ETIDIOH - NEW

  Abstract The SARS-CoV-2 Omicron subvariant BA.3.2 descends from BA.3 . It emerged two years after BA.3 ceased to circulate and differs by 39 spike mutations from BA.3 . Similar to BA.2.86, which circulated at low levels before giving rise to JN.1, BA.3.2 shows a low but persistent circulation globally . Here, we characterize the phylogenetic origin, infection in cell culture, and neutralization of BA.3.2 using live virus and blood plasma samples collected in South Africa at different stages of the Covid-19 pandemic. Like the Omicron BA.2.86 subvariant, we find that BA.3.2 likely emerged in Southern Africa . We also find that an 871 bp deletion removed ORF7 and ORF8 . In H1299-ACE2 cells, BA.3.2 has lower cytotoxicity measured as plaque area compared to ancestral SARS-CoV-2 but similar to the co-circulating LP.8.1 Omicron subvariant with which it also shares similar replication and infection focus size . BA.3.2 and LP.8.1 exhibit complete escape from neutralization from pre-Omicro...

  Abstract The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health . Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species . Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site , enabling systemic viral spread , alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals . Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation , particularly within the haemagglutinin and polymerase complex . Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccina...

  Summary Background Difficult-to-treat resistant (DTR) Gram-negative infections show resistance to all first-line antibiotics (ie, β-lactams and fluoroquinolones) and have a 40% greater mortality rate than susceptible infections . New antibiotics are now available with improved safety and efficacy and with in-vitro activity against DTR infections; however, their influence on the outcomes of patients with DTR infections remains unclear. We aimed to evaluate whether and why mortality in patients with DTR infections has changed since the introduction of these newer antibiotics in the USA. Methods In this retrospective cohort study in the USA, adult patients (aged ≥18 years) with a DTR Gram-negative infection , defined as microbiological evidence of DTR Enterobacterales, Pseudomonas aeruginosa , or Acinetobacter baumannii and receipt of at least 3 consecutive days of any antibiotic therapy , were identified from hospitals reporting microbiology data in the PINC-AI Healthcare Database....

  Abstract The global expansion of highly pathogenic avian influenza (HPAI) virus A(H5N1) underscores the need for rapid surveillance at high-risk wildlife interfaces. Taiaroa Head (45.7828 S, 170.7333 E) in the South Island of Aotearoa New Zealand hosts a plethora of aquatic wildlife including a large red-billed gull (Chroicocephalus novaehollandiae scopulinus) colony as well as the only mainland breeding colony of northern royal albatross (Diomedea sanfordi). The Royal Albatross Centre is also a major nature tourism destination , attracting tens of thousands of visitors annually, thereby creating a dense ecological and human-wildlife interface vulnerable to viral incursion. We evaluated the GeneXpert II platform using the Xpert Xpress Flu/RSV cartridge as a field-deployable tool for avian influenza virus detection in environmental and wildlife-associated samples . The assay detected synthetic influenza A viral RNA and multiple endemic low pathogenic avian influenza virus subtypes...

  Significance The rising global numbers of SARS-CoV-2 infections highlight the need to assess potential neurodevelopmental and psychiatric impact in children born to infected mothers. Human cohorts have provided conflicting conclusions , while mouse studies have focused on moderate-to-severe infection despite most infections in pregnant women being mild or asymptomatic. Our study shows that mild, respiratory tract–restricted SARS-CoV-2 infection in pregnant mice was sufficient to cause placental inflammation and transient changes in offspring brain gene expression , without altering gross brain structure or behavior under our experimental conditions. These findings suggest that soluble factors induced by maternal respiratory infection mediate placental inflammation and changes in offspring brain gene expression during the fetal and neonatal periods, which resolve in later childhood. Abstract Maternal viral infection during pregnancy has been identified as a risk factor for psychia...

