#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

{Northern Ireland} Over 23k 26-week-old grandparent and parent broiler breeders' premises. Positive test for HPAI H5N1. Clinical signs presented prior to testing.

Source: WOAH, https://wahis.woah.org/#/in-review/6872

____

Death of Sardanapalus, Eugene Delacroix (1827)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/eugene-delacroix/death-of-sardanapalus-1827-1

____

H128N Substitution in the Sa #Antigenic Site of HA1 Causes Antigenic Drift Between #Eurasian Avian-like #H1N1 and 2009 #Pandemic H1N1 #Influenza Viruses

 

Abstract

The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy. This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and A/Guangdong-Maonan/SWL1536/2019 (GD1536, 2009/H1N1). Cross-hemagglutination inhibition (HI) assays revealed a significant antigenic disparity, with a 16-fold reduction in heterologous versus homologous HI titers. Comparative sequence analysis identified 22 amino acid differences across the five major antigenic sites (Sa, Sb, Ca1, Ca2, and Cb) of the HA1 subunit. Using reverse genetics, a panel of mutant viruses was generated. This study revealed that a single histidine (H)-to-asparagine (N) substitution at residue 128 (H3 numbering) in the Sa antigenic site acts as a primary determinant of antigenic variation, sufficient to cause a four-fold change in HI titers and a measurable drift in antigenic distance. Structural modeling via AlphaFold3 and PyMOL software suggests that the H128N mutation may alter the local conformation of the antigenic site. It is plausible that H at position 128 could exert electrostatic repulsion with adjacent amino acids, whereas N might facilitate hydrogen bond formation with neighboring residues. These interactions would potentially lead to structural changes in the antigenic site. Our findings confirm that residue 128 is a critical molecular marker for the antigenic differentiation of EA H1N1 and 2009/H1N1 viruses. The study underscores the necessity of monitoring specific HA mutations that could reduce cross-reactivity and provides valuable insights for refining vaccine strain selection and pandemic preparedness strategies.

Source: Viruses, https://www.mdpi.com/1999-4915/17/10/1360

____

#Coronavirus Disease Research #References (by AMEDEO, October 11 '25)

 

Antiviral Res

1. SCHRELL L, Scheibner D, Dickmanns A, Stegmann KM, et al
   Inhibitors of pyrimidine synthesis synergize with N4-hydroxycytidine to diminish influenza virus replication.
   Antiviral Res. 2025 Oct 3:106286. doi: 10.1016/j.antiviral.2025.106286.
   PubMed         Abstract available
   
   

   
   BMJ

2. WISE J
   Covid-19: Excluding doctors from vaccination programme puts patients at risk, clinicians warn.
   BMJ. 2025;391:r2141.
   PubMed        
   
   

   
   Clin Infect Dis

3. ATMAR RL, Abate G, Deming ME, George SL, et al
   Emerging and Pandemic Pathogens: Lessons Learned From a Clinical Research Network.
   Clin Infect Dis. 2025;81.
   PubMed         Abstract available
   
   
4. JANO K, Babu TM, Kottkamp AC, Rebolledo PA, et al
   Historical Advances in Clinical Trial Design and Expanding Representation as the New Frontier for Innovation.
   Clin Infect Dis. 2025;81.
   PubMed         Abstract available
   
   
5. BELSHE RB, Bernstein DI, Edwards KM, Frey SE, et al
   Vaccine and Treatment Evaluation Units: A Historical Perspective.
   Clin Infect Dis. 2025;81.
   PubMed         Abstract available
   
   

   
   Int J Infect Dis

6. WAN EYF, Choi MH, Wang B, Xu Y, et al
   Comparative Effectiveness of Combination Therapy with Nirmatrelvir-Ritonavir and Molnupiravir versus Monotherapy with Molnupiravir or Nirmatrelvir-Ritonavir in Hospitalised COVID-19 Patients: A Target Trial Emulation Study.
   Int J Infect Dis. 2025 Oct 3:108097. doi: 10.1016/j.ijid.2025.108097.
   PubMed         Abstract available
   
   
7. KIM JA, Park S, Cho H, Jeong NY, et al
   Sex Differences in Adverse Event Reporting Rates Following COVID-19 Vaccination in South Korea During the Pandemic.
   Int J Infect Dis. 2025 Oct 6:108107. doi: 10.1016/j.ijid.2025.108107.
   PubMed         Abstract available
   
   
8. FARINAS RP, Alonso-Sardon M, Solis P, Alonso BR, et al
   The impact of the SARS-CoV-2 pandemic on the development of respiratory infections caused by Aspergillus spp., Mucor spp., and Pneumocystis jirovecii within the National Health System of Spain.
   Int J Infect Dis. 2025 Oct 7:108101. doi: 10.1016/j.ijid.2025.108101.
   PubMed         Abstract available
   
   
9. LI Y, Sun C, Zhao T, Ni Y, et al
   Etiology of Initial Treatment Failure in Non-immunosuppressed Adult Patients with Community-acquired Pneumonia.
   Int J Infect Dis. 2025 Oct 8:108110. doi: 10.1016/j.ijid.2025.108110.
   PubMed         Abstract available
   
