#Oropouche virus infects primary #human #intestinal #organoids and is inhibited by type I and III interferon treatment

 

ABSTRACT

Oropouche virus (OROV), a neglected arbovirus, has historically been considered a self-limiting infection associated with febrile illness. However, the recent surge in cases since late 2023 has been marked by atypical outcomes, highlighting its underestimated clinical impact. Gastrointestinal symptoms such as diarrhea have also been reported, but the prevalence and mechanistic insight remain largely elusive. Here, through a meta-analysis of 12 identified clinical studies, we revealed a pooled prevalence of diarrhea as 15% (95% CI, 10%–20%) among the Oropouche patient population. In primary human intestinal organoid-based experimental models, we demonstrated productive infection by both a recent patient isolate (OROV-2024) and a historical strain (Be An19991). This is shown by the accumulation of intracellular OROV RNA, release of infectious particles, and immunostaining of OROV glycoprotein Gc. Interestingly, OROV infection mildly triggered the expression of type III interferons, but this endogenous response was insufficient to limit viral replication. In contrast, exogenous treatment with type I and III interferons strongly inhibited OROV replication, with interferon-alpha completely abolishing infectious virus production. Together, these results suggest the human intestine as a potential target organ for OROV infection and highlight interferons as potential therapeutic candidates.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/mbio.03003-25?af=R

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Genomic #Evolution of #Influenza A Virus During the 2024-2025 Season, the Johns Hopkins Health System: Antigenic Drift Reduces Serum Neutralization

 

Abstract

Introduction

Seasonal influenza causes significant global morbidity, mortality, and economic burden. Ongoing viral evolution can lead to vaccine mismatch and the emergence of antiviral resistance, highlighting the importance of genomic surveillance. The 2024–2025 influenza season was characterized by high incidence and increased hospitalizations.

Methods

We analyzed influenza A virus (IAV) genomes and clinical characteristics from the 2024–2025 season. Whole-genome sequencing was performed on 648 influenza A–positive clinical specimens collected between October 2024 and April 2025.

Results

Hemagglutinin (HA) sequences were recovered from 74.23% (481/648) of samples and used for subtyping and phylogenetic analysis. A(H1N1)pdm09 and A(H3N2) viruses co-circulated, representing 55.5% and 44.5% of cases, respectively. Among A(H1N1)pdm09 viruses, the HA1 substitution T120A, located near the Sa antigenic site, increased more than twofold compared with the prior season. Circulating A(H3N2) viruses belonged to multiple HA subclades and exhibited distinct amino acid substitutions at key antigenic sites. Neutralization assays using sera from individuals vaccinated with the 2024–2025 seasonal influenza vaccine demonstrated reduced neutralization of three dominant A(H1N1)pdm09 isolates and two A(H3N2) isolates compared with vaccine strains, consistent with antigenic drift. In addition, the neuraminidase substitution S247N, previously associated with reduced oseltamivir susceptibility, was detected in 13.9% of A(H1N1)pdm09 samples.

Discussion

These findings demonstrate ongoing antigenic drift and the presence of antiviral resistance–associated mutations during the 2024–2025 influenza season, underscoring the need for continued genomic surveillance to guide vaccine and antiviral strategies.

Source: 

Link: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiag069/8461561#google_vignette

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Post-exposure #prophylaxis with #favipiravir among #household close contacts to confirmed #COVID19 cases: A cluster-randomized trial (PEPfavi)

 

Abstract

Background

Household transmission of SARS-CoV-2 remains a key driver of community spread, with secondary attack rates in Thai households reaching approximately 50 %. There is limited evidence supporting the efficacy of antiviral post-exposure prophylaxis (PEP) in this context.

Methods

The phase 2/3, open-label, (1:1) cluster-randomized controlled trial in Thailand, 168 household close contacts from 76 index cases were enrolled to receive either favipiravir-PEP (FPV-PEP) (1600–2000 mg/day for 7 days) or usual care. The efficacy of FPV-PEP was investigated in preventing SARS-CoV-2 infection after contact with index cases.