  Abstract Introduction Monoclonal antibodies (mAbs) are critical tools for elucidating viral evolution , informing vaccine design, and developing antiviral therapeutics . Large-animal models, such as the pig , that closely mirror human immune responses are essential for understanding influenza immunity. Methods Pigs were either infected or sequentially immunized with influenza viruses and monoclonal antibodies directed against H3, H5, and H7 influenza virus haemagglutinins were isolated. Antibody specificity, breadth, epitope targeting (head versus stem), neutralizing capacity, and Fc-mediated activity were assessed across influenza subtypes. Results Pigs generated both strain-specific and broadly reactive mAbs targeting haemagglutinin head and stem epitopes . An H3-specific mAb (H3–57) selectively recognized the egg-adapted L194P mutation associated with reduced human vaccine effectiveness . H5 and H7 immunization induced neutralizing antibodies , including cross-group stem mAbs ...

  ABSTRACT Marine mammals, particularly seals, are susceptible to both avian and human influenza A viruses (IAVs), making them potential intermediates for zoonotic virus emergence . In recent decades, repeated transmissions of avian influenza viruses (AIVs) from wild aquatic birds , their natural reservoir, have caused significant mortality in seals . Defining the molecular determinants of viral adaptation in marine mammals , and their implications for replication in human cells , is therefore essential. The non-structural protein 1 (NS1) of AIV, a key antagonist of the interferon (IFN) response , plays a central role in host adaptation . Here, we analyzed NS1 proteins from seal influenza viruses ( H3, H4, H5, H7 , and H10 subtypes) and their closest avian relatives isolated between 1980 and 2023 , and evaluated their function in seal, avian, and human cells . Phylogenetic analysis confirmed multiple bird-to-seal transmission events . Seal-derived NS1 proteins generally contained f...

  Highlights •  A detailed phylogenetic analysis of H5N1 HPAIV isolated from humans was performed. •  All strains infecting humans have acquired substitutions in several key proteins. •  All strains have gained specific substitutions to better adapt to the human host. •  Substitutions in key proteins involved in replication and immune evasion were found. •  A significant degree of polymorphic sites was found in the polymerase complex. •  Substitutions in hemagglutinins and neuraminidases from different clades were found. Abstract Avian Influenza Viruses (AIVs) pose today a very significant risk to global health given the widespread circulation of H5N1 highly pathogenic avian influenza viruses (HPAIV). After decimating the avian population all over the world, these viruses spill over to many different mammal species , causing also fatal outbreaks. As the virus continues to evolve increasing human cases of H5N1 HPAIV have been reported, causing concern t...

  Significance Influenza remains a major global health threat . We introduce oseltamivir-based aziridines that unite transition-state mimicry for tight binding with aziridine-enabled covalent capture of the catalytic tyrosine . This dual function yields potent, mechanism-based neuraminidase inhibition and enables activity-based quantification of active enzyme directly in complex samples. Across N1, N2, and influenza B enzymes , selected compounds show high potency against diverse viral neuraminidases and in live virus replication assays. By combining a clinically grounded scaffold with a reactivity handle, these molecules bridge therapeutic and diagnostic needs and offer a practical platform for neuraminidase imaging and antiviral development. Abstract Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals , including the strains of current concern. Current treatments, such as Zanamivir and Oseltamivir , are limited by noncovalent binding and emergin...

  Abstract Introduction   Increasing occurrence of epidemics and pandemics and concurrent emergence of different pathogens calls for multi-sectoral, multi-pathogen preparedness actions. Data on various factors that drive emergence of diverse pathogens can inform evidence-based preparedness by identifying geographies at-risk. When leveraging evidence within a One Health approach , multiple pathogens can be addressed simultaneously, thereby strengthening countries pandemic preparedness efforts.  Methods   For seventeen priority pathogens ( avian influenza viruses, zoonotic coronaviruses including COVID-19, hemorrhagic fever viruses including Ebola , Henipaviruses , and arboviruses including yellow fever and Zika ), we identified global evidence on animal reservoirs, vectors, environmental suitability , and reported human cases . We discriminated geospatially recorded pathogen detections from a background sample and constructed maps using these datasets to generate an e...

  Abstract Although seasonal influenza vaccination programs are effective at a population level, our data from inactivated influenza vaccine (IIV) cohorts in years 2015-2022 reveal that 50-60% of individuals do not seroconvert following immunization. The underlying mechanisms of vaccine non-responsiveness are far from understood. In this study, we sought to define key determinants of optimal B cell immune responses elicited by seasonal influenza vaccination, and to explore why some individuals fail to elicit humoral immunity following immunization. Immune responses associated with seroconversion and vaccine failure from individuals immunized with IIVs were compared at cellular and molecular levels using single-cell transcriptomics . We analyzed HA-specific B cell immunity across vaccine-responders, breakthrough infections and patients hospitalized with acute influenza. Droplet-based single-cell RNA sequencing and VDJ-sequencing of influenza-specific B cells from stored PBMCs was pe...

