant global risks to wildlife, domestic animals, and humans. Recent cross-species transmission events to mammals, including humans, highlight this risk. Critical determinants for cross-species and intra-species transmission include the ability to attach to and replicate in respiratory epithelial cells. Although these factors have been studied for HPAI H5N1 viruses in the past, limited studies are available for currently circulating strains. MethodsWe compared level of adaptation to human respiratory tract of a HPAI H5N1 clade 2.3.4.4b (H5N12022) virus with those of well characterized HPAI H5N1 clade 2.1.3.2 (H5N12005) and seasonal H3N22003 viruses by three methods. First, we compared pattern of virus attachment by virus histochemistry. Second, we compared efficiency of infection and replication, as well as innate immune responses in human respiratory epithelium in vitro. Lastly, we compared polymerase complex activity in a minigenome assay. FindingsThe H5N12022 virus attached more abundantly to and replicated more efficiently in cells of the human respiratory tract compared to H5N12005 and H3N2 viruses. This increased replication was not associated with an increased polymerase activity of H5N12022 virus compared to H3N22003 virus. The efficient replication of H5N12022 virus infection induced a robust innate immune response almost comparable to H3N22003. InterpretationThe pattern of virus attachment and replication efficiency of a HPAI H5N12022 virus resembled that of H3N22003 virus more closely than a HPAI H5N12005. This could contribute to an increased risk for both human infection and virus adaptations to humans. FundingThe Netherlands Organization for Health Research and Development Research in contextO_ST_ABSEvidence before this studyC_ST_ABSHighly pathogenic avian influenza (HPAI) H5 viruses of the A/Goose/Guangdong/1/1996 (GsGd) lineage (clade 2.3.4.4b) have the ability to spread to a wide range of domesticated and wild mammalian species, including humans. Cross species transmission and transmission among humans requires-- among other factors--efficient infection of epithelial cells in the respiratory epithelium of the upper respiratory tract. Added value of this studyIn our study we show that a recent clade 2.3.4.4b HPAI H5N1 virus attached to and replicated more efficiently in respiratory epithelium than a clade 2.1.3.2 H5N1 virus that circulated in 2005. Implications of all the available dataThese data suggest that there might be an increased risk of human infections with the currently circulating 2.3.4.4b HPAI H5N1 viruses, which might facilitate opportunities for human adaptation.

Between 2022 and 2025, highly pathogenic avian influenza viruses (HPAIVs) of clade 2.3.4.4b, including four distinct H5 Eurasian (EA) genotypes, were detected in wild birds and mammals in the Svalbard Archipelago and on the island of Jan Mayen. We describe their epidemiology and genomic characteristics to improve understanding of HPAIV occurrence and transmission in the High Arctic. The initial cases in 2022 occurred during summer and involved a glaucous gull (Larus hyperboreus) and great skuas (Stercorarius skua) on Svalbard and Jan Mayen, representing the first detections of HPAIVs in the High Arctic. Three HPAIV genotypes were identified: EA-2020-C (H5N1), EA-2021-AB (H5N1), and EA-2021-I (H5N5). In 2023, HPAIVs were detected in a broader range of bird species, and retrospectively in an Atlantic walrus reported by another research group (Odobenus rosmarus rosmarus). Genotypes identified in 2023 were EA-2020-C (H5N1), EA-2021-I (H5N5), and EA-2022-BB (H5N1). No cases were reported in 2024. In 2025, EA-2021-I (H5N5) was detected in Arctic foxes (Vulpes lagopus) on Svalbard, without preceding detections in wild birds. The foxes exhibited neurological symptoms, and necropsy of one individual revealed the presence of feathers in its stomach. All sequenced viruses from the Arctic foxes uniquely carried the combination of PB2-E627K and PB1-H115Q, which is associated with mammalian adaptation. The detection of multiple genotypes indicates repeated and independent introductions of HPAIVs into these regions. The co-circulation of genetically distinct virus strains in areas of high bird density further suggests that Arctic breeding grounds may facilitate local viral amplification, reassortment, and subsequent dissemination along migratory flyways, including transcontinental spread. Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Influenza A whole genome sequences generated through this study are available under the GISAID accession numbers found in Table 1. All genome sequences and associated metadata supporting the findings of this study can be accessed through the persistent digital object identifier https://doi.org/10.55876/gis8.260211rq. O_TBL View this table: org.highwire.dtl.DTLVardef@15e1921org.highwire.dtl.DTLVardef@c3e91borg.highwire.dtl.DTLVardef@1fcfe78org.highwire.dtl.DTLVardef@a69606org.highwire.dtl.DTLVardef@c36c74_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONDetections of highly pathogenic avian influenza virus (HPAIV) in wild birds and mammals sampled in the Svalbard Archipelago and on Jan Mayen from January 1st, 2022, to August 31st, 2025. C_TABLECAPTION C_TBL