Results

The incidence of confirmed SARS-CoV-2 infection was lower in the FPV-PEP group than in the usual care group (7.32 % vs. 14.47 %), although the difference was not statistically significant. A trend toward fewer early positive rapid diagnostic test results on day 3 was observed in the FPV-PEP group. Symptom development was less frequent among FPV-PEP recipients, with fewer cases of fever, rhinorrhea, and myalgia. A significantly higher probability of remaining asymptomatic and delayed symptom onset was observed in the FPV-PEP group. No participants developed severe COVID-19 or required hospitalization.

Conclusion

FPV-PEP was associated with a lower incidence of fever, rhinorrhea, and myalgia among household contacts. While a reduction in secondary transmission was observed, it did not reach statistical significance. Further large-scale studies are warranted to clarify its role in preventing household transmission.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1876034126000225?via%3Dihub

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Protective Efficacy of a #Hemagglutinin-Based #mRNA #Vaccine Against #H5N1 #Influenza Virus Challenge in Lactating Dairy #Cows

 

Abstract

Highly pathogenic avian influenza H5N1 virus has spread to over 1,080 dairy farms across 18 states in the United States, resulting in 41 human infections and posing serious risks to both animal and public health. To address these risks, a hemagglutinin-based mRNA–lipid nanoparticle vaccine was developed, and its safety, immunogenicity, and protective efficacy in high-yielding lactating dairy cows were evaluated. The vaccine was well tolerated, had no adverse effects on health or milk production, and induced strong antibody responses. Two weeks after the second immunization, all the immunized cattle were fully protected against a high-dose H5N1 virus challenge. Notably, two-thirds of the cattle were still completely protected even at the 19th week after the first vaccination, when their serum antibody levels were very low. These data demonstrate that the mRNA vaccine confers robust, lasting protection against H5N1 virus in lactating dairy cows, providing a foundation for clinical trials.

Source: 

Link: https://spj.science.org/doi/10.34133/research.1104

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#Antigenic #Drift and Antivaccine Shift in the 2025–2026 #Influenza Season

 

{Summary}

Recent headlines about influenza have reported a “super flu” causing a “record-breaking season” that is “overwhelming hospitals.” Although less dramatic, data from the Centers for Disease Control and Prevention (CDC) reveal substantial influenza activity: the agency estimated that there were more than 20 million cases of influenza illness, 270,000 influenza-related hospitalizations, and 11,000 deaths from influenza in the United States through January 24, 2026. These numbers aren’t extraordinary as compared with those from previous seasons, but some indicators of influenza activity and severity have been remarkable.

(...)

Source: 

Link: https://www.nejm.org/doi/full/10.1056/NEJMp2600395?query=TOC

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The #impact of clade B #lineage 5 #MERS #coronaviruses #spike #mutations from 2015 to 2023 on virus entry and replication competence

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus that can cause zoonotic disease in humans with lethal severe viral pneumonia. Dromedary camels are the source of zoonotic infection. As of November 2025, MERS-CoV has resulted in a total of 2630 reported cases, 37% of these being fatal. The number of reported human cases has been on a decreasing trend since 2016 and reached a nadir during the COVID-19 pandemic. The reason for the reduction of cases is unclear and may be multifactorial. We hypothesized that mutations accumulating in the virus spike protein may have reduced zoonotic potential. Here, we investigate the impact of recently emerged virus spike-protein mutations on virus replication competence using pseudoviruses and replication-competent recombinant viruses. We found that virus spike variants detected in 2019 and some from 2023 show a reduced cell entry, lower viral replication and reduced fitness in human primary alveolar epithelial cells and multiple cell lines. All the MERS-CoV spikes tested showed a cell-entry pathway preference via the cell-surface TMPRSS2 route. Mechanistically, we showed the V530A mutation in the 2019 spike sequence had a reduced human DPP4 binding phenotype. Our data highlighted MERS-CoV spike mutations can modulate viral fitness in human cells and provide new insights to understand recent MERS epidemiology.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013336

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Rapid #Risk #Assessment - #MERS-CoV, Eastern Mediterranean Region (#WHO, Feb. 3 '26, summary)

 

Risk statement  

-- The scope of this Rapid Risk Assessment is to reassess the epidemiological situation of Middle East respiratory syndrome coronavirus (MERS-CoV) following the recent exportation (in December 2025) of cases from the Arabian Peninsula to France and three healthcare-associated clusters reported by the Kingdom of Saudi Arabia (KSA) in 2024–2025. 