  Highlights •  mAbs could enhance our armamentarium against H5N1 in support of pandemic preparedness •  Several mAbs have shown prophylactic and therapeutic efficacy against H5N1 in animal models •  Anti-IAV mAbs that have advanced in clinical trials could be evaluated against H5N1 •  Resistance emergence during mAb treatment was infrequent in pre- and clinical studies Abstract Highly pathogenic avian influenza H5N1 continues to pose a serious zoonotic and pandemic threat due to its increasing cross-species transmission and high virulence in humans . Despite the availability of vaccines and antivirals for seasonal influenza , effective prophylactic and treatment options for H5N1 remain limited . Herein we explore the potential action of monoclonal antibodies (mAbs) against H5N1, focusing on those with demonstrated efficacy in animal models . Most of these mAbs target conserved hemagglutinin epitopes and function as broad neutralizing fusion/entry inhibitors ; n...

  Abstract High pathogenicity avian influenza virus (HPAIV) H5N1 reached the sub-Antarctic and Antarctica in 2023 , subsequently spreading to remote locations within this region where it had devastating impacts on seal, penguin and albatross populations . The threat to marine wildlife over this broad area exemplifies the need to understand H5N1 long-distance dispersal and evolution . We obtained 104 novel viral genomic sequences from samples that we collected at South Georgia, Kerguelen, Crozet, Prince Edward, Falklands/Malvinas Islands and the Antarctic Peninsula in a region spanning 8,000 kilometers . Using recent phylogeographic modeling advances we show that H5N1 spread encompassed numerous transmission events between distant locations, accumulating mammalian-adaptive mutations in the process. Seals are the most affected species, but we reveal that the long-distance eastward virus dispersal better aligns with the long-distance movements of large petrels and albatrosses . The ri...

  Am J Obstet Gynecol REGAN AK, Rowe SL, Birchfield J, Liu J, et al Adherence to Recommended Antiviral Treatment Guidelines for COVID-19 and Influenza during Pregnancy. Am J Obstet Gynecol. 2026 Mar 16:S0002-9378(26)00155. PubMed          BONIFACE ER, Alvergne A, Darney BG, Benhar E, et al Menstrual cycle patterns during acute and long COVID-19 infection among a cohort of individuals with regular menstrual cycles. Am J Obstet Gynecol. 2026 Mar 11:S0002-9378(26)00132. PubMed          BMJ SCANDRETT K, Sitch AJ, Barratt J, Brettell EA, et al Accuracy of glomerular filtration rate estimation based on creatinine and cystatin C for monitoring moderate chronic kidney disease in adults: prospective, longitudinal cohort study. BMJ. 2026;392:e085005. PubMed           Abstract available LANG K How does covid-19 affect the skin? BMJ. 2026;392:s264. PubMed      ...

  Cell VARGAS-MALDONADO N, Shetty N, Ferreri LM, Pauly MD, et al Controlled human influenza infection reveals heterogeneous expulsion of infectious virus into air. Cell. 2026 Mar 19:S0092-8674(26)00232-1. doi: 10.1016/j.cell.2026. PubMed           Abstract available J Immunol VAHED H, Chentoufi AA, Prakash S, Quadiri A, et al CXCL13/CXCR5 chemokine axis promotes antiviral CXCR5+CD19+ B Cells and follicular/effector CXCR5+CD4+ T Cells in the lungs associated with protection from severe and fatal COVID-19 following infection with pathogenic SARS-CoV-2 Delta variant. J Immunol. 2026;215:vkag017. PubMed           Abstract available HANSEN MR, Sedney CJ, Xiao S, Prasad DBR, et al Adult mice with neonatal-like T cell subsets exhibit increased susceptibility to Bordetella pertussis and influenza infection. J Immunol. 2026;215:vkaf361. PubMed           Abstract available ...