Saturday, May 3, 2025

Introducing a #framework for within-host #dynamics and #mutations modelling of #H5N1 #influenza infection in #humans

Abstract

Avian influenza A(H5N1) poses a public health risk due to its pandemic potential should the virus mutate to become human-to-human transmissible. To date, reported influenza A(H5N1) human cases have typically occurred in the lower respiratory tract with a high case fatality rate. There is prior evidence of some influenza A(H5N1) strains being a small number of amino acid mutations away from achieving droplet transmissibility, possibly allowing them to be spread between humans. We present a mechanistic within-host influenza A(H5N1) infection model, novel for its explicit consideration of the biological differences between the upper and lower respiratory tracts. We then estimate a distribution of viral lifespans and effective replication rates in human H5N1 influenza cases. By combining our within-host model with a viral mutation model, we determine the probability of an infected individual generating a droplet transmissible strain of influenza A(H5N1) through mutation. For three mutations, we found a peak probability of approximately 10-3 that a human case of H5N1 influenza produces at least one virion during the infectious period. Our findings provide insights into the risk of differing infectious pathways of influenza A(H5N1) (namely avian-human vs avian-mammal-human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.09.01.24312235v4

____

#Coronavirus Disease Research #References (by AMEDEO, May 3 '25)

 


    Ann Intern Med

  1. BILINSKI A, Emanuel N, Ciaranello A
    Sins of Omission: Model-Based Estimates of the Health Effects of Excluding Pregnant Participants From Randomized Controlled Trials.
    Ann Intern Med. 2025 Apr 29. doi: 10.7326/ANNALS-24-00689.
    PubMed         Abstract available

  2. YEK C, Mancera AG, Diao G, Walker M, et al
    Impact of the COVID-19 Pandemic on Antibiotic Resistant Infection Burden in U.S. Hospitals : Retrospective Cohort Study of Trends and Risk Factors.
    Ann Intern Med. 2025 Apr 29. doi: 10.7326/ANNALS-24-03078.
    PubMed         Abstract available

  3. RIDDLER SA, Moodie Z, Clark J, Yen C, et al
    High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302).
    Ann Intern Med. 2025 Apr 29. doi: 10.7326/ANNALS-24-02701.
    PubMed         Abstract available

  4. KIM D, Danpanichkul P, Wijarnpreecha K, Cholankeril G, et al
    Trends in Mortality From Chronic Liver Disease Before, During, and After the COVID-19 Pandemic, 2015 to 2023.
    Ann Intern Med. 2025 Apr 29. doi: 10.7326/ANNALS-24-03218.
    PubMed        


    BMJ

  5. YUEN ASC, Chen B, Chan AYL, Hayes JF, et al
    Use of gabapentinoid treatment and the risk of self-harm: population based self-controlled case series study.
    BMJ. 2025;389:e081627.
    PubMed         Abstract available


    Clin Infect Dis

  6. CHRISTENSEN A, Nelson Z, Gustafson S, Stoecker R, et al
    Into the Unknown: Practical Remdesivir Restriction in the Era of Widespread SARS-CoV-2 Seropositivity.
    Clin Infect Dis. 2025 Apr 25:ciaf217. doi: 10.1093.
    PubMed         Abstract available

  7. JONES KM, Greene MT, Meddings J, Mantey J, et al
    Impact of a Collaboration-Focused Intervention to Prevent Healthcare-Associated Infections Before and During the Coronavirus Disease 2019 Pandemic.
    Clin Infect Dis. 2025 Apr 29:ciaf122. doi: 10.1093.
    PubMed         Abstract available


    Emerg Infect Dis

  8. SPENCER BR, Akinseye A, Grebe E, Stone M, et al
    Self-Reported SARS-CoV-2 Infections among National Blood Donor Cohort, United States, 2020-2022.
    Emerg Infect Dis. 2025;31:1006-1009.
    PubMed         Abstract available

  9. GREBE E, Chacreton D, Stone M, Spencer BR, et al
    Detection of SARS-CoV-2 Reinfections Using Nucleocapsid Antibody Boosting.
    Emerg Infect Dis. 2025;31:958-966.
    PubMed         Abstract available


    Infect Control Hosp Epidemiol

  10. NGAI V, Hsi JB, Singh RD, Mitchell JE, et al
    COVID-19 prevention training with video-based feedback in nursing homes: impact on staff safety behaviors.
    Infect Control Hosp Epidemiol. 2025 Apr 28:1-8. doi: 10.1017/ice.2025.
    PubMed         Abstract available


    Intensive Care Med

  11. PETTENUZZO T, Balzani E, Sella N, Giani M, et al
    Prone positioning during veno-venous extracorporeal membrane oxygenation: a systematic review and meta-analysis.
    Intensive Care Med. 2025 Apr 29. doi: 10.1007/s00134-025-07877.
    PubMed         Abstract available

  12. ESPERATTI M, Fuentes N, Olmos M
    Optimizing non-intubated respiratory support in COVID-19: evaluating the impact of bundle of care strategy on awake prone positioning tolerance. Author's reply.
    Intensive Care Med. 2025 Apr 29. doi: 10.1007/s00134-025-07904.
    PubMed        


    J Infect

  13. DAHL TB, Aftab F, Prebensen C, Berdal JE, et al
    Imidazole propionate is increased in severe COVID-19 and correlates with cardiac involvement.
    J Infect. 2025;90:106494.
    PubMed        

  14. OVERTON CE, Fyles M, Mellor J, Paton RS, et al
    SARS-CoV-2 test sensitivity and duration of positivity in the UK during the 2023/2024 Winter: A prospective cohort study based on self-reported data.
    J Infect. 2025;90:106485.
    PubMed         Abstract available