-- These events, together with the continued occurrence of sporadic cases in Arabian Peninsula countries, highlight the ongoing risk of international spread to non-endemic countries and reflect the persistent circulation of MERS-CoV in the Middle East.  

-- Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus transmitted to humans through direct or indirect contact with infected dromedary camels, which are the natural host of the virus. 

-- First identified in humans in 2012 in the Kingdom of Saudi Arabia (KSA) and Jordan, MERS-CoV causes a viral respiratory infection that occurs throughout the year, with cases reported sporadically and in clusters. 

-- Clinical presentation ranges from asymptomatic or mild respiratory illness to severe acute respiratory disease, pneumonia, and death. 

-- The case fatality rate among cases reported to WHO is 37%.    

-- Since MERS-CoV emergence in 2012, until 23 January 2026, under the International Health Regulations (IHR, 2005), 27 countries have reported human cases of MERS-CoV to the WHO: 

- Algeria, 

- Austria, 

- Bahrain, 

- China, 

- Egypt, 

- France, 

- Germany, 

- Greece, 

- the Islamic Republic of Iran, 

- Italy, 

- Jordan, 

- Kuwait, 

- Lebanon, 

- Malaysia, 

- the Netherlands, 

- Oman, 

- the Philippines, 

- Qatar, 

- the Republic of Korea, 

- the Kingdom of Saudi Arabia (KSA), 

- Thailand, 

- Tunisia, 

- Türkiye, 

- the United Arab Emirates (UAE), 

- the United Kingdom, 

- the United States of America, and 

- Yemen.    

-- However, of the 2635 MERS cases documented globally since 2012, 2418 (92%) were reported from the WHO Eastern Mediterranean Region (EMR). 

-- The majority (84%) of reported cases were notified by KSA (2224/2635) followed by other Arabian Peninsula countries: the UAE (94), Jordan (28), Qatar (28), Oman (26), Iran (6), Kuwait (4), Tunisia (3), Lebanon (2), Bahrain (1), Egypt (1) and Yemen (1).  

-- Exposure was commonly linked to direct or indirect contact with infected dromedary camels or transmission from infected individuals in healthcare settings or households. 

-- Most cases reported outside the Arabian Peninsula countries involved people likely infected there prior to travelling elsewhere.    

-- Following the first human infection with MERS-CoV in 2012, the Director‐General convened an Emergency Committee under the International Health Regulations (IHR 2005) in 2013 to assess whether the outbreaks of MERS constituted a Public Health Emergency of International Concern (PHEIC) and to provide guidance on the public health measures that should be taken.{i}  

-- The Committee has met on 10 occasions and, on each occasion, concluded that the outbreaks do not meet the criteria of a PHEIC.    

-- The overall risk of MERS-CoV in 2023 was assessed as moderate both at the regional and global levels.  

-- A new assessment currently confirms that this risk level remains unchanged, moderate both at the regional and global levels, taking into account the following considerations:  

- 1. Continued reports of sporadic cases in endemic countries in the Arabian Peninsula and the occasional occurrence of traveller cases and healthcare-associated transmission, including two cases reported from France in December 2025 and three clusters reported in the Kingdom of Saudi Arabia during 2024–2025. 

- 2. Since the last RRA in 2023, cases reported to WHO have not resulted in sustained onward human-tohuman transmission, as most identified close contacts tested negative and no additional household clusters have been identified. The three healthcare-related clusters remained limited, with infection only confirmed in direct contacts with the index case. 

- 3. The observed decline in reported MERS cases since 2020, in particular during the COVID-19 pandemic emergency phase, is thought to be a result of pandemic-related Infection Prevention & Control measures that also limited human-to-human transmission of MERS-CoV, as well as behavioural changes during the pandemic. Any role of potential cross-reactive immunity from SARS-CoV-2 infection and/ or vaccination remains in need of further investigation. Other hypotheses—such as reduced surveillance, viral attenuation, or decreased circulation in camel populations—are not supported by current evidence. 

