ETIDIOH - NEW

  Abstract Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication . Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes . Model simulations suggested lower antiviral potency against pre-Omicron SARS-CoV-2 variants than against Omicron . We estimated that in vitro assays underestimated in vivo potency by 6- to 7-fold against Omicron variants. Our model suggested that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA was underestimated by approximately 0.4 log10 in the two trials conducted while Omicron variants dominated. Viral area under the curve estimates differed significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in...

  Abstract The H5N1 high pathogenicity avian influenza virus (HPAIV) of clade 2.3.4.4b, which spreads globally via wild birds , has become a major public health concern because it can infect a variety of mammals , including humans . In 2024, infection of dairy cattle with H5N1 HPAIV clade 2.3.4.4b was confirmed in the United States , and subsequent human cases were reported. Although these viruses are highly pathogenic in animal models , human infections have generally been mild , revealing a striking discrepancy . Here, we characterized the cattle-derived human H5N1 isolate A/Texas/37/2024 (TX37-H5N1) using three-dimensional human respiratory organoids derived from induced pluripotent stem (iPS) cells. Despite efficient replication , TX37-H5N1 induced minimal interferon and inflammatory cytokine responses . Bulk and single-cell RNA sequencing revealed reduced STAT1-mediated transcriptional activity in TX37-H5N1-infected organoids compared to the historic H5N1 human isolate A/Vietn...

  Abstract Dipeptidyl peptidase-4 (DPP4) is an established receptor for Middle East respiratory syndrome-related coronaviruses (MERSr-CoVs), while recent studies have identified angiotensin-converting enzyme 2 (ACE2) usage in multiple merbecovirus clades . Yet, receptor usage of many genetically diverse bat MERSr-CoVs remains unclear . Here we show that broadly distributed HKU25 clade merbecoviruses use ACE2 , rather than DPP4, as their receptor. Cryo-electron microscopy revealed that HsItaly2011 and VsCoV-a7 strains engage ACE2 similarly to HKU5 but with remodelled interfaces and distinct orthologue selectivity, suggesting a shared evolutionary origin of ACE2 recognition . EjCoV-3, a close relative of the DPP4-using BtCoV422, showed broad multi-species ACE2 tropism and preadaptation to human ACE2 . Several ACE2 glycans and residues within or near the binding interface were identified as determinants of orthologue selectivity. These viruses remain sensitive to several broadly neutr...

  Clin Infect Dis CALABRESE C, Wang Y, Duggal A, Huang S, et al Effectiveness of Nirmatrelvir/Ritonavir or Molnupiravir Use in Immunocompromised Patients on B-Cell-Depleting Therapy With COVID-19: A Target Trial Emulation Study. Clin Infect Dis. 2025 Oct 24:ciaf521. doi: 10.1093. PubMed           Abstract available FONG Y, Huang Y, Huang Y, Woo W, et al Analysis of antibody markers as immune correlates of risk of severe COVID-19 in the PREVENT-19 efficacy trial of the NVX-CoV2373 recombinant protein vaccine. Clin Infect Dis. 2025 Oct 25:ciaf558. doi: 10.1093. PubMed           Abstract available KABORE JL, Laffont B, Diop M, Tardif MR, et al Real-World Effectiveness of Nirmatrelvir-Ritonavir in Preventing Coronavirus Disease 2019-Associated Hospitalization: A Population-Based Cohort Study in the Province of Quebec, Canada. Clin Infect Dis. 2025 Oct 29:ciaf145. doi: 10.1093. PubMed    ...

  Arch Virol YIN Y, Chen J, Chen S, Huang J, et al The SARS-CoV-2 N protein disrupts G3BP1 function and alters lipid metabolism in COVID-19 pathogenesis. Arch Virol. 2025;170:237. PubMed           Abstract available Biochem Soc Trans CALL MJ, Call ME, Wu X Insights from deep mutational scanning in the context of an emerging pathogen. Biochem Soc Trans. 2025;53:1169-1179. PubMed           Abstract available BMC Pediatr VASQUEZ-LOARTE T, Guerra GA, Saldarriaga EM, Torres-Gomez L, et al Healthcare access satisfaction before and during the COVID-19 pandemic among Peruvian children with down syndrome. BMC Pediatr. 2025;25:874. PubMed           Abstract available Drugs SYED YY Clesrovimab: First Approval. Drugs. 2025;85:1487-1492. PubMed           Abstract available J Exp Med BISSETT C, Yong L, Spencer AJ, Ma FNL, et al Heterologo...