   
10. SONG JY, Choi WS, Heo JY, Kim YR, et al
    Safety and immunogenicity of a homologous booster dose of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: 12 months follow-up result of an open-label, non-randomised extension of a phase 1/2 trial.
    Int J Infect Dis. 2025 Oct 8:108108. doi: 10.1016/j.ijid.2025.108108.
    PubMed         Abstract available
    
    

    
    J Infect

11. FOULKES S, Munro K, Sparkes D, Khawam J, et al
    Prevalence and impact of SARS-CoV-2, influenza, respiratory syncytial virus (RSV) infection and respiratory illness on UK healthcare workers during winter 2023/24 (September 2023 to March 2024): SIREN cohort study.
    J Infect. 2025;91:106620.
    PubMed         Abstract available
    
    

    
    J Med Virol

12. TIAN Y, Zhou Y, Wang Q, Li X, et al
    Proteomic and Phosphoproteomic Profiling of Kidney in Rhesus Macaques With SARS-CoV-2 Infection.
    J Med Virol. 2025;97:e70633.
    PubMed         Abstract available
    
    
13. PASITTUNGKUL S, Thongpan I, Thongmee T, Thatsanathorn T, et al
    Longitudinal RSV Antibody Trends in Thai Children (0-8 Years): Association With Seasonal Outbreak Patterns and Potential Immunity Debt During the COVID-19 Pandemic.
    J Med Virol. 2025;97:e70629.
    PubMed         Abstract available
    
    

    
    J Virol

14. ZAIB W, Kaviani C, Kang X, Gao Y, et al
    Porcine hemagglutinating encephalomyelitis virus VW572 (not Gent/PS412 and Labadie) uses the CD81 receptor and MVB-derived exosomal pathway for efficient entry and spread in neuronal cells.
    J Virol. 2025 Oct 8:e0117125. doi: 10.1128/jvi.01171.
    PubMed         Abstract available
    
    
15. PERRY JK, Itskanov S, Bilello JP, Lansdon EB, et al
    A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription.
    J Virol. 2025 Oct 8:e0145725. doi: 10.1128/jvi.01457.
    PubMed         Abstract available
    
    
16. MITCHELL JK, Mastrodomenico V, Hartnett J, Heelan WJ, et al
    A HiBiT-tagged pseudovirus-like particle platform for safe, rapid quantification of virus neutralization and antibody-dependent enhancement.
    J Virol. 2025 Oct 8:e0099125. doi: 10.1128/jvi.00991.
    PubMed         Abstract available
    
    
17. WANG W, Du P, Zhao Y, Liang Y, et al
    Biomimetic nanovaccines with self-adjuvant effects induced broad-spectrum neutralizing antibodies against SARS-CoV-2 infection in rodents.
    J Virol. 2025 Oct 10:e0031525. doi: 10.1128/jvi.00315.
    PubMed         Abstract available
    
    

    
    JAMA

18. SHAH J
    Through the Glass.
    JAMA. 2025 Oct 9. doi: 10.1001/jama.2025.18165.
    PubMed        
    
    
19. ANDERER S
    COVID-19 Linked to Lasting and Underrecognized Smell Impairment.
    JAMA. 2025 Oct 10. doi: 10.1001/jama.2025.17491.
    PubMed        
    
    

    
    N Engl J Med

20. CAI M, Xie Y, Al-Aly Z
    Association of 2024-2025 Covid-19 Vaccine with Covid-19 Outcomes in U.S. Veterans.
    N Engl J Med. 2025 Oct 8. doi: 10.1056/NEJMoa2510226.
    PubMed         Abstract available
    
    

    
    Nat Ment Health

21. KESSLER RC, Millikan-Bell AM, Edwards ER, Gildea SM, et al
    Effects of exposure to pandemic-related stressors on anxiety and mood difficulty during versus before the COVID-19 pandemic in United States Army soldiers and veterans.
    Nat Ment Health. 2025 Sep 29:10.1038/s44220-025-00505.
    PubMed         Abstract available
    
    

    
    Zhonghua Jie He He Hu Xi Za Zhi

22. WANG MC, Liu X, Hu K
    [Intermittent hypoxia exposure in the rehabilitation of long COVID patients].
    Zhonghua Jie He He Hu Xi Za Zhi. 2025;48:961-964.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, October 11 '25)

 

Ann Intern Med

1. LE VU M, Matthes KL, Schneider EB, Moerlen A, et al
   Maternal Influenza-Like Illness and Neonatal Health During the 1918 Influenza Pandemic in a Swiss City.
   Ann Intern Med. 2025 Oct 7. doi: 10.7326/ANNALS-24-03796.
   PubMed         Abstract available
   
   

   
   Antiviral Res

2. SCHRELL L, Scheibner D, Dickmanns A, Stegmann KM, et al
   Inhibitors of pyrimidine synthesis synergize with N4-hydroxycytidine to diminish influenza virus replication.
   Antiviral Res. 2025 Oct 3:106286. doi: 10.1016/j.antiviral.2025.106286.
   PubMed         Abstract available
   
   

   
   Epidemiol Infect

3. VAN DER ROEST B, Fischer EAJ, Klinkenberg D, Bootsma MCJ, et al
   Phylodynamic inference suggests introductions as main driver of Mpox Clade II outbreak in 2022 in Slovenia.
   Epidemiol Infect. 2025;153:e115.
   PubMed         Abstract available
   