    J Med Virol

  15. MESSALI S, Bertelli A, Dotta L, Giovanetti M, et al
    Outbreak of Enterovirus D68 in Young Children, Brescia, Italy, August to November 2024.
    J Med Virol. 2025;97:e70372.
    PubMed         Abstract available

  16. TRIFONOV G, Buscher E, Fistera D, Kill C, et al
    Disease Burden of RSV Infection in Adult Patients in Comparison to Influenza Virus Infection.
    J Med Virol. 2025;97:e70373.
    PubMed         Abstract available


    J Virol

  17. SUN H, Yang Q, Zhang Y, Cui S, et al
    Syntaxin-6 restricts SARS-CoV-2 infection by facilitating virus trafficking to autophagosomes.
    J Virol. 2025 Apr 25:e0000225. doi: 10.1128/jvi.00002.
    PubMed         Abstract available

  18. NEGI V, Kuhn RJ
    A BSL-2 chimeric system designed to screen SARS-CoV-2 E protein ion channel inhibitors.
    J Virol. 2025 Apr 30:e0225224. doi: 10.1128/jvi.02252.
    PubMed         Abstract available

  19. ZHANG S, Xu C-L, Wang J, Xiong X, et al
    Spike proteins of coronaviruses activate mast cells for degranulation via stimulating Src/PI3K/AKT/Ca(2+) intracellular signaling cascade.
    J Virol. 2025 Apr 30:e0007825. doi: 10.1128/jvi.00078.
    PubMed         Abstract available


    JAMA

  20. KIANG MV, Bubar KM, Maldonado Y, Hotez PJ, et al
    Modeling Reemergence of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination in the US.
    JAMA. 2025 Apr 24. doi: 10.1001/jama.2025.6495.
    PubMed         Abstract available


    Nature

  21. WANG N, Ji W, Jiao H, Veit M, et al
    A MERS-CoV-like mink coronavirus uses ACE2 as entry receptor.
    Nature. 2025 Apr 30. doi: 10.1038/s41586-025-09007.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, May 3 '25)

 


    Arch Virol

  1. SVYATCHENKO SV, Boldyrev ND, Panova AS, Kolosova NP, et al
    Seroprevalence of anti-influenza antibodies in humans and characterization of seasonal influenza viruses isolated in Russia during the 2023-2024 flu season.
    Arch Virol. 2025;170:118.
    PubMed         Abstract available


    Biochem Biophys Res Commun

  2. CHU X, Yang Y, Guo H, Ji X, et al
    SARS-CoV-2 NSP2 specifically interacts with cellular protein SmgGDS.
    Biochem Biophys Res Commun. 2025;764:151828.
    PubMed         Abstract available

  3. ZHANG YH, Su AM, Hou XM
    Structural and functional insights into the SARS-CoV-2 SUD domain and its interaction with RNA G-Quadruplexes.
    Biochem Biophys Res Commun. 2025;764:151817.
    PubMed         Abstract available


    Epidemiol Infect

  4. STERIAN M, Naganathan T, Corrin T, Waddell L, et al
    Evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition: an updated living systematic review.
    Epidemiol Infect. 2025;153:e62.
    PubMed         Abstract available


    J Gen Virol

  5. ARANDA AJ, Aguilar-Tipacamu G, Perez DR, Banuelos-Hernandez B, et al
    Emergence, migration and spreading of the high pathogenicity avian influenza virus H5NX of the Gs/Gd lineage into America.
    J Gen Virol. 2025;106:002081.
    PubMed         Abstract available


    J Infect

  6. CARSTENS G, Kozanli E, Bulsink K, McDonald S, et al
    Co-infection dynamics of SARS-CoV-2 and respiratory viruses in the 2022/2023 respiratory season in the Netherlands.
    J Infect. 2025 Mar 21:106474. doi: 10.1016/j.jinf.2025.106474.
    PubMed         Abstract available

  7. WARD T, Paton RS, Overton CE, Mellor J, et al
    Understanding the Effectiveness of the Comirnaty Monovalent and Bivalent Vaccines During the Winter Coronavirus (COVID-19) Infection Survey.
    J Infect. 2025 Mar 5:106461. doi: 10.1016/j.jinf.2025.106461.
    PubMed         Abstract available


    Pediatrics

  8. LOVEDAY T, da Hora C, Wells R, Chorny L, et al
    11-Year-Old Boy With B-ALL-Induced Hypereosinophilic Syndrome Presenting as Acute Encephalopathy.
    Pediatrics. 2025;155:e2024068064.
    PubMed         Abstract available

  9. BAHADIR Z, Narayan P, Wolters R, Permar SR, et al
    Monoclonal Antibodies for Pediatric Viral Disease Prevention and Treatment.
    Pediatrics. 2025;155:e2024068690.
    PubMed         Abstract available

  10. ZHANG L, Wang Y, Berger LM
    State-Based Eviction Moratoria and Child Maltreatment During the COVID-19 Pandemic.
    Pediatrics. 2025;155:e2024068174.
    PubMed         Abstract available

  11. BANDELL A, Giles L, Cervelo Bouzo P, Sibbring GC, et al
    Safety of LAIV Vaccination in Asthma or Wheeze: A Systematic Review and GRADE Assessment.
    Pediatrics. 2025 Apr 24:e2024068459. doi: 10.1542/peds.2024-068459.
    PubMed         Abstract available


    PLoS Biol

  12. KUBINSKI HC, Despres HW, Johnson BA, Schmidt MM, et al
    Variant mutation G215C in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.
    PLoS Biol. 2025;23:e3003115.
    PubMed         Abstract available