  ABSTRACT Subtype H3N2 influenza A viruses (IAVs), which emerged in 1968 to cause a pandemic, have shown continual circulation and adaptation that has necessitated frequent updates of candidate vaccine viruses . Here, we sought to determine how genetic changes in the hemagglutinin (HA) and neuraminidase of 21 antigenically distinct H3N2 IAVs isolated from 1968 to 2019 correlate with mammalian fitness and adaptation. We found a surge of adaptation between 1997 and 2002 , resulting in the emergence of A/Fujian/411/2002 (H3N2) and poor vaccine efficacy , leading to an epidemic during the 2003–2004 season. This surge was characterized by a large reduction in binding to mammalian-type α2,6-linked sialic acids and increased infectivity and replication kinetics in humanized Madin-Darby canine kidney cells. HA glycosylation also increased most rapidly from 1968 to 2004 and then plateaued. Symptomatic infections were only evident in mice following inoculation with viruses isolated in the 1...

  ABSTRACT Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites . Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission . In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency . We identified tissue-specific virus genotypes , in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. ...

  ABSTRACT An increase in the number of human cases of influenza A/H5N1 infection in the USA has raised concerns about the pandemic potential of the virus. Pre-existing population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody titers were detected in a cohort of 73 individuals . Conversely, bovine A/H5N1 NA-binding and neuraminidase-inhibiting antibody titers were comparable to those against a human A/H1N1 NA at baseline . Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1-n...

  Abstract Recently, highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses have caused mass mortality events in seabirds worldwide, raising concern for long-lived species with low reproductive rates. Using individual-level data from the 2022 mass mortality event in northwestern European Sandwich terns (Thalasseus sandvicensis), we show that older individuals were disproportionately more affected , while no sex bias was observed. This age-specific mortality likely removed the most experienced individuals from the population. Our findings highlight a previously underappreciated mechanism through which HPAI outbreaks may impair the resilience of long-lived avian populations . Competing Interest Statement The authors have declared no competing interest. Funder Information Declared German Federal Agency for Nature Conservation (BfN) Federal Ministry for the Environment, Climate Action, Nature Conservation and Nuclear Safety (BMUKN) Source: BioRxIV,  https://www.b...

  Abstract Background :  Monitoring antigenic drift in human influenza A viruses is essential for vaccine strain selection and ensuring protection against circulating strains. Antigenic drift is traditionally assessed using ferret antisera , which provide monospecific responses , and human vaccinee sera , which reflect exposure to multiple antigens. In this study we evaluated the pig as an alternative source of antisera to study antigenic drift compared to immune responses in ferrets and humans. We included seasonal influenza A(H1N1pdm09) human viruses that had shown different antigenic characteristics when using ferret or human antisera.  Methods :  Pairs of pigs were inoculated with six human A(H1N1)pdm09 viruses circulating between 2019 and 2023, a period of marked antigenic drift. Pig and ferret antisera were analysed by hemagglutination inhibition (HI) and virus neutralization (VN) assays.  Results :  Pigs were successfully infected with all strains, s...

  Key Points -- Question :  Have asymptomatic infections with highly pathogenic avian influenza A(H5N1) virus been reported in humans? -- Findings:  This scoping review of published reports through August 25, 2025, identified 10 reports of 18 cases of asymptomatic infection with A( H5N1 ) virus, including 2 cases with molecular and serologic confirmation and 16 cases with molecular confirmation alone. Symptom ascertainment methods varied among reported cases. -- Meaning:   Asymptomatic human avian influenza A(H5N1) virus infections have been infrequently reported , with most lacking serologic confirmation; prospective surveillance studies with serial respiratory and serum sampling and detailed symptom monitoring for persons with high-risk exposures could provide data to inform future public health responses. Abstract Importance    Since 1997, more than 1000 infections with highly pathogenic avian influenza A(H5N1) virus among humans have been reported globa...

  Abstract Background Changes in the vaccine advisory process in the United States have disrupted immunization guidance , which reinforces the need for independent evidence review to inform decisions regarding immunization for respiratory viruses during the 2025–2026 season. Methods We conducted a systematic review of U.S.-licensed immunizations against coronavirus disease 2019 (Covid-19), respiratory syncytial virus (RSV), and influenza . We searched databases on PubMed/MEDLINE, Embase, and Web of Science for updates of the most recent review by the Advisory Committee on Immunization Practices (ACIP) Evidence-to-Recommendations for each disease, which was performed during the 2023–2024 period. Outcomes included vaccine efficacy and effectiveness against hospitalization, other clinical end points, and safety. Results Of 17,263 identified references, 511 studies met the inclusion criteria. Covid-19 mRNA vaccines against the XBB.1.5 subvariant had pooled vaccine effectiveness against...