   
4. WOLDEGIORGIS M, Bloomfield L, Korda R, Cadby G, et al
   Factors associated with persistence or recovery from long COVID 6 months post-SARS-CoV-2 infection.
   Epidemiol Infect. 2025;153:e116.
   PubMed         Abstract available
   
   

   
   J Epidemiol Community Health

5. ROMANO CJ, Nianogo RA, Hoover C, Quint JJ, et al
   Evaluating the effect of the end of the COVID-19 uninsured programme on COVID-19 vaccine administration in California: a quasi-experimental study.
   J Epidemiol Community Health. 2025;79:821-827.
   PubMed         Abstract available
   
   

   
   J Exp Med

6. CHANGROB S, Yasuhara A, Park S, Bangaru S, et al
   Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2.
   J Exp Med. 2025;222:e20251146.
   PubMed         Abstract available
   
   

   
   J Infect

7. FOULKES S, Munro K, Sparkes D, Khawam J, et al
   Prevalence and impact of SARS-CoV-2, influenza, respiratory syncytial virus (RSV) infection and respiratory illness on UK healthcare workers during winter 2023/24 (September 2023 to March 2024): SIREN cohort study.
   J Infect. 2025;91:106620.
   PubMed         Abstract available
   
   

   
   J Virol

8. SHETTY N, Shephard MJ, Rockey NC, Macenczak H, et al
   Correction for Shetty et al., "Influenza virus infection and aerosol shedding kinetics in a controlled human infection model".
   J Virol. 2025 Oct 7:e0135425. doi: 10.1128/jvi.01354.
   PubMed        
   
   

   
   PLoS Comput Biol

9. O'NEILL X, White A, Northrup GR, Saad-Roy CM, et al
   Superspreading and the evolution of virulence.
   PLoS Comput Biol. 2025;21:e1013517.
   PubMed         Abstract available
   
   
10. TEITELBAUM CS, Casazza ML, Overton CT, Matchett EL, et al
    Host responses and viral traits interact to shape the impacts of climate warming on highly pathogenic avian influenza in migratory waterfowl.
    PLoS Comput Biol. 2025;21:e1013451.
    PubMed         Abstract available
    
    
11. PINETTES T, Leclerc QJ, Jean K, Temime L, et al
    The quarantine hospital strategy as a way to reduce both community and nosocomial transmission in the context of a COVID-like epidemic.
    PLoS Comput Biol. 2025;21:e1013548.
    PubMed         Abstract available
    
    
12. STEYN N, Chadeau-Hyam M, Elliott P, Donnelly CA, et al
    A Bayesian model for repeated cross-sectional epidemic prevalence survey data.
    PLoS Comput Biol. 2025;21:e1013515.
    PubMed         Abstract available
    
    
13. DU H, Zahn MV, Loo SL, Alleman TW, et al
    Improving policy design and epidemic response using integrated models of economic choice and disease dynamics with behavioral feedback.
    PLoS Comput Biol. 2025;21:e1013549.
    PubMed         Abstract available
    
    

    
    PLoS Med

14. LEWNARD JA, Malden DE, Hong V, Skela J, et al
    Comparative risk of post-acute sequelae among adults following SARS-CoV-2 or influenza virus infection: A retrospective cohort study among United States adults.
    PLoS Med. 2025;22:e1004777.
    PubMed         Abstract available
    
    

    
    PLoS One

15. LOMELI A, Escoto AA, Reyes B, Kornher K, et al
    Sources of successful participant engagement in a public health research study: A focus on a Latino community.
    PLoS One. 2025;20:e0321910.
    PubMed         Abstract available
    
    
16. TITUS AR, Kanchi R, Adhikari S, Thorpe LE, et al
    Time-varying associations between diabetes and mortality following COVID-19: Evidence from a U.S. Veteran population.
    PLoS One. 2025;20:e0333052.
    PubMed         Abstract available
    
    
17. LIU HH, Battaglia J, Wu TT
    Impact of COVID-19 on English Football Premier League: Analyzing rankings and home advantage using extended Bradley-Terry models.
    PLoS One. 2025;20:e0332627.
    PubMed         Abstract available
    
    
18. MILLER EM, Boyce RM, Kipp AM, Newby LK, et al
    Incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in North Carolina from December 2020 - February 2022.
    PLoS One. 2025;20:e0332645.
    PubMed         Abstract available
    
    
19. REVELJ M, Wessberg A, Carlsson Y, Lindqvist M, et al
    Reclaiming motherhood through shame, distance, and gratitude-A phenomenological study of Swedish women's lived experiences of giving birth while ill with COVID-19.
    PLoS One. 2025;20:e0333937.
    PubMed         Abstract available
    
    
20. LAN WY, Cai SS, Lu Q, Tang F, et al
    Identification of shared key genes in Rheumatoid Arthritis and COVID-19 and their relevance as diagnostic biomarkers and with immune infiltration: New insights from bioinformatics analysis.
    PLoS One. 2025;20:e0333886.
    PubMed         Abstract available
    