    PLoS Comput Biol

  13. HODCROFT EB, Wohlfender MS, Neher RA, Riou J, et al
    Estimating Re and overdispersion in secondary cases from the size of identical sequence clusters of SARS-CoV-2.
    PLoS Comput Biol. 2025;21:e1012960.
    PubMed         Abstract available


    PLoS One

  14. WITEK TJ JR, Sheikhan NY, Tran A
    Sensory effects of COVID-19 in wine professionals.
    PLoS One. 2025;20:e0321502.
    PubMed         Abstract available

  15. MARSIGLIA MD, Bianchi S, Bai F, Tincati C, et al
    Effectiveness of Anti-SARS-CoV-2 monoclonal antibodies in real-life: RNAemia and clinical outcomes in high-risk COVID-19 patients.
    PLoS One. 2025;20:e0321356.
    PubMed         Abstract available

  16. VANOUDENHOVE J, Liu Y, Nelakanti R, Kim D, et al
    Impact of memory T cells on SARS-CoV-2 vaccine response in hematopoietic stem cell transplant.
    PLoS One. 2025;20:e0320744.
    PubMed         Abstract available

  17. GHIROTTO L, De Panfilis L, Perin M, Miraglia Raineri A, et al
    Psycho-oncology practice for cancer patients during the pandemic lockdown in Italy: A qualitative mixed-method study with psychotherapists.
    PLoS One. 2025;20:e0318241.
    PubMed         Abstract available

  18. MOTIEI M, Hassanzadeh Rad A, Badeli H, Bayat R, et al
    Hospitalization dynamics during COVID-19: Insights into disease trends and patient outcomes.
    PLoS One. 2025;20:e0321269.
    PubMed         Abstract available

  19. ROSA S, Pulido MA, Ruiz JJ, Cocucci TJ, et al
    Transmission matrix parameter estimation of COVID-19 evolution with age compartments using ensemble-based data assimilation.
    PLoS One. 2025;20:e0318426.
    PubMed         Abstract available

  20. CHEN Q, Mat Sin NSB, Mohd Isa ANB, Chen D, et al
    Investigation on the association between college students' smartphone-related behaviors and sleep quality during COVID-19.
    PLoS One. 2025;20:e0321060.
    PubMed         Abstract available

  21. LOHINIVA AL, Lehtinen JM, Arifulla D, Ollgren J, et al
    Factors influencing healthcare workers' compliance with personal protective equipment guidelines in long-term care during the COVID-19 pandemic-A theory-based mixed-methods study.
    PLoS One. 2025;20:e0321851.
    PubMed         Abstract available

  22. SCHAEFER CM, Krause TM, Delclos GL, Greenberg RS, et al
    Risk of post-acute symptoms among adults: A comparison study of severe COVID-19, pneumonia, and influenza.
    PLoS One. 2025;20:e0322020.
    PubMed         Abstract available

  23. WU R, He Y, Teng Z
    Energy price instability and energy efficiency: Korea's macroeconomic framework during the COVID-19 pandemic.
    PLoS One. 2025;20:e0321793.
    PubMed         Abstract available

  24. GEBEYEHU DT, East L, Wark S, Islam MS, et al
    Food safety practices of individuals before and after the emergence of COVID-19: A pre- and post-comparative analysis.
    PLoS One. 2025;20:e0322235.
    PubMed         Abstract available

  25. CARPALLO-PORCAR B, Jimenez-Sanchez C, Calvo S, Irun P, et al
    ARACOV-02. Specialized nutritional intervention and telerehabilitation in patients with long COVID: Protocol of a randomized controlled trial.
    PLoS One. 2025;20:e0321811.
    PubMed         Abstract available

  26. OKMI M, Ang TF, Mohd Zaki MF, Ku CS, et al
    Mobile Phone Network Data in the COVID-19 era: A systematic review of applications, socioeconomic factors affecting compliance to non-pharmaceutical interventions, privacy implications, and post-pandemic economic recovery strategies.
    PLoS One. 2025;20:e0322520.
    PubMed         Abstract available

  27. DENNIS A, Joseph J, Greenwell K, Miller S, et al
    A qualitative process evaluation of a nasal spray intervention to prevent respiratory tract infections.
    PLoS One. 2025;20:e0321314.
    PubMed         Abstract available

  28. SHRESTHA S, Jha P, Shrestha L, Chaudhary LB, et al
    Trend of influenza before and during the COVID-19 pandemic in Nepal-A study from 2018 to 2022.
    PLoS One. 2025;20:e0299610.
    PubMed         Abstract available

  29. FARUK MO, Siddik MAB, Chowdhury KUA, Bari N, et al
    Mental health of persons with disabilities during the COVID-19 pandemic in Bangladesh.
    PLoS One. 2025;20:e0322218.
    PubMed         Abstract available

  30. HIRANBURANA N, Thippamom N, Avihingsanon A, Wacharapluesadee S, et al
    Differential immunogenicity in people living with HIV with varying CD4 levels after bivalent mRNA COVID-19 booster vaccination.
    PLoS One. 2025;20:e0317940.
    PubMed         Abstract available


    Proc Natl Acad Sci U S A

  31. GRANULO A, Fuchs C, Bohm R
    Psychological reactance to system-level policies before and after their implementation.
    Proc Natl Acad Sci U S A. 2025;122:e2409907122.
    PubMed         Abstract available

  32. CHI G, Abel GJ, Johnston D, Giraudy E, et al
    Measuring global migration flows using online data.
    Proc Natl Acad Sci U S A. 2025;122:e2409418122.
    PubMed         Abstract available


    Vaccine

  33. SINGLETON KL, Post DJ, Augustine AD, Ison MG, et al
    Collaborative influenza vaccine innovation centers (CIVICs) program.
    Vaccine. 2025;54:127118.
    PubMed         Abstract available