BackgroundInfluenza A(H1N1)pdm09 and A(H3N2) viruses predominated during the 2024-25 U.S. influenza season. We estimated influenza vaccine effectiveness (VE) in the United States against mild-to-moderate outpatient influenza illness by influenza type and subtype in the 2024-25 season. MethodsWe enrolled outpatients aged [&ge;]8 months with acute respiratory illness symptoms including cough in 7 states. Upper respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction (RT-PCR). Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants controlling for age, study site, underlying health status, and month of illness onset. We also estimated VE of current season vaccination among adults stratified by prior season vaccination status. ResultsAmong 6,793 enrolled patients, 2,016 (30%) tested positive for influenza including 961 A(H3N2), 770 A(H1N1)pdm09, and 183 B/Victoria. Overall vaccine effectiveness against any influenza illness was 33% (95% Confidence Interval [CI]: 24 to 41): 27% (95% CI: 14 to 39) against influenza A(H3N2), 37% (95% CI: 24 to 48) against A(H1N1)pdm09, and 40% (95% CI: 12 to 59) against B/Victoria. VE did not differ based on whether or not participants had received influenza vaccine the previous season. ConclusionsInfluenza vaccination during the 2024-25 season protected against circulating influenza viruses, reducing the risk of outpatient medically attended influenza overall by approximately one-third among people who were vaccinated. Key PointsInfluenza vaccine reduced the risk of outpatient acute respiratory illness due to laboratory-confirmed influenza during the 2024-25 season by a third.

BackgroundHigh levels of excess mortality during periods of active influenza circulation in France were observed in the years preceding the COVID-19 pandemic. Some of the factors that affect the rates of influenza associated mortality are influenza vaccination coverage levels in different population groups and practices for testing for influenza and related use of antiviral medications for various illness episodes (including pneumonia hospitalizations) during periods of active influenza circulation in the community. MethodsData on sentinel ILI surveillance and sentinel virological surveillance in France were combined in a framework of a previously developed regression model to estimate the number of deaths associated with the circulation of the major influenza subtypes (A/H3N2, A/H1N1, B/Yamagata and B/Victoria) in France between 2015-2019. ResultsBetween week 3, 2015 and week 2, 2020, there were on average 15403 (95% CI (12591,18229)) annual influenza-associated deaths, of which 60.3% (49.9%,71.9%) were associated with influenza A/H3N2, and 29.5% (13.3%,45.5%) were associated with influenza B/Yamagata. During weeks when levels of ILI consultation in mainland France were above 50 per 100,000 persons, 7.9% (6.5%,9.4%) of all deaths in France were influenza-associated. ConclusionsHigh rates of influenza-associated mortality in France prior to the COVID-19 pandemic suggest that boosting influenza vaccination coverage in different population groups and testing for influenza in respiratory illness episodes (including pneumonia hospitalizations) during periods of active influenza (particularly influenza A/H3N2) circulation in combination with the use of antiviral medications is needed to mitigate the impact of influenza epidemics.

BackgroundA comprehensive description of the combined effect of SARS-CoV-2 and respiratory viruses (RV) other than SARS-CoV-2 (ORV) on hospitalisations is lacking. AimTo compare viral etiology of acute respiratory infections (ARI) hospitalisations before and during two pandemic years from a surveillance network in Quebec, Canada. MethodWe compared detection of ORV and SARS-CoV-2 during 2020-21 and 2021-22 to 8 pre-pandemic influenza seasons in patients hospitalised with ARI who were tested systematically by a multiplex PCR. ResultsDuring pre-pandemic influenza seasons, overall RV detection was 92.7% (1,493) (48.3% respiratory syncytial virus (RSV)) in children and 62.8% (4,339) (40.1% influenza) in adults. Overall RV detection in 2020-21 was 58.6% (29) in children (all ORV) and 43.7% (333) in adults (3.4% ORV, 40.3% SARS-CoV2, both including coinfections). In 2021-22 overall RV detection was 91.0% (201) in children (82.8% ORV, 8.1% SARS-CoV-2, both including coinfections) and 55.5% (527) in adults (14.1% ORV, 41.4% SARS-CoV-2, both including coinfections). Virtually no influenza was detected in 2020-21 and in 2021-22 up to epi-week 2022-9 presented here; no RSV was detected in 2020-21. In 2021-22, detection of RSV was comparable to pre-pandemic years but with an unusually early season. There were significant differences in ORV and SARS-CoV-2 detection between time periods and age groups. ConclusionSignificant continuous shifts in age distribution and viral etiology of ARI hospitalisations occurred during two pandemic years. This reflects evolving RV epidemiology and underscores the need for increased scrutiny of ARI hospitalisation etiology to inform tailored public health recommendations.