    
21. SHOBHA M, Morgan K, Tan MP
    Exploring the social and emotional impact of COVID-19 on older residents of the Greater Klang Valley, Malaysia: A qualitative study.
    PLoS One. 2025;20:e0332610.
    PubMed         Abstract available
    
    
22. DOMINGUES RMSM, Herzog RSA, Dias MAB, Francisco RPV, et al
    Effects of human development, primary care coverage and the COVID-19 pandemic on the fertility rate among adolescents in Brazil in the period 2012-2021.
    PLoS One. 2025;20:e0327656.
    PubMed         Abstract available
    
    
23. GUO L, Jiang L, Huang H
    A longitudinal study of four-year changes in physical fitness among university students before and after COVID-19: 2019-2022.
    PLoS One. 2025;20:e0334088.
    PubMed         Abstract available
    
    
24. BEAUCHAMP M, Farley C, Kirkwood R, Jones A, et al
    Functional recovery 2-years after hospitalization for COVID-19: Insights from the COREG-FR extension study.
    PLoS One. 2025;20:e0334212.
    PubMed         Abstract available
    
    
25. LEE R, Cho J, Bae D, Albers L, et al
    Prospective associations of COVID-related stress with vaping nicotine and cannabis among high school students: Mediated by vaping susceptibility.
    PLoS One. 2025;20:e0334159.
    PubMed         Abstract available
    
    
26. AXEN I, Weiss N, Skillgate E
    Health aspects and lifestyle of licensed manual therapists during the COVID-19 pandemic in Sweden: The CAMP cohort study.
    PLoS One. 2025;20:e0327600.
    PubMed         Abstract available
    
    
27. CHESENG A, Vattanasit U, Kongpran J, Thanapop C, et al
    Environmental health management in local community isolation facilities during COVID-19 pandemic: A case study in Nakhon Si Thammarat, Thailand.
    PLoS One. 2025;20:e0333638.
    PubMed         Abstract available
    
    
28. NGO VK, Vu TT, Sunseri V, Sharma S, et al
    Community's perceptions of the police during COVID-19 in Harlem, New York, a predominantly Black community: Social and geographical dimensions.
    PLoS One. 2025;20:e0329027.
    PubMed         Abstract available
    
    
29. AUSTIN LC, Gomes MN, Chavez S, Degano C, et al
    Foundations under pressure: Qualitative interviews on the impact of prolonged pandemic and public health measures on Ontario youth and young adults.
    PLoS One. 2025;20:e0307423.
    PubMed         Abstract available
    
    

    
    Proc Natl Acad Sci U S A

30. MCKELLAR J, Cadenes J, Garcia de Gracia F, Aube C, et al
    Human MX1 orchestrates the cytoplasmic sequestration of neosynthesized influenza A virus vRNPs.
    Proc Natl Acad Sci U S A. 2025;122:e2418935122.
    PubMed         Abstract available
    
    
31. LIU S, Yan L, Du W, Liu W, et al
    Manifold-constrained nucleus-level denoising diffusion model for structure-based drug design.
    Proc Natl Acad Sci U S A. 2025;122:e2415666122.
    PubMed         Abstract available
    
    

    
    Vaccine

32. ROMANOVA J, Krokhin A, Ferko B, Pleimes D, et al
    Protective efficacy of the UniFluVec influenza vaccine vector against the highly pathogenic influenza A/Indonesia/5/2005 (H5N1) strain in ferrets.
    Vaccine. 2025;65:127795.
    PubMed         Abstract available
    
    
33. ANDERSON KM, Nowak GJ, Cacciatore MA, Rohani P, et al
    Understanding influenza vaccination attitudes and behaviors: An assessment of health decision-making preferences.
    Vaccine. 2025;65:127804.
    PubMed         Abstract available
    
    
34. ALMEIDA GG, Pinto JA, Pinto PM, da Silva LB, et al
    Safety and immunogenicity of SpiN-Tec, a T-cell based RBD-Nucleocapsid chimeric vaccine for COVID-19.
    Vaccine. 2025;64:127756.
    PubMed         Abstract available
    
    
35. HUMPHREYS J, Blake A, Nicolay N, Braeye T, et al
    Effectiveness of JN.1 monovalent COVID-19 vaccination in EU/EEA countries between October 2024 and January 2025: a VEBIS electronic health record network study.
    Vaccine. 2025;64:127752.
    PubMed         Abstract available
    
    
36. CUYPERS L, Dambre C, Desmet S
    Exceptional high number of IPD cases in winter season 2024-2025 in Belgium in concomitance with rise in vaccine serotypes.
    Vaccine. 2025;64:127763.
    PubMed         Abstract available
    
    
37. INOUE S, Fuji K
    The mutual cyclical influence of internet information and vaccination intention on post-dissemination vaccination: A longitudinal study during the availability period of COVID-19 booster shots.
    Vaccine. 2025;64:127741.
    PubMed         Abstract available
    
    
38. HAMONIC G, Pastural E, Arora S, Lew J, et al
    Safety and immunogenicity of COVAC-2, a Sepivac SWE adjuvanted SARS-CoV-2 recombinant protein vaccine in healthy adults; a randomized controlled first-in-human dose-escalation trial.
    Vaccine. 2025;64:127748.
    PubMed         Abstract available
    