  34. ESSINK BJ, Vermeulen W, Andrade C, de Rooij R, et al
    Corrigendum to 'A randomised phase 2 immunogenicity and safety study of a MF59-adjuvanted quadrivalent subunit inactivated cell-derived influenza vaccine (aQIVc) in adults aged 50 years and older' Vaccine 51 (2025) 126791.
    Vaccine. 2025;56:127127.
    PubMed        

  35. FATIMAH MNN, Thian BYZ, Wong CL, Ong HK, et al
    Chimeric virus-like particles of nodavirus displaying M2e of human and avian influenza A viruses as a potential dual-use vaccine: Inducing a broader immune response and protecting mice against viral infections.
    Vaccine. 2025;56:127165.
    PubMed         Abstract available

  36. BUSTAMANTE Q, Sparkes D, Findlater L, Munro K, et al
    Understanding occupational and attitudinal factors influencing UK healthcare worker decisions for COVID-19 and influenza vaccination: A cross-sectional survey within SIREN.
    Vaccine. 2025;56:127160.
    PubMed         Abstract available

Modeling viral #shedding and #symptom #outcomes in #oseltamivir-treated experimental #influenza infection

Abstract

Influenza remains a global public health concern, and although the antiviral drug oseltamivir is widely used to treat infections, questions regarding its actual antiviral efficacy and clinical benefits remain. Here, we evaluated the effects of oseltamivir on viral shedding dynamics in the context of experimental influenza infection. We analyzed individual participant data, including viral load, time to symptom alleviation, and laboratory test measurements, obtained from three publicly available clinical trials involving experimental infections with influenza A and B viruses. We applied mathematical modeling and estimated parameters using a nonlinear mixed-effects model to capture viral infection dynamics. Our analysis revealed that, compared with placebo groups, the oseltamivir-treated groups tended to have lower values in terms of viral load area under the curve, duration of infection, peak viral titer, and time to peak; however, most of these differences were not significant; and no dose-dependent effects were observed. Moreover, there was no significant correlation between time to symptom alleviation and viral load. Some laboratory test parameters showed opposing correlations with symptom-related and viral load-related outcomes. These findings are consistent with distinct mechanisms underlying the symptom-alleviating effects of oseltamivir and its antiviral activity. Our findings suggest that the availability of individual-level data for public use is essential because it enables the evaluation of mechanisms in clinical trials and the development of more appropriate outcome measures.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.02.651873v1

____

#Pigeons exhibit low susceptibility and poor #transmission capacity for #H5N1 clade 2.3.4.4b high pathogenicity avian #influenza virus

Abstract

The ongoing panzootic of H5N1 high pathogenicity avian influenza virus (HPAIV) has caused the deaths of over half a billion wild birds and poultry, and has led to spillover events in both wild and domestic mammals, alongside sporadic human infections. A key driver of this panzootic is the apparent high viral fitness across diverse avian species, which facilitates an increased interface between wild and domestic species. Columbiformes (pigeons and doves) are commonly found on poultry premises and are highly connected to humans in urban settlements, yet relatively little is known about their potential role in contemporary HPAIV disease ecology. Here we investigated the epidemiological role of pigeons (Columba livia) by determining their susceptibility using decreasing doses of clade 2.3.4.4b H5N1 HPAIV (genotype AB). We investigated infection outcomes and transmission potential between pigeons and to chickens for each dose. Following direct inoculation, pigeons did not develop clinical signs, and only those inoculated with the highest dose shed viral RNA or seroconverted to H5N1-AB, revealing a MID50 of 10^5 EID50. Even in the high dose group, only low-level shedding and environmental contamination was observed, and low-level viral RNA were present in the tissues of directly inoculated pigeons, with no distinct pathological lesions. Pigeons did not transmit the virus to naive pigeons or chickens placed in direct contact. Overall, these findings suggest that pigeons have a low susceptibility to clade 2.3.4.4b H5N1 HPAIV and are less likely to significantly contribute to disease ecology, incursions into poultry, or pose a significant zoonotic threat.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.02.651910v1

____

Friday, May 2, 2025

#US CDC: #Results of #Influenza #Risk Assessment Tool {#IRAT, May 2 '25}



At a glance

-- The Influenza Risk Assessment Tool (IRAT) is a CDC evaluation tool developed with assistance from global animal and human health influenza experts.

-- The IRAT is used to assess the potential pandemic risk of influenza A viruses that are not currently circulating in people.

-- This latest IRAT assessed two recent clade 2.3.4.4b avian influenza A(H5N1) viruses: A/California/147/2024 and A/Washington/239/2024.

-- These viruses scored in the "moderate risk" category for potential emergence and public health impact, similar to previous assessments of earlier clade 2.3.4.4b avian influenza A(H5N1) viruses. These results validate the proactive, coordinated U.S. government response.

-- The IRAT does not assess the immediate risk to the public's health, which is unchanged and remains low, and it does not predict future pandemics.


Purpose

The IRAT uses expert opinion to evaluate the potential of a representative novel influenza A virus to gain the ability for person-to-person spread and the resulting potential public health impact if that were to happen, and it allows for comparison to other viruses evaluated in past IRAT reports. 

The IRAT does not assess the immediate risk to the public's health, and it does not predict future pandemics. 

The immediate risk to the public's health from clade 2.3.4.4b avian influenza A(H5N1) viruses is unchanged and is currently considered to be low

The current H5N1 bird flu situation continues to be mostly an animal health issue. 

Human infections with avian influenza A(H5N1) viruses are rare, and these viruses still are not well-adapted to spreading among people, as they do not currently have the ability to easily infect the human upper respiratory tract. 