  Abstract Highly pathogenic avian influenza virus H5N1 has been infecting dairy herds in the U.S. since its initial incursion into cows in early 2024 . Although national strategies have aimed to detect affected herds , the best way to surveil herds for the H5N1 virus has not been formally studied and we also do not understand herd-level patterns of infection . To understand infection patterns of H5N1 in dairy herds over time, we conducted early surveillance of non-affected farms in California in the Fall of 2024 in an observational study. Daily bulk tank milk (BTM) samples were submitted from each herd and tested for influenza A (IAV) via rRt-PCR. In a subset of herds, IAV testing of multiple excretion types from cattle of different classes and pen-level daily milk was also completed soon after BTM detection. Daily detections of IAV occurred in BTM for a minimum of 33 days , with some herds continuing to have detection beyond a 75-day window. BTM Ct nadirs were seen between 1-3 we...

  Abstract Since 2020, high pathogenicity avian influenza virus (HPAIV) infections in wild birds have been frequently reported . Because HPAIV infection has occasionally caused outbreaks in captive rare birds , application of antiviral drugs for treatment purposes against them has been considered from the perspective of conservation medicine . In this study, the therapeutic efficacy of baloxavir marboxil (BXM) was evaluated using a duck model to help establish the post-infection treatment for rare birds . Sixteen four-week-old ducks were divided into four groups and intranasally inoculated with the HPAIV strain A/crow/Hokkaido/0103B065/2022 ( H5N1 ). BXM was orally administered once daily at doses of 12.5, 2.5, 0.5, and 0 mg/kg to each of the four groups from 2 to 6 days post-infection. Blood samples were collected at 2, 8, and 24 hours after the initial BXM administration to measure the plasma concentrations of its active form, baloxavir acid (BXA). All ducks were monitored until ...

  Abstract Avian influenza viruses (AIVs) are a global public health risk; human infection is typically associated with high mortality . While the relationship between several mammalian adaptive mutations and host factors have been described, it is unknown whether additional uncharacterised mutations lead to adaptation. Here, we combine phylogenetic analysis and complementary experimental methods to quantify the impact of novel mutations that emerge at the avian-mammal interface . We constructed phylogenetic trees of mammalian and avian influenza sequences for the polymerase (PA, PB1, PB2) and nucleoprotein (NP) segments and identified potential avian to mammal spillover events. We found >6500 mutations across the polymerase and NP, including known signatures of mammalian adaptation such as PB2 E627K and D701N which occurred independently in mammals 143 and 56 times respectively. We selected 95 mutations which were mostly undescribed and emerged independently multiple times in a...

  Br J Anaesth THOMAS C, Pearse RM Socioeconomic deprivation and health inequity: independently associated with postoperative outcomes, and does this matter? Br J Anaesth. 2025;135:1141-1143. PubMed           Abstract available Clin Infect Dis TARTOF SY, Aliabadi N, Goodwin G, Slezak J, et al Estimated Vaccine Effectiveness for Respiratory Syncytial Virus-Related Acute Respiratory Illness in Older Adults: Findings From the First Postlicensure Season. Clin Infect Dis. 2025 Oct 21:ciaf496. doi: 10.1093. PubMed           Abstract available MANABE YC, Hamill MM, Palamountain KM, Achenbach CJ, et al The Critical Importance of Clinical Use Case to Inform Point-of-Care Technology Development: A Case Study of Human Immunodeficiency Virus Nucleic Acid Assays in the United States. Clin Infect Dis. 2025 Oct 23:ciaf510. doi: 10.1093. PubMed           Abstract available Graefe...

  Antiviral Res BESSONNE M, Morel J, Nevers Q, Groutsch J, et al Inhibition of influenza virus replication by artificial proteins (alphaReps) targeting its RNA-polymerase. Antiviral Res. 2025 Oct 21:106300. doi: 10.1016/j.antiviral.2025.106300. PubMed           Abstract available BMC Pediatr WONG K, Ducharme R, Murphy MSQ, Clarke AE, et al SARS-CoV-2 infection in pregnancy and infant outcomes in the first year of life: a retrospective cohort study. BMC Pediatr. 2025;25:842. PubMed           Abstract available MAGGIO ABR, Palomo S, Joye R, Huguet H, et al Reduced aerobic capacity in children with multisystem inflammatory syndrome in children (MIS-C) after PICU admission: a retrospective cohort study, 2020-2022. BMC Pediatr. 2025;25:835. PubMed           Abstract available Cell HICKMAN HD, Moutsopoulos NM Don't forget to floss! An innovative approach for vaccine del...