    
39. TURJEMAN A, Shochat T, Drozdinsky G, Leibovici L, et al
    Disparities and temporal trends in pneumococcal vaccination uptake among older adults in the Israeli population: A population-based retrospective cohort study.
    Vaccine. 2025;64:127765.
    PubMed         Abstract available
    
    
40. VAN BEEK LF, He X, Koks MS, van der Gaast-de Jongh CE, et al
    Comparing the immunogenicity of intradermal and intramuscular vaccination of elderly with BNT162b2 XBB.1.5: An equivalent dose study.
    Vaccine. 2025;64:127749.
    PubMed         Abstract available
    
    
41. HUANG W, Xu M, Diao Z, Chen J, et al
    Vaccination coverage by age 24 months among children born in 2020 and 2021 in China, during the COVID-19 pandemic: A study based on the national immunization information system.
    Vaccine. 2025;64:127717.
    PubMed         Abstract available
    
    
42. YANG Y, Jin SW, Lee S, Lartey S, et al
    Understanding vaccine willingness in post-COVID America: Key determinants and demographic differences.
    Vaccine. 2025;64:127740.
    PubMed         Abstract available
    
    
43. WETZKE M, Lange M, Beinhauer K, Rope E, et al
    Immunization acceptance after broad recommendation for RSV prophylaxis: Results from a cross-sectional study in Germany.
    Vaccine. 2025;64:127716.
    PubMed         Abstract available
    
    
44. DIEMERT DJ, Graciaa DS, Zhang B, Rouphael NG, et al
    Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial.
    Vaccine. 2025;64:127718.
    PubMed         Abstract available
    
    
45. BALMUTH A, Brennan T, Ashebir S, D'Ambrosio L, et al
    Examining the contributions of demographic variables to vaccination uptake among the U.S. aged 50.
    Vaccine. 2025;64:127711.
    PubMed         Abstract available
    
    
46. WANG Y, Ni Y, Leung CMC, Ning K, et al
    Longitudinal patterns and predictors of COVID-19 vaccine confidence from pre-vaccine rollout to mass vaccination: A population-based cohort study.
    Vaccine. 2025;64:127736.
    PubMed         Abstract available
    
    
47. ZHAO Y, Zhao Z, Cheng C, Tian M, et al
    A bivalent SARS-CoV-2 subunit vaccine for cats neutralizes both the original ancestral strain and BA.1 Pseudovirus carrying the 453F and 501 T mutation.
    Vaccine. 2025;64:127685.
    PubMed         Abstract available
    
    
48. MUES KE, Zhou CK, Gerber JE, van Hunsel F, et al
    A review of methodologic & data considerations for vaccine safety surveillance in the wake of the COVID-19 pandemic.
    Vaccine. 2025;64:127691.
    PubMed         Abstract available
    
    
49. BOGA DJ, Robinson M, Tirupathi M, Juste RS, et al
    Latent class and time-to-event analyses of social determinants of health and COVID-19 vaccine uptake among Black women living with HIV.
    Vaccine. 2025;64:127649.
    PubMed         Abstract available
    
    
50. ROY DN, Rashid M, Aktar A, Parvin MS, et al
    Potential predictors of COVID-19 booster vaccine confidence among adult people: a cross-sectional analysis amid the Omicron surge in Southern Bangladesh.
    Vaccine. 2025;64:127693.
    PubMed         Abstract available

#Antiviral efficacy of oral #ensitrelvir versus oral ritonavir-boosted #nirmatrelvir in #COVID19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial

 

Summary

Background

Ensitrelvir is an oral antiviral treatment for COVID-19 with the same molecular target (the main protease) as ritonavir-boosted nirmatrelvir—the current oral first-line treatment. We aimed to compare the clinical antiviral effects of the two drugs.

Methods

In an open-label, phase 2, randomised, controlled, adaptive pharmacometric platform trial, low-risk adult outpatients aged 18–60 years with early symptomatic COVID-19 (<4 days of symptoms) were recruited from hospital acute respiratory infection clinics in Thailand and Laos. Patients were randomly assigned in blocks (block sizes depended on the number of interventions available) to one of eight treatment groups, including oral ensitrelvir and oral ritonavir-boosted nirmatrelvir at standard doses, both given for 5 days, and no study drug. The primary endpoint was the oropharyngeal SARS-CoV-2 viral clearance rate assessed between day 0 and day 5 in the modified intention-to-treat population (defined as patients with at least 2 days of follow-up). Patients had four oropharyngeal swabs taken on day 0 and two swabs taken daily from days 1 to 7, then on days 10 and 14. Viral clearance rates were derived under a Bayesian hierarchical linear model fitted to log10 viral densities in standardised paired oropharyngeal swab eluates taken daily over the 5 days (14 samples). An individual patient data meta-analysis of all small molecule drugs evaluated in this platform trial using published results was also performed, adjusting for temporal trends in viral clearance. This trial is registered at ClinicalTrials.gov, NCT05041907.