Of the 70 cases in the United States from 2024-2025, 41 were associated with exposure to influenza A(H5N1)-infected cattle and 24 were associated with exposure to influenza A(H5N1)-infected poultry/birds. 

In addition, there were two cases with backyard poultry exposure and three cases with unknown exposure

Globally, most past human infections with avian influenza A(H5N1) viruses have occurred following close, unprotected contact with sick or dead birds.

This report summarizes the findings of an IRAT conducted on two viruses that caused recent human illnesses: 

-- A/California/147/2024 

and 

-- A/Washington/239/2024

The resulting score places both of these viruses, representative of two main groups of avian influenza A(H5N1) viruses currently circulating among animals in the United States, in the category of "moderate risk" for potential future emergence and public health impact. This is similar to previous assessments of earlier avian influenza A(H5N1) viruses. The scores for this IRAT were submitted on March 14, 2025.

During a public health response, the IRAT can be used to assess the appropriateness of the ongoing response efforts and whether additional actions are warranted based on the risk score. 

The results of this IRAT validate the proactive, coordinated U.S. government response. Assessing risk is an iterative process with new information being assimilated regularly and response activities adjusted as indicated.


Key findings

On May 2, 2025, CDC published a new IRAT assessment for two clade 2.3.4.4b avian influenza A(H5N1) viruses: A/California/147/2024 and A/Washington/239/2024. 

A/California/147/2024 is a B3.13 genotype virus, like the ones currently circulating in dairy cows in the United States and causing sporadic human infections, mostly among people who had exposure to H5N1 virus-infected or presumed infected dairy cattle. 

A/Washington/239/2024 is a D1.1 genotype virus, like those that are most commonly circulating in wild/migratory birds and also causing poultry outbreaks and sporadic human illnesses, mostly among people who had exposure to poultry confirmed to have influenza A(H5N1) virus infection. The genes of this virus are more closely related to what has been circulating most commonly in U.S. wild birds and poultry.

Previously, CDC assessed three other clade 2.3.4.4b avian influenza A(H5N1) viruses, including A/American wigeon/South Carolina/AH0195145/2021, A/mink/Spain/3691-8_22VIR10586-10/2022, and A/Texas/37/2024. All three previously assessed viruses had overall estimated IRAT scores in the moderate risk category range of 4.0 to 7.9.

This updated assessment includes new information, including information from additional human cases reported in the United States. 

This updated assessment indicates that these two viruses (A/California/147/2024 and A/Washington/239/2024) scored slightly lower in some risk elements and slightly higher in others compared with the previously assessed H5N1 clade 2.3.4.4b viruses. 

However, the mean-high and mean-low acceptable score ranges for these viruses overlap, indicating that these viruses remain similar, and their overall risk scores remain "moderate."

The average risk scores for the potential emergence of the A/California/147/2024 and A/Washington/239/2024 viruses were 5.59 and 5.21, respectively, placing them in the mid-low range of the moderate risk category.

The average risk scores for these two viruses to potentially impact public health was 5.91 and 6.00, respectively, placing them in the mid-range of the moderate risk category.

These scores reflect a decrease of at least 0.20 in the potential emergence question and a decrease of at least 0.09 in the potential public health impact question compared with the previous A/Texas/37/2024 virus evaluation from last year, but both questions on emergence and public health impact still fall into the moderate risk category.

Some variation was seen among subject matter expert (SME) point estimate scores across the risk elements, including Human Infections and Infections in Animals, where the scores ranged from moderate to high risk for the A/California/147/2024 virus, and Disease Severity and Pathogenesis, Global Distribution of Animal Influenza Viruses, and Human Infections for the A/Washington/239/2024 virus. This indicates some uncertainty in interpretation and confidence of the available data.

Sensitivity analyses using the lowest and highest scores for these four risk elements resulted in adjusted ranges for the overall emergence risk and the potential impact risk that continued to place this virus in the mid-range of the moderate risk category. This indicates that the categorization of HPAI A(H5N1) clade 2.3.4.4b virus, including A/California/147/2024 and A/Washington/239/2024, as moderate risk was unchanged by the range of scores within the risk elements exhibiting variation.

The full report is available at Virus Descriptions and Report Summaries.


Background

Input on IRAT assessments is provided by a diverse group of U.S. government animal and human health influenza experts. More information about the IRAT, including a description of its methodology and definitions for its risk elements and categories, is available at Influenza Risk Assessment Tool (IRAT). The IRAT is updated when new zoonotic or novel influenza A viruses with pandemic potential emerge or undergo a change in characteristics that prompts the need for a new assessment.


Summary of U.S. Human Cases of H5 Bird Flu

In the United States since April 2024, 70 human illnesses with H5 bird flu have been reported in 13 states. One additional human case of H5N1 bird flu was reported in the United States in April 2022 in a farm worker who experienced fatigue without any other symptoms and while depopulating poultry at a poultry farm with confirmed avian influenza A(H5N1) virus.


Summary of U.S. human cases associated with dairy cattle exposure

The first human case in the United States associated with the outbreaks of A(H5N1) virus among dairy cattle was reported on April 1, 2024, by the State of Texas. As of April 2024, 41 human cases of H5 bird flu have been associated with the ongoing multi-state outbreak of A(H5N1) in dairy cattle, with 36 cases occurring in California, two cases in Michigan, and one case each reported in Colorado, Nevada and Texas. All infections occurred in dairy workers who had direct exposure to cattle presumed to be infected with A(H5N1) virus. Infections associated with U.S. dairy cattle to date have involved mild respiratory symptoms or conjunctivitis. No patients have been hospitalized.