Background: Oseltamivir is an antiviral medication for influenza that can reduce the duration of symptoms and may lower the risk of some complications. Recommendations for use of oseltamivir include in the outpatient setting for individuals at higher risk of developing influenza complications. Objectives: To describe oseltamivir initiation and treatment completion among influenza-positive outpatients and identify factors associated with each. Methods: In a U.S. outpatient household transmission study, index participants with laboratory-confirmed influenza provided up to 12 days of detailed information on medication use. We described oseltamivir initiation among index cases and treatment course completion of [&ge;] 10 doses among cases who initiated oseltamivir. We used unadjusted and adjusted logistic regression to identify factors associated with initiation and course completion. Results: Among 823 enrolled index cases, 324 (39%) initiated oseltamivir treatment. Of 406 persons at higher risk for influenza complications, 172 (42%) initiated treatment. Oseltamivir initiation was lowest among children aged 2 to < 5 years (19%) compared to all other age groups. Among 313 cases who initiated oseltamivir, 42% completed the recommended treatment course of [&ge;] 10 doses. Among 163 individuals at higher risk of influenza complications, 69 (42%) completed the recommended treatment course of [&ge;] 10 doses. Children < 2 years were significantly less likely to complete treatment compared to adults aged 18-50 years (aOR: 0.21, 95% CI: 0.04, 0.78, p= 0.030); reasons for discontinuation could not be determined. Conclusions: These findings reveal differences in oseltamivir treatment in an outpatient setting among groups at higher risk for influenza complications.

BackgroundRapid influenza diagnostic tests (RIDT) demonstrate varying sensitivities, often necessitating reverse transcriptase polymerase chain reaction (RT-PCR) to confirm results. The two methods generally require separate specimens. Using the same anterior nasal swab for both RIDT and molecular confirmation would reduce cost and waste and increase patient comfort. ObjectiveThe aim of this study was to determine if RIDT residual nasal swab (rNS) specimens are adequate for RT-PCR and whole genome sequencing (WGS). Study designWe performed RT-PCR and WGS on paired rNS and nasopharyngeal or oropharyngeal (NP/OP) swab specimens that were collected from primary care patients across all ages. We randomly selected 199 and 40 paired specimens for RT-PCR and WGS, respectively, from the 962 paired surveillance specimens collected during the 2014-2015 influenza season. ResultsSensitivity and specificity for rNS specimens were 81.3% and 96.7%, respectively, as compared to NP/OP specimens. The mean cycle threshold (Ct) value for the NP/OP specimen was significantly lower when the paired specimens were both positive than when the NP/OP swab was positive and the nasal swab was negative (25.5 vs 29.5; p<0.001). WGS was successful in 67.5% of the rNS specimens and 55.0% of the NP/OP specimens. ConclusionIt is feasible to use a single anterior nasal swab for RIDT followed by RT-PCR or WGS. This approach may be appropriate in situations where training and supplies are limited. Additional studies are needed to determine if residual nasal swabs from other rapid diagnostic tests produce similar results.

BackgroundSeasonal influenza exhibits distinct spatiotemporal patterns across the United States, yet the geographic clustering of influenza activity remains incompletely understood. This study aims to identify jurisdictions with similar patterns of seasonal influenza epidemics by exploring spatiotemporal dynamics across the United States after the 2009 H1N1 pandemic. MethodsWe analyzed data from U.S. influenza surveillance systems, including outpatient illness surveillance and virologic surveillance. The outpatient illness data included weekly proportions of outpatient visits for influenza-like illness from jurisdictions including all 50 states, while virologic data comprised influenza test positivity results from U.S. public health and clinical laboratories covering all 50 states. We calculated Morans I statistics to assess spatial autocorrelation in peak timing. We also performed k-means clustering on z-normalized time series data and determined optimal clusters using the silhouette method. We then conducted an analysis of variance (ANOVA) to evaluate differences among clusters based on the Morans I statistics and the relative proportions of influenza virus types and subtypes. ResultsOur analysis revealed distinct spatial clusters with significant geographic patterns. We found a consistent grouping of Southeastern states (Georgia, Alabama, Mississippi, Louisiana, and Florida). This clustering pattern was partially explained by earlier seasonal peaks in these jurisdictions and supported by significant spatial autocorrelation in peak timing. While Southeastern states maintained stable cluster associations, Western and Central states showed greater variation in cluster membership across seasons. We also found significant differences between clusters in the Morans I statistics and the proportion of all influenza A virus detections that were influenza A/H1 viruses. However, no significant differences were found in the proportion of all influenza A and B virus detections that were influenza A viruses. ConclusionsThese findings quantify the distinct spatiotemporal patterns of seasonal influenza in the Southeastern United States compared to other regions. Understanding these regional clustering patterns can enhance preparations for upcoming changes in influenza activity and inform targeted public health interventions such as timing of vaccination campaigns. Robust surveillance systems, adaptive approaches, and stable long-term data are essential for effectively addressing regional differences and ultimately strengthening nationwide preparedness for seasonal influenza.