Findings

Between March 17, 2023, and April 21, 2024, 604 of 903 patients enrolled were concurrently assigned to the three treatment groups (ensitrelvir n=202; ritonavir-boosted nirmatrelvir n=207; no study drug n=195). Median estimated SARS-CoV-2 clearance half-lives were 5·9 h (IQR 4·0–8·6) with ensitrelvir, 5·2 h (3·8–6·6) with nirmatrelvir, and 11·6 h (8·1–14·5) with no study drug. Viral clearance following ensitrelvir was 82% faster (95% credible interval 61–104) than no study drug and 16% slower (5–25) than ritonavir-boosted nirmatrelvir. In the meta-analysis of all unblinded small molecule drugs evaluated in the platform trial, nirmatrelvir and ensitrelvir had the largest antiviral effects (1157 patients). Viral rebound occurred in 15 (7%) of 207 patients in the nirmatrelvir group and 10 (5%) of 202 in the ensitrelvir group (p=0·45).

Interpretation

Both ensitrelvir and nirmatrelvir accelerate oropharyngeal SARS-CoV-2 viral clearance. Ensitrelvir is an effective alternative to currently available antivirals in treating COVID-19. Although COVID-19 is now generally a mild disease, it still causes substantial morbidity, particularly in vulnerable groups, and new variants or other coronaviruses could still emerge with pandemic potential. Safe effective and affordable antivirals are needed, and these are best assessed initially in pharmacometric platform trials assessing viral clearance.

Funding

Wellcome Trust through the COVID-19 Therapeutics Accelerator.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00482-7/fulltext?rss=yes

____

History of Mass Transportation: A Henschel & Son 1936 Steam Locomotive

 

By Dornicke - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=5162139

Source: Wikipedia, https://en.wikipedia.org/wiki/Henschel_%26_Son

____

#Assessment of #malnutrition in preschool-aged #children by mid-upper arm circumference in the #Gaza Strip (January, 2024–August, 2025): a longitudinal, cross-sectional, surveillance study

 

Summary

Background

Since October, 2023, Palestinian children in the Gaza Strip have suffered war-induced displacement, food insecurity, malnutrition, and elevated risks of famine and mortality. In this study, we aimed to document the extent of, and patterns in, wasting malnutrition in children aged 6–59 months across the Gaza Strip between January, 2024, and August, 2025.

Methods

This longitudinal, cross-sectional, surveillance study was conducted across a total of 16 UN Relief and Works Agency for Palestine Refugees in the Near East health centres and 78 medical points established within school shelters and tent encampments across the five governorates of Gaza. Children aged 6–59 months were screened for wasting malnutrition by mid-upper arm circumference (MUAC) measurement. Children with a MUAC of less than 125 mm were enrolled into therapeutic feeding regimens. MUAC Z scores were derived from published WHO age-specific and sex-specific arm circumferential growth curves. Monthly prevalence of acute wasting (MUAC Z scores less than –2) and severe wasting (MUAC Z scores less than –3) were described by age, sex, type of screening facility, and governorate.

Findings

Between Jan 1, 2024, and Aug 15, 2025, 265 974 measurements were obtained from 219 783 uniquely identified children, with two-thirds of children screened in Khan Younis and Middle Governorates. The monthly prevalence of acute wasting ranged from 5% (34 of 722 children) to 7% (794 of 10 907) between January and June, 2024. After approximately 4 months of severe aid restrictions between September, 2024, and mid-January, 2025, the prevalence of wasting increased from 8·8% (1601 of 18 225 children) to 14·3% (1661 of 11 619), with the highest prevalence observed in Rafah (32·2%; 95 of 295) and among children aged 24–59 months (21·0%; 1366 of 6518). After a 6-week ceasefire, marked by a substantial increase in the number of aid trucks entering through territory borders, by March, 2025, the prevalence of wasting had declined to 5·5% (831 of 15 165). However, after an 11-week blockade from March to May, 2025, and continued severely restricted entry of food, water, medicines, fuel, and other essentials thereafter, by early August, 2025, 15·8% (1213 of 7668) of screened children were acutely wasted, including 3·7% (280 of 7668) severely wasted, equating to more than 54 600 children in need of therapeutic care.

Interpretation

After nearly 2 years of war and severe restrictions in humanitarian aid, tens of thousands of preschool-aged children in the Gaza Strip are suffering from preventable acute malnutrition and facing an increased risk of mortality.

Funding

UN Relief and Works Agency for Palestine Refugees in the Near East.

Source: The Lancet, https://www.sciencedirect.com/science/article/abs/pii/S0140673625018203?dgcid=rss_sd_all

____

#Italy, Integrated #WNV & #USUV #Surveillance - Weekly Bulletin No. 13, 9 October 2025 (Summary): 22 new confirmed cases

{Summary}

-- During current epidemiological week, a rise in the West Nile Virus human cases has been observed although with reduced intensity compared most recent weeks. 

-- Twenty-two new confirmed human cases have been reported during surveillance week from 2 to 8 October 2025. 

-- The cumulative number of cases rose to 740 (they were 718 last week), of these: 

- 354 were West Nile Neuroinvasive Disease (WNND): 16 in Piedmont, 53 Lombardy, 33 Veneto, 4 Friuli-Venezia Giulia, 1 Liguria, 30 Emilia-Romagna, 11 Tuscany, 1 Marche, 84 Latium, 2 Molise, 81 Campania, 2 Apulia, 2 Basilicata, 5 Calabria, 3 Sicily, 26 Sardinia,

- 57 were asymptomatic cases in blood donors, 

- 318 were West Nile Fever cases, of which 1 imported from Kenya, 1 from Egypt and 1 from Maldives, 

- 4 asymptomatic cases, 

- 7 unspecified cases. 