Summary of U.S. human cases associated with poultry or backyard flock exposure

Twenty-four human cases of H5 bird flu have been detected in farm workers who were involved in the depopulation of poultry at a poultry facility experiencing an outbreak of HPAI A(H5N1) virus, and two cases involved exposures to backyard flocks in Louisiana and Wyoming. Eleven of the 24 cases in farm workers were reported in Washington state, nine in Colorado, and one each in Iowa, Ohio, Oregon, and Wyoming. Most of these workers who tested positive reported mild illness, such as redness/watery eyes and respiratory symptoms. However, one case in Ohio was severe and required hospitalization; the patient subsequently recovered. In addition, the two cases exposed to backyard birds were severe, required hospitalization, and one died.


Summary of U.S. human cases with no known animal exposure

The exposure source is unknown for three cases, two cases in children in California and one adult case in Missouri.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/pandemic-flu/php/monitoring/irat-virus-summaries.html

____

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (as of May 2 '25)



{Excerpt}

Time Period: April 20, 2025 - April 26, 2025

- H5 Detection5 sites (1.2%)

- No Detection402 sites (98.8%)

- No samples in last week91 sites




(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

____

#H5 #influenza virus #mRNA-lipid nanoparticle (LNP) #vaccination elicits adaptive immune responses in Holstein #calves

Abstract

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 is circulating widely in lactating cows in the United States. Due to the critical need for intervention strategies for this outbreak, we evaluated antibody and cellular immune responses of a clade 2.3.4.4b H5 mRNA-LNP vaccine in calves. We found that the H5 mRNA-LNP vaccine induced a robust antibody and CD8+ T cellular-mediated immune response and conferred protection against clade 2.3.4.4b H5N1 infection.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.01.651548v1

____

#Ecology and #environment predict spatially stratified #risk of #H5 highly pathogenic avian #influenza clade 2.3.4.4b in wild #birds across #Europe

Abstract

Highly pathogenic avian influenza (HPAI) represents a threat to animal and human health, with the ongoing H5N1 outbreak within the H5 2.3.4.4b clade being the largest on record. However, it remains unclear what factors have contributed to its intercontinental spread. We use Bayesian additive regression trees, a machine learning method designed for probabilistic modelling of complex nonlinear phenomena, to construct species distribution models (SDMs) for HPAI clade 2.3.4.4b presence. We identify factors driving geospatial patterns of infection and project risk distributions across Europe. Our models are time-stratified to capture both seasonal changes in risk and shifts in epidemiology associated with the succession of H5N6/H5N8 by H5N1 within the clade. While previous studies aimed to model HPAI presence from physical geography, we explicitly consider wild bird ecology by including estimates of bird species richness, abundance of specific taxa, and "abundance indices" describing total abundance of birds with high-risk behavioural traits. Our projections of HPAI clade 2.3.4.4b indicate a shift in persistent, year-round risk towards cold, low-lying regions of northwest Europe associated with H5N1. Methodologically, we demonstrate that while most variation in risk can be explained by climate and physical geography, adding host ecology is a valuable refinement to SDMs of HPAI.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.07.17.603912v2

____

Thursday, May 1, 2025

Estimation of #Incubation Period for #Oropouche Virus Disease among #Travel-Associated Cases, 2024–2025

Abstract

Determining the incubation period of Oropouche virus disease can inform clinical and public health practice. We analyzed data from 97 travel-associated cases identified by the Centers for Disease Control and Prevention (n = 74) or the GeoSentinel Network (n = 13) and 10 cases from published literature. Using log-normal interval-censored survival analysis, we estimated the median incubation period to be 3.2 (95% CI 2.5–3.9) days. Symptoms developed by 1.1 (95% CI 0.6–1.5) days for 5% of patients, 9.7 (95% CI 6.9–12.5) days for 95% of patients, and 15.4 (95% CI 9.6–21.3) days for 99% of patients. The estimated incubation period range of 1–10 days can be used to assess timing and potential source of exposure in patients with Oropouche symptoms. For patients with symptom onset >2 weeks after travel, clinicians and public health responders should consider the possibility of local vectorborne transmission or alternative modes of transmission.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/7/25-0468_article

____

The #OneHealth challenges and opportunities of the #H5N1 #outbreak in dairy #cattle in the #USA

ABSTRACT

The outbreak of H5N1 in dairy cattle in United States revealed challenges in identification and management of a novel disease. The virus showed an exceptional ability to spread between farms and among cows within a farm. The impact of the virus on dairy cattle varied from nonclinical to severe clinical signs and death. Many dairy producers did not report clinical signs in their cows or test for the virus. Cats and peridomestic birds on many affected dairies died from viral exposure. Dairy workers showed signs of conjunctivitis, which was confirmed to be due to H5N1. With the disease affecting multiple species and showing efficient cow-to-cow transmission, the situation only worsened. There was a negative impact on the relationships among dairy producers, dairy workers, poultry producers, and veterinarians, in which professional and personal relationships were severed and some experienced loss of employment. The regulatory response varied by geographic location, and in some states, animal health and human health authorities elevated producer fears of consequences of reporting. Authorities did quickly confirm that pasteurization inactivated the virus in dairy products and showed that it was very rarely detected in beef from affected cows. In this review, we will describe the relationships among the dairy industry and animal and human health and why the H5N1 outbreak requires a One Health perspective of all stakeholders in order to address it effectively.