- 4. Significant disparities persist globally in countries' capacities to detect and respond effectively to the disease, particularly in regions where the virus has not been previously documented. Within the EMR, six fragile, conflict-affected, and vulnerable countries are considered at greater risk.  

- 5. Global inequalities remain in the adequacy of preparedness, infection prevention and control capacities, and response measures, particularly in the context of a cross-border outbreak or a traveller case.  

- 6. MERS-CoV continues to circulate in dromedary camel populations without causing overt clinical signs, constituting a constant source of human exposure and a risk of zoonotic spillover, which may result in occasional onward human-to-human transmission. The recent detection of Clade B viruses in camels of African origin further highlights the risk of MERS-CoV spread from the Arabian Peninsula via camel movements and poses an additional risk to other regions, particularly given the documented increased replication competence and more efficient viral entry of Clade B compared with Clade C. 

- 7. Preliminary data from in vitro growth kinetics and partial sequencing indicate no major attenuation in circulating Clade B strains. 

- 8. The potential public health impact of MERS-CoV should not be underestimated given the severity of disease and its high reported case fatality rate (CFR), even though sustained global spread is currently considered unlikely.  

- 9. MERS-CoV can cause severe disease resulting in high mortality. The current CFR of 37% is based on laboratory-confirmed cases only and may therefore overestimate of the true mortality rate.  

- 10. Existing regional and global surveillance systems may fail to detect asymptomatic and mild cases of MERS, leading to underreporting.  

- 11. Limited and non-sustained human-to-human transmission has been documented, mainly in healthcare and household settings. However, due to limited research, data gaps remain in understanding transmission dynamics, including the role of environmental contaminations, asymptomatic cases and specific exposure risk in healthcare settings. Further research is needed to better understand zoonotic transmission associated with dromedary camel products and excreta.  

- 12. Due to the similarity of symptoms with other respiratory diseases that are widely circulating, like influenza or COVID-19, detection and diagnosis of MERS cases may be delayed, especially in unaffected countries, creating opportunity for local onward transmission.  

- 13. Should MERS-CoV result in a healthcare-associated outbreak in a previously unaffected country, as occurred in the Republic of Korea in May 2015, during which 186 laboratory-confirmed cases (185 in the Republic of Korea and 1 in China) and 38 deaths were reported, the public health consequences for that country could be substantial.  

- 14. The recent exportation of cases from the Arabian Peninsula to France demonstrates the ongoing risk of international spread. 

(...)

__

{1} Confidence refers to the level of confidence in the data/information or the quality of the evidence available at the time the RRA is conducted. Poor quality information may increase the overall perceived risk due to the incertitude in the assessment 

___

Source: 

Link: https://www.who.int/publications/m/item/who-rapid-risk-assessment-mers-cov--eastern-mediterranean-region-v.2

____

Long Term Rapid #Risk #Assessment, Acute Event of Potential Public Health Concern: #COVID19, Global (#WHO, Feb. 3 '26, summary)

 

{Summary}

Overall risk statement

-- At the end of 2025, the global public health risk from COVID-19 remained moderate, following the declining deaths and hospitalizations in 2022 due to high population immunity, improved clinical management, and similar virulence and characterized by sustained stability in severity indicators—including ICU admissions and in hospital mortality—throughout the following years. 

-- Most SARS-CoV-2 variants now belong to the JN.1 Omicron sublineages, which show immune escape but do not result in increased disease severity compared to other Omicron sublineages. 

-- Nonetheless, continued surveillance gaps, reduced genomic sequencing and sharing of sequence information, and limited reporting, especially from low- and middle-income countries, undermine a more informed risk assessment at this time. 

-- SARS-CoV-2 continues to circulate widely, as indicated by sentinel surveillance under GISRS and wastewater surveillance, co-circulating with seasonal influenza and Respiratory Syncytial Virus (RSV). 

-- Post COVID-19 condition is estimated to affect around 6% of symptomatic cases, with reduced risk in vaccinated individuals. 

-- WHO has developed the Strategic Plan for Coronavirus Disease Threat Management (2025–2030) which continues to encourage integration of COVID19 into broader respiratory disease surveillance systems and recommend vaccination of populations at high-risk of severe disease. 