-- Among confirmed cases there were 68 fatalities: 7 in Piedmont, 9 Lombardy, 2 Emilia-Romagna, 18 Latium, 28 Campania, 2 Calabria, 1 Sicily, 1 Sardinia. 

- The Case-Fatality Rate in WNND cases is now at 19.2% (it was 20% in 2018 and 14% in 2024). 

-- During current epidemic season, ten Usutu Virus human cases have been confirmed: 2 in Piedmont, 3 Lombardy, 2 Veneto, 3 Latium.

(...)

Source: High Institute of Health, https://www.epicentro.iss.it/westnile/bollettino/Bollettino_WND_2025_13.pdf

____

#Bulgaria - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 

A poultry farm in Haskovo Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6861

____

#Netherlands - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 

On 6 October 2025, an outbreak of H5 was confirmed on a breeding poultry farm in Gasselternijveenschemond, a 3 km protection zone and a 10 km surveillance zone have been established. In the 3 km zone there are 6 other poultry premises. The poultry farms in the 3 km zone have been screened (examined, sampled and tested) and results coming in next follow up report. The subtype HPAI H5 is confirmed by the national reference laboratory (NRL). All susceptible animals on the infected premise have been killed.

Source: WOAH, https://wahis.woah.org/#/in-review/6856

____

#Denmark - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 

The Danish Veterinary and Food Administration has established a 3 km and 10 km zone around the poultry holding and is implementing the necessary measures in accordance with the European Union Animal Health Law.

On 6 October 2025 a clinical suspicion was reported to the Danish Veterinary and Food Administration. The affected poultry holding consists of 150000 laying hens. On 7 October 2025 highly pathogenic avian influenza sub. H5N1 was confirmed by the national reference laboratory. A 3 km protection zone and a 10 km surveillance zone has been established. The culling is planned to be initiated on 8 October 2025.

Source: WOAH, https://wahis.woah.org/#/in-review/6858

____

Molecular divergence and #convergence of mammalian #antibody responses to the #influenza virus #hemagglutinin stem

 

Significance

Since pigs serve as intermediate hosts between humans and the natural reservoir of influenza viruses in wild birds, they play a key role in the emergence of influenza strains with pandemic potential, as demonstrated by the 2009 pandemic. Therefore, influenza pandemic preparedness will benefit from the development of vaccines that broadly protect pigs against diverse influenza A strains. However, progress is limited by our poor molecular understanding of porcine antibody responses to influenza virus. This study isolates and characterizes a panel of broadly neutralizing influenza antibodies from pigs. Our findings not only have significant implications for the development of broadly protective influenza vaccines for pigs, but also reveal the molecular differences in the antibody responses between pigs and humans.

Abstract

Antibody responses to the influenza virus hemagglutinin (HA) stem, a major target for broadly protective vaccine development, have been extensively characterized in humans. However, they remain largely elusive in other natural influenza hosts, including pigs, which are considered intermediate hosts for the emergence of pandemic strains. By leveraging single-cell variable, diversity, and joining (VDJ) sequencing, this study identified 25 porcine antibodies to the HA stem, including two cross-group bnAbs, 14-8 and 15-1, from vaccinated specific-pathogen-free pigs and unvaccinated domestic pigs. Cryogenic electron microscopy analysis showed that 14-8 targeted the well-characterized central stem epitope, whereas 15-1 bound to a linear epitope spanning the HA1/HA2 junction. Additionally, while some porcine and human bnAbs targeted the central stem epitope via convergent molecular signatures, our results revealed a pig-specific recurring binding motif. Overall, our findings provide important insights into the commonalities and uniqueness of antibody responses between different species, which have significant implications for vaccine development for nonhuman animals.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/abs/10.1073/pnas.2510927122?af=R

____

Molecular basis of #SARS-CoV-2 proofreading enzyme–mediated #resistance to #remdesivir

 

Abstract

SARS-CoV-2’s remarkable resistance to nucleotide analog antivirals such as remdesivir, which thwarts RNA synthesis by inhibiting viral polymerase (RdRp), challenges available therapies. We reveal that remdesivir incorporation destabilizes RdRp–RNA complex while enhancing RNA binding to the proofreading exoribonuclease (ExoN), facilitating remdesivir excision. Conserved ExoN determinants for remdesivir recognition and excision underpin ExoN-mediated resistance across all coronaviruses. These findings inform the design of next-generation antivirals and combination therapies capable of overcoming ExoN-mediated resistance.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/full/10.1073/pnas.2519755122

____

Association of 2024–2025 #Covid19 #Vaccine with Covid-19 #Outcomes in #US #Veterans

 

Abstract

Background

Amid the declining clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and diminishing public uptake of annual coronavirus disease 2019 (Covid-19) vaccines, contemporary evidence on vaccine effectiveness against clinically relevant outcomes is needed.