Source: Journal of Dairy Science, https://www.journalofdairyscience.org/article/S0022-0302(25)00281-4/fulltext

____

Wednesday, April 30, 2025

#Vector competence for #Oropouche virus: A systematic #review of pre-2024 experiments

Abstract {1}

The 2023–24 epidemic of Oropouche fever in the Americas and the associated ongoing outbreak in Cuba suggests a potential state shift in the epidemiology of the disease, raising questions about which vectors are driving transmission. In this study, we conduct a systematic review of vector competence experiments with Oropouche virus (OROV, Orthobunyavirus) that were published prior to the 2023–24 epidemic season. Only seven studies were published by September 2024, highlighting the chronic neglect that Oropouche virus (like many other orthobunyaviruses) has been subjected to since its discovery in 1954. Two species of midge (Culicoides paraensis and C. sonorensis) consistently demonstrate a high competence to transmit OROV (~30%), while mosquitoes (including both Aedes and Culex spp.) exhibited an infection rate consistently below ~20%, and showed limited OROV transmission. Further research is needed to establish which vectors are involved in the ongoing outbreak in Cuba, and whether local vectors and wildlife communities create any risk of establishment in non-endemic regions.


Abstract {2}

Oropouche virus has recently become an urgent threat to public health in Central and South America. OROV is mainly transmitted by biting midges; however, some public health agencies and scientific sources note that some mosquito species transmit the virus. We conducted a systematic review of literature prior to the current epidemic, and identified seven studies that experimentally tested the ability of vectors to become infected with, and transmit OROV (i.e., that assessed their vector competence). These studies have consistently found that biting midges become infected at higher rates than mosquitoes, which rarely transmit the virus. It is unclear which vectors are responsible for transmitting OROV in the current outbreak. Existing published data support the observation that biting midges are likely to be significant vectors compared to mosquitoes, which are comparatively incompetent. However, increased vector surveillance and pathogen testing, and additional vector competence experiments using current OROV strains, are urgently needed.

Source: PLoS Neglected Tropical Diseases, https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013014

____

A #MERS-CoV-like #mink #coronavirus uses #ACE2 as entry receptor

Abstract

Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans1, the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked2. Here we report the isolation and characterization of a novel mink respiratory coronavirus (MRCoV) from farmed minks with pneumonia. Notably, MRCoV uses angiotensin-converting enzyme 2 (ACE2) as a receptor and can infect mink, bat, monkey, and human cells. Cryo-electron microscopy analysis revealed that the MRCoV receptor-binding domain (RBD) binds to the same interface on ACE2 receptors as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RBD, despite exhibiting notable structural differences. We identify the key determinants on ACE2 and MRCoV RBD that confer efficient binding. HKU5-33S, a bat coronavirus closely related to MRCoV, utilizes ACE2 of bat Pipistrellus abramus and requires only two amino acid substitutions to adapt to mink ACE2. Furthermore, SARS-CoV-2 protease and polymerase inhibitors potently block MRCoV infection, indicating a potential therapeutic strategy. Collectively, these findings enhance the understanding of coronavirus receptor dynamics and highlight their zoonotic potential. Given the risks posed by fur farms as reservoirs for emerging pathogens, our study underscores the urgent need for enhanced surveillance to mitigate future coronavirus outbreaks.

Source: Nature, https://www.nature.com/articles/s41586-025-09007-w

____

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

 Two wild servals in Dhaka Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6453

____

#SARS-CoV-2, the #human #placenta, and adverse perinatal #outcomes

Abstract

The relationship among timing and severity of COVID-19 during pregnancy, placental pathology, and adverse pregnancy outcomes is not well understood. A prospective cohort study of 497 pregnant patients with COVID-19 whose placentas underwent systematic pathologic examination was conducted. The main exposure was timing of COVID-19 during pregnancy (first/second versus third trimester). The primary outcome was composite placental pathology that included high grade maternal vascular malperfusion or greater than 25 percent perivillous fibrin deposition. There were 63 patients who had the composite placental pathology outcome. In adjusted analyses that controlled for maternal age, parity, active infection at delivery, interval from time of diagnosis to delivery and COVID-19 variant, timing of COVID-19 during pregnancy was not associated with risk of the composite placental pathology outcome. Among secondary COVID-19 related exposures that were investigated, severity of disease and treatment for COVID-19 were associated with risk of the composite placental pathology outcome. In addition, patients with COVID-19 in the first nine months of the pandemic had the highest rate of the composite placental pathology outcome. In this large cohort, placental vascular pathology was common among COVID-19 cases but was unrelated to timing of COVID-19 during pregnancy or adverse pregnancy outcomes. These findings suggest that uncomplicated COVID-19 during pregnancy does not require intensive fetal surveillance or detailed pathologic examination of the placenta after delivery.

Source: American Journal of Pathology, https://ajp.amjpathol.org/article/S0002-9440(25)00150-6/abstract?rss=yes

____

Epitope-optimized #vaccine elicits enduring #immunity against swine #influenza A virus

Abstract

Swine Influenza A Virus (IAV-S) poses a significant burden to both the pork industry and public health. Current vaccines against IAV-S are infrequently updated and induce strain-specific immunity. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines. Here, we describe the Epigraph, a computationally derived and epitope optimized set of vaccine immunogens. When compared to wildtype immunogens (WT) and a commercial comparator (FluSure XP®), pigs immunized with Epigraph demonstrate significantly improved breadth and magnitude of antibody responses. Further, pigs immunized with Epigraph show more robust and a wider breadth of cross-reactive cell-mediated immune responses than pigs immunized with WT immunogens. In an experimental infection model, Epigraph immunized pigs demonstrate a significant reduction of clinical disease, lower shedding of infectious virus, reduction of lung lesions, and lower microscopic immunopathology compared to the other immunization groups. These data support the continued investigation of computationally designed and epitope optimized vaccine immunogens against influenza A virus.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59182-7

