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PubMed2026

Recombinant vs Standard Influenza Vaccine in Adults With Severe Obesity: A Randomized Clinical Trial.

BACKGROUND: Individuals with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited. METHODS: The AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m2 were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m2). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for 4 influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed. RESULTS: A total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m2. At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups. CONCLUSIONS: In adults with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.

Humans↗

PubMed2026

Detection and characterization of antiviral-resistant viruses during the influenza season of 2024-25.

UNLABELLED: During the high severity season of 2024-25, CDC with public health partners sequenced and analyzed genomes of >10,000 influenza viruses for antiviral resistance markers. Available sequence-flagged and representative viruses were tested with antivirals using in vitro assays. In the US, three oseltamivir-resistant A(H3N2) viruses had treatment-emergent neuraminidase (NA) mutations, either E119V or R292K. Oseltamivir-resistant A(H1N1)pdm09 viruses with NA-H275Y were detected in 15 states, albeit at a low frequency (0.53%). They belonged to several phylogenetic groups, with hemagglutinin (HA) subclade D.3.1 combined with either NA subclade D.1 or D.2 being most common. Based on shared sequence data, nearly all H275Y viruses from Australia, Canada, and Chile also belonged to these HA and NA subclades. Conversely, most H275Y viruses (68/81) from China belonged to HA subclade C.1.9 and NA subclade D and shared the permissive mutation R257K. Influenza polymerase acidic (PA) mutations conferring 4- to 92-fold decreased baloxavir susceptibility were detected in nine influenza A viruses. Viruses with PA-I38T showed mild attenuation of replicative fitness in three cell lines. Based on available data, NA-H275Y and PA-I38T viruses were collected from patients with no exposure to antivirals. Baseline susceptibility to all US-approved influenza antivirals remained largely unchanged compared to previous seasons. All swine-origin viruses detected in the US had adamantane resistance-conferring marker, M2-S31N, but remained susceptible to other approved antivirals. Monitoring antiviral susceptibility has substantially improved with increased sequencing capacities and bioinformatic support at public health laboratories. Information gained through influenza surveillance has been used to guide recommendations on antiviral use. IMPORTANCE: Circulation of influenza viruses with reduced susceptibility to antivirals can diminish the usefulness of medications prescribed for influenza. This study informs on the prevalence of drug-resistant influenza viruses in the US during the high severity season of 2024-25. It provides information on susceptibility profile to all approved antiviral medications and on replicative fitness of representative drug-resistant viruses. Most drug-resistant viruses were collected from patients who were not exposed to antivirals indicating their ability to transmit from human to human. Whole-genome sequence (WGS)-based analysis is the cornerstone for surveillance, and numerous laboratories have been utilizing this approach. However, CDC laboratory is the only laboratory in the US conducting phenotypic testing of circulating viruses needed to confirm the outcomes of sequence-based analysis and to identify new molecular markers of resistance. Data gathered through virologic surveillance give much-needed information on drug susceptibility of influenza viruses which are used to guide recommendations on antiviral use.

Antiviral Agents↗

PubMed2026

Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026.

In 2023/24, A(H1N1)pdm09 influenza viruses with neuraminidase (NA)-S247N emerged in NA-clade C.5.3.3 carrying NA-I223V, spread internationally, then faded. Such double mutants reappeared sporadically in 2024/25. They expanded again in 2025/26 in NA-clade D.3 viruses carrying NA-S247N after acquiring NA-I223V in Europe - notably Spain, the Netherlands, Finland and France, and beyond. Dutch double mutants from both seasons showed median 12- and 13-fold reduced inhibition by oseltamivir. These findings underscore the need for ongoing genomic and phenotypic monitoring of antiviral susceptibility.

Oseltamivir↗

PubMed2026

Influenza-related Deaths in Young Children: Observations From a German Case Series.

BACKGROUND: Seasonal influenza virus infections remain a major public health burden. During the last years, several case reports of severe influenza infections in children have been published. CASES: We report 4 fatal influenza cases in young children (2-6 years old) which occurred in Southwest Germany in the seasons 2022/23 and 2023/24. All 4 children were previously healthy; a forensic autopsy was conducted due to an unknown cause of death. Postmortem samples from the respiratory tract and organ tissues were tested for respiratory viruses via real-time polymerase chain reaction (RT-PCR) and analyzed by whole-genome sequencing. RESULTS: In 1 child, RT-PCR revealed influenza B virus, and 3 children died with influenza A (H1N1)pdm09 infection. No mutations associated with high virulence were detected. In 1 case, influenza A(H1N1)pdm09 could be cultivated in cell culture from brain tissue. CONCLUSIONS: This case series underlines the potential risk of fatal outcomes of influenza infections in children. This should be considered when re-evaluating the vaccination recommendations for healthy children.

Humans↗

PubMed2026

Deciphering the etiology of the 2024 outbreak of undiagnosed febrile illness in Panzi, Democratic Republic of the Congo.