Methods

We conducted an observational study that used the electronic health records of the Department of Veterans Affairs to evaluate the effectiveness of the 2024–2025 Covid-19 vaccine among veterans who received the Covid-19 and influenza vaccines on the same day (164,132 participants) and in an active-comparator group of veterans who received the influenza vaccine only (131,839 participants), between September 3 and December 31, 2024. Participants were followed for 180 days or until the occurrence of an outcome, whichever came first. We used inverse-probability–weighted models to estimate vaccine effectiveness (calculated as 1 minus the risk ratio) against Covid-19–associated emergency department visits, hospitalizations, and deaths at 6 months.

Results

At 6 months of follow-up, the estimated vaccine effectiveness was 29.3% (95% confidence interval [CI], 19.1 to 39.2) against Covid-19–associated emergency department visits (risk difference per 10,000 persons, 18.3; 95% CI, 10.8 to 27.6), 39.2% (95% CI, 21.6 to 54.5) against Covid-19–associated hospitalizations (risk difference per 10,000 persons, 7.5; 95% CI, 3.4 to 13.0), and 64.0% (95% CI, 23.0 to 85.8) against Covid-19–associated deaths (risk difference per 10,000 persons, 2.2; 95% CI, 0.5 to 6.9). Vaccine effectiveness against a composite of these outcomes was 28.3% (95% CI, 18.2 to 38.2), with a risk difference per 10,000 persons of 18.2 (95% CI, 10.7 to 27.5). The Covid-19 vaccine was associated with decreased risks of these outcomes across prespecified subgroups defined according to age (<65 years, 65 to 75 years, and >75 years), the presence or absence of major coexisting conditions, and immunocompetence status.

Conclusions

In this national cohort of U.S. veterans, the receipt of the 2024–2025 Covid-19 vaccine was associated with decreased risks of severe clinical outcomes. (Funded by the Department of Veterans Affairs.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2510226?query=TOC

____

#India - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=116380120}

Nineteen captive Painted Storks in the National Zoological Park, Delhi.

Source: WOAH, https://wahis.woah.org/#/in-review/6803

____

Comparative #risk #assessment of highly pathogenic avian #influenza #H5 viruses spread in French #broiler and layer sectors

 

Abstract

Since 2015, French poultry production is threatened almost every year by a reintroduction of highly pathogenic avian influenza H5 viruses. The duck sector was the most concerned by this crisis but other sectors such as broiler, layer and turkey were also affected by outbreaks. The objective of this work was to assess the risk of highly pathogenic avian influenza H5 virus transmission from one farm to another within the French broiler and layer production network. This study used the WOAH risk assessment framework. After drawing up a scenario tree of virus transmission from one farm to another, data were collected through a literature review or through experts elicitation. Three questionnaires were developed according to the experts field of expertise: avian influenza, broiler and layer sectors. The experts estimates were combined using a beta distribution weighted by their confidence level. A Monte Carlo iteration process was used to combine the different probabilities of the scenario tree and to assess the transmission risk. In the broiler sector, the highest transmission probabilities were observed if the exposed farm was an indoor broiler farm and the source a broiler farm (indoor or free-range). The high transmission probability between broiler farms integrated within the same association suggests that integration is an important risk factor. Person movement, transport of feed and manure management were the pathways with the highest transmission probabilities between two integrated indoor broiler farms with good biosecurity levels. In the layer sector, the highest transmission probabilities were observed if the source farm was a free-range farm and the exposed farm a production farm (indoor or free-range). The pathways with the highest transmission probabilities were egg transport and person movement. The sensitivity analysis showed that the exposed farm's biosecurity had a significant impact on the transmission probability. Our results provide an insight on the role of each type of farms in the virus spread within the French broiler and layer production sectors and will be useful for the implementation of control measures such as movement restriction or vaccination.

Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.09.11.612235v5

____

Maternal #Influenza A Virus #Infection Induces Antiviral and Immune Dysregulation in the #Placenta and #Fetus Without Vertical Transmission

 

Abstract

Influenza A virus (IAV) infection during pregnancy is associated with stillbirth and preterm birth, possibly by disrupting placental and fetal immunity. To investigate this, pregnant pigtail macaques were inoculated with IAV [A/California/07/2009 (H1N1)] and examined at necropsy 5 days post-infection (N=11) versus uninfected controls (N=16). Stillbirth occurred in 18% of infected pregnancies but not in controls. While vertical transmission was not observed, low levels of viral RNA were detected in two placentas. Maternal IAV infection was associated with increased placental IL-1β and IFN-β levels and an upregulated type I interferon and integrated stress transcriptional response. Fetuses exposed to IAV had greater frequencies of innate immune cells in lymph nodes and CD4+ T cells in lungs. These results suggest that placental and fetal immune environments undergo immune activation independent of the severity of maternal lung infection. Influenza vaccination during pregnancy may protect against potentially harmful effects on fetal development.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institutes of Health, https://ror.org/01cwqze88, AI164588, AI176777, AI007509

Foundation for the National Institutes of Health, https://ror.org/00k86s890, OD010425, TR002318, GM007266, OD011123

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.10.06.675688v1

____

#Iran - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 

A backyard village poultry in Ardebil Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6849

____

#Poland - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 

{By JJ Harrison - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5014480}

A slaugthter geese farm in Wielkopolskie Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6852

____