____

Modelling a potential #zoonotic #spillover event of #H5N1 #influenza

Abstract

Highly Pathogenic Avian Influenza (HPAI) is a prominent candidate for a future human pandemic arising from a zoonotic spillover event. Its best-known strain is H5N1, with South- or South-East Asia a likely location for an initial outbreak. Such an outbreak would be initiated through a primary event of bird-to-human infection, followed by sustained human-to-human transmission. Early interventions would require the extraction, integration and interpretation of epidemiological information from the limited and noisy case data available at outbreak onset. We studied the implications of a potential zoonotic spillover of H5N1 influenza into humans. Our simulations used BharatSim, an agent-based model framework designed primarily for the population of India, but which can be tuned easily for others. We considered a synthetic population representing farm-workers (primary contacts) in a farm with infected birds. These primary contacts transfer infections to secondary (household) contacts, from where the infection spreads further. We simulate outbreak scenarios in such a setting, accounting for the network structure of human contacts and the stochasticity of the infection process. We further simulated multiple interventions, including bird-culling, quarantines, and vaccinations. We show how limited, noisy data for primary and secondary infections can be used to estimate epidemiological transmission parameters, such as the basic reproductive ratio R0, in realistic settings. We describe the impact of early interventions (bird-culling, quarantines, and vaccination), taken together or separately, in slowing or terminating the outbreak. An individual-based model allows for the most granular description of the bird-human spillover and subsequent human-to-human transmission for the case of H5N1. Such models can be contextualised to individual communities across varied geographies, given representative contact networks. We show how such models allow for the systematic real-time exploration of policy measures that could constrain disease-spread, as well as guide a better understanding of disease epidemiology.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.04.28.25326570v1

____

Diverse #Genomic #Landscape of Swine #Influenza A Virus in #England (2014 - 2021)

Abstract

Surveillance of influenza A viruses in pigs (SwIAV) is critical for identification of novel genetic groups that pose a risk to pig health and might have zoonotic potential. SwIAVs circulating in pigs in England between 2014 and 2021 were characterised using whole genome sequencing (WGS). Haemagglutinin (HA) and neuraminidase (NA) sequencing data from 82 of 368 influenza A positive samples (71 submissions) were determined, identifying H1N1 and H1N2 subtypes from the 1A classical swine and 1B human-seasonal lineages respectively. The 1B lineage viruses were predominant, accounting for 68.29% of sequenced viruses, with 1A lineage viruses comprising 31.71%, primarily from the 1A.3.3.2 clade (2009 H1N1 pandemic origin). This study characterised previously undefined diversity within the 1B lineage which led to the designation of new HA clades 1B.1.1.1, 1B.1.1.2 and 1B.1.1.3. Complete genome data were obtained from 64/82 viruses thereby updating the definition of genetic diversity thresholds and leading to the identification of 24 unique genotypes. All these 64 viruses contained PB2, PB1, PA, NP, MP, and NS gene segments of 2009 H1N1 pandemic origin. These data highlight the increasing divergence of SwIAV within pig populations England and emphasise the requirement for continued genomic surveillance to improve animal health and monitor zoonotic risk.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.28.650978v1

____

Tuesday, April 29, 2025

Early #effectiveness of #BNT162b2 #KP2 #vaccine against #COVID19 in #US VA #Healthcare System

Abstract

This test-negative case-control study within the US Veterans Affairs Healthcare System aims to estimate early vaccine effectiveness (VE) of the BNT162b2 KP.2 vaccine (2024–2025 formulation) compared to not receiving the KP.2 vaccine against COVID-19 outcomes. The study includes adult patients (age ≥18 years) with an acute respiratory infection (ARI) in hospital, emergency department and urgent care (ED/UC), or outpatient settings between September 5 and November 30, 2024. Separate multivariable logistic regression models compare the odds of receiving BNT162b2 KP.2 vaccine among SARS-CoV-2 positive cases and test-negative controls within each ARI outcome category, while adjusting for potentially confounding variables. Among 44,598 ARI episodes, VE is 68% (42–82%), 57% (46–65%), and 56% (36–69%) against COVID-19-associated hospitalizations, emergency department and urgent care visits, and outpatient visits, respectively. Uptake of updated COVID-19 vaccines is low (3.7%).

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59344-7

____

Memory T and B cells with recognition of avian #influenza #hemagglutinins are poorly responsive to existing seasonal influenza #vaccines

Abstract

Immunisation remains the most cost-effective mechanism to combat global influenza infection and is widely employed against seasonal influenza viruses. Zoonotic transmission of avian influenza A viruses represents a significant threat to human health given the lack of population level immunity, which could translate into an influenza pandemic. Therefore, there is a need to better understand pre-existing human immunity against avian influenza strains. as highlighted by the recent rapid, global spread of avian H5Nx clade 2.3.4.4b variants. Here, we sought to quantify the frequencies and specificities of B cells recognising avian hemagglutinin (HA) within unexposed adults, and to characterise the ability of seasonal immunisation to boost cross-reactive immune responses to H5Nx strains, including from clade 2.3.4.4b. Low but detectable serum antibody titres against H5 and H7 avian influenza HA were observed in donors. The frequency of memory B cells with cross-reactive recognition of H5 and H7 HA was low and 2-5 fold lower than populations of seasonal H1N1 and H3N2 HA-specific B cells. Boosting of B cell responses against H5Nx clade 2.3.4.4b HA following seasonal immunisation were sporadic with only 3 out of 19 individuals showing an increased population of probe-positive cells. Cross-reactive B cells generally expressed immunoglobulins drawn from variable heavy chain genes associated with recognition of the HA stem (VH6-1, VH1-69, VH1-18). CD4+ T cell responses towards H5 HA were also weakly boosted with little to no increase in circulating T follicular helper cell populations. These findings highlight the need for avian influenza-specific vaccine products to bolster immunity in human populations, with consideration for use in pre-pandemic preparedness to expand baseline frequencies of avian influenza-specific memory B and T lymphocytes.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.28.651131v1

____

My New Space

Most Popular Posts