In late 2024, an outbreak of over 400 cases of undiagnosed febrile illness, predominantly presenting as fever and cough, was reported in Panzi Health Zone, southwestern Democratic Republic of the Congo. Here we conducted an epidemiological and laboratory investigation to determine the etiology of the outbreak. Clinical data and specimens were prospectively collected from 108 individuals, of whom 59/108 (54.6%) were female. Children aged <5 years were the most affected (47/108, 43.5%); 14/32 (43.7%) were malnourished. Oro/nasopharyngeal swabs from 96/108 individuals were PCR tested; 26 blood samples were sequenced. Plasmodium falciparum was detected in 56/108 (51.8%) individuals. Co-infections were also detected, with influenza A(H1N1)pdm09 virus in 16/56 (28.6%) and severe acute respiratory syndrome coronavirus 2 in 10/56 (17.9%) individuals. No novel pathogens were detected via metagenomics. Our findings suggest that the outbreak was primarily associated with a surge in malaria cases, with concurrent viral respiratory infections. Increasing decentralized laboratory capacity and strengthening broader health systems remain crucial for faster outbreak detection and investigation.

Disease Outbreaks↗

PubMed2025

Genome-scale evolution and phylodynamics of swine influenza A viruses in China: a genomic epidemiology study.

BACKGROUND: Pigs are recognised as crucial intermediate hosts for the emergence of influenza viruses of pandemic potential. As the largest pork-producing nation, China hosts a complex ecosystem of swine influenza viruses (SIVs). We aimed to investigate the evolutionary processes, spatiotemporal dynamics, and biological characteristics of SIVs in China. METHODS: From Jan 15, 2016, to Dec 22, 2020, we collected nasal swabs from pigs at eight abattoirs and 16 swine farms in the Guangdong, Henan, and Shandong provinces of China, as part of SIV surveillance. SIVs were detected with RT-PCR. Positive samples underwent viral isolation and genome sequencing. We analysed evolution and spatiotemporal dynamics using the whole genomes of isolated SIVs, as well as genome sequences of SIV isolates from human infections worldwide retrieved from the Global Initiative on Sharing All Influenza Data and GenBank Flu databases up to April 28, 2024. Viral sequences without a sample collection area or date were excluded from the analysis. Viral receptor-binding properties and in-vitro replication of strains isolated in this study were evaluated with a solid-phase binding assay and various cell lines, including Madin-Darby canine kidney cells, porcine alveolar macrophages, primary porcine trachea epithelial cells, human bronchial epithelioid, and human lung adenocarcinoma epithelial (A549) cells. Viral replication and transmission studies were conducted in 33 guinea pigs and 13 pigs. Additionally, we collected serum samples from pig farm workers and members of the general public recruited by the Third Affiliated Hospital of Sun Yat-sen University between Feb 28 and May 11, 2023, to detect specific antibodies against Eurasian avian-like A(H1) and human-like A(H3N2) SIVs using the haemagglutination inhibition assay. FINDINGS: 23 (1·3%) of 1818 nasal swabs collected in abattoirs had SIVs; 22 (0·9%) of 2375 swabs from swine farms had SIVs. Further viral isolation yielded 39 strains of SIV. We identified 534 A(H1N1), 69 A(H1N2), and 92 A(H3N2) SIVs, representing 20 genotypes within the Eurasian avian-like lineage, 14 within the classical swine A(H1) lineage, and 16 within the human-like A(H3N2) lineage. The introduction of the A(H1N1)pdm/09 virus significantly influenced the internal gene pool of SIVs, enhancing genotypic diversity in China. Notably, the Eurasian avian-like A(H1), classical swine A(H1), and human-like A(H3N2) lineages showed human-mediated spread over long distances between provinces, with the Eurasian avian-like A(H1) lineage showing the most prevalent spread pathways. Eurasian avian-like A(H1) SIVs showed a preference for binding to sialic acid α-2,6 glycan receptors, predominantly found in humans, resulting in an increased production of progeny viruses in human airway epithelial cells, as well as effective transmission and infectivity among guinea pigs and pigs. Among 54 eligible serum samples collected from pig farm workers (24 from slaughterhouses and 30 from swine farms), 23 (43%) were seropositive for Eurasian avian-like A(H1) SIVs and 46 (85%) for human-like A(H3N2) SIVs. Among 100 eligible samples from members of the general public, 14 (14%) were seropositive for Eurasian avian-like A(H1) SIVs and 85 (85%) for human-like A(H3N2) SIVs. INTERPRETATION: This study elucidates the evolutionary processes and spatiotemporal patterns of SIVs, highlighting potential risks to public health. These findings are crucial for informing public health interventions that aim to prevent future SIV epidemics in China and other countries worldwide. FUNDING: Scientific Innovation Strategy-Construction of High-Level Academy of Agriculture Science-Distinguished Scholar (R2020PY-JC001).

Animals↗

PubMed2026

Reconstructing the early spatial spread of pandemic respiratory viruses in the United States.

Understanding the geographic spread of emerging respiratory viruses is critical for pandemic preparedness, yet the early spatiotemporal dynamics of the 2009 H1N1 pandemic influenza and severe acute respiratory syndrome coronavirus 2 in the United States remain unclear. While mobility and genomic data have revealed important aspects of pandemic spatial spread, several key questions remain: Did the two pandemics follow similar spatial transmission routes? How rapidly did they spread across the United States? What role did stochastic processes play in early spatial transmission? To address these questions, we integrated high-resolution disease data with a robust, data-efficient inference framework combining air travel, commuting flows, and pathogen superspreading potentials to reconstruct their spatial spread across US metropolitan areas. The two pandemics exhibited distinct transmission pathways across locations; however, both pandemics established local circulation in most metropolitan areas within weeks, driven by several shared transmission hubs. Early spatial spread was more strongly associated with air travel than with commuting, though stochastic dynamics introduced substantial uncertainty in transmission routes, creating challenges for timely detection and control. Simulations indicate that broad wastewater surveillance coverage beyond top transmission hubs coupled with effective infection control may slow initial spatial expansion. Our findings highlight the rapid, stochastic spread of pandemic respiratory pathogens and the difficulties of early outbreak containment.

Humans↗

PubMed2025

Whole-Genome Conservation Analysis for the Specific and Accurate Detection of Influenza A and B Viruses and Respiratory Syncytial Virus by Quadruplex RT-qPCR.

Influenza virus (Flu) and respiratory syncytial virus (RSV) are the primary pathogens responsible for acute respiratory infections. Both viruses are prone to mutations due to the seasonal epidemic, leading to an increasing rate of false-negative results. In this study, comprehensive meta-analyses of the genomes focusing on most conserved fragments have been performed for the four seasonal influenza viruses (two subtypes of Flu A: H1N1 and H3N2; two subtypes of Flu B: Yamagata and Victoria) and the two types of RSV: RSVA and RSVB), respectively. The most conserved sequences of 200 bp were identified as targets of the designed primer/probe sets for RT-qPCR were screened and optimized. Good sensitivities of the optimized primer/probe sets were obtained with the limits of detections of 2.95, 2.82, 1.57, 2.8, 1.19, and 2.12 copies/reaction for H1N1, H3N2, Yamagata, Victoria, RSVA and RSVB, respectively. Eventually, quadruplex qPCR using the four designed primer/probe sets can achieve simultaneous screening of the four viruses at a single tube. Furthermore, the assay's good performance in detecting target viruses from clinical throat swab samples demonstrated its potential for diagnosis of these viruses. The method, based on the identified conserved sequences and primer/probe sets, can effectively reduce false-negative results and rapidly respond to these viruses during respiratory disease outbreaks, or even before their widespread emergence, which aid in preventing outbreaks and guiding clinical treatment.

Humans↗

PubMed2026

Genomic wastewater surveillance of human and animal influenza A viruses in California during the 2024-2025 flu season.

BACKGROUND: Wastewater genomic surveillance provides an opportunity to detect human and animal influenza A virus (IAV). We aimed to implement an IAV genomic surveillance framework agnostic to subtype, which enables recovery of IAV from multiple hosts and estimation of proportions across subtypes. METHODS: We conducted IAV genomic surveillance in wastewater during the 2024-2025 flu season at multiple sites in California and compared these data with available human clinical IAV sequences and test positivity. We applied a custom whole-genome, multi-host IAV probe enrichment panel and adapted our custom expectation-maximization (EM) algorithm to deconvolute IAV mixtures in wastewater and infer subtype relative abundances. Absolute IAV concentrations were quantified using RT-PCR-based assays. H5N1 wastewater and clinical sequences were further characterized by constructing a whole-genome maximum-likelihood phylogenetic tree. Finally, we performed variant analysis to examine amino acid substitutions detected in wastewater. FINDINGS: Our IAV probe enrichment method and EM algorithm successfully enriched all eight segments of three circulating IAV subtypes and accurately estimated subclade relative abundances for mixed IAV samples. Seasonal human H1N1pdm09 and H3N2 were detected throughout the study period from both wastewater and clinical sequencing data, with H1N1 subclades 6B.1A.5a.2a.1 and 6B.1A.5a.2a co-circulating, and H3N2 dominated by subclade 3C.2a1b.2a.2a.3a.1. Wastewater surveillance consistently detected H5N1 clade 2.3.4.4b across three monitored wastewater sites, while clinical H5N1 detections, from anywhere in CA, were sporadic and rare. Whole-genome phylogenetic analysis revealed that wastewater H5N1 sequences clustered with reference sequences associated with dairy cow and avian infections, while all human clinical H5N1 sequences clustered exclusively with reference sequences associated with dairy cow infections. Amino acid substitutions were identified across viral segments, and no mutations associated with mammalian adaptation were observed from wastewater samples. INTERPRETATION: When IAV concentrations were dominated by seasonal human subtypes rather than H5N1, subtype patterns aligned between wastewater and clinical data. While sequencing IAV in wastewater was unable to distinguish if H5N1 detections were due to human or animal infections, it was able to provide clade-level information about H5N1 found in wastewater that could be useful in the future. Wastewater genomic surveillance can complement clinical surveillance, increasing ability to detect all circulating IAV subtypes and enhancing public health preparedness from a One Health perspective.

Journal Article↗