-- While available vaccines remain effective against severe disease and death despite continued variant evolution, global vaccine uptake among high-risk groups was very low in 2025. 

-- Overall, while the direct impact of COVID-19 has lessened since 2022, ongoing circulation and virus evolution in human populations and established animal reservoirs, low vaccine uptake, and insufficient burden and genomic surveillance data contribute to continued uncertainty, requiring constant vigilance. 

(...)

Mortality 

-- As of 28 December 2025, over seven million confirmed deaths had been reported globally to WHO. 

-- The number of weekly reported COVID-19-related deaths has been steadily declining, now consistently below 2000 since February 2024. 

-- This is a significant decrease compared to previous periods, such as the 6 000 average deaths reported per week in 2023 and the over 24 000 in 2022. 

-- Similar to case reporting, the weekly average number of countries (including areas and territories) reporting at least one death has declined from 222 in 2022 to 157 and 74 in the same periods of 2023 and 2024, respectively.   

-- In 2025 (as of 28 December), 26 424 deaths were reported from 46 countries, averaging 510 deaths across 38 countries per week. 

-- Since the beginning of 2024, global reporting of COVID-19 deaths has been predominantly driven by countries in the Region of the Americas and the European Region. 

-- It is important to note that absence of official reporting to WHO does not imply that COVID-19 related deaths are not occurring in non-reporting countries. 

-- The overall decline in reported deaths coincides with a reduction in the number of countries reporting, limiting the interpretation of global trends due to decreased geographic and income level representativeness. 

-- As a result, it is difficult to determine with certainty whether the observed decline reflects a true decrease at global level. 

-- However, data from mainly high-income countries that have maintained consistent surveillance and reporting indicate a continued downward trend in deaths, likely reflecting increased population-level immunity due to infections and vaccination. 

-- As an indicator of severity, data collected from countries reporting both hospitalizations and deaths showed a decreasing trend in number of deaths per 1000 hospitalizations in February 2021, when it was 246 deaths per 1000 hospitalizations, to under 100 deaths per 1000 hospitalizations as of the end of July 2022. 

-- Since mid-2022, this indicator has remained generally stable, with fluctuations between 30 to 100 deaths per 1000 hospitalizations. 

-- While the causes for these changes cannot be directly interpreted from data available due to their non-representative nature, they are likely due to a combination of increases in infection- and/or vaccinederived immunity, improvements in early diagnosis and clinical care, reduced strain on health systems, change in the surveillance systems and other factors. 

-- It is not possible to infer a decreased or increased intrinsic virulence of newer SARS-CoV-2 variants from these data.  

-- Nevertheless, the reported figures are an underestimate of the true death toll, which has been estimated by several groups, including WHO. (35) 

-- It is worth highlighting that most countries do not differentiate COVID-19 deaths and hospitalizations between those directly caused by SARS-CoV-2 and those testing positive for the virus incidentally. 

-- The population aged 65 years and over, and those who are not vaccinated, continue to be most at risk of severe disease and death. 

-- In 2025, 37 countries from the African Region, the Region of the Americas, the European Region and the Western Pacific Region reported deaths with age information which represents a decrease from 42 countries across the Region of the Americas, European Region and Western Pacific Region in 2024. 

-- Information on age was available for 25 039 deaths, representing 95% of the total 26 424 reported deaths in 2025. 

-- The population 65 years and over constituted 88% of all deaths during 2025. 

-- While similar to the figure reported in 2024, it nevertheless represents the highest proportion of deaths attributed to a single age group since the beginning of the pandemic. 

-- Those aged 15 to 64 years constituted 11.7% of all deaths, presenting a slight increase from 11.3% compared to 2024. 

-- These data were consistently provided by the Region of the Americas and the European Region. 

-- When compared, the proportion of deaths among those aged 15 to 64 were higher in the Region of the Americas (13%) than the European Region (5.8%). 

-- In 2025, less than 1% (n=187) of reported deaths occurred among children under 15 years of age – a consistent trend since the emergence of SARS-CoV-2.

-- However, a more detailed look reveals that 154 out of 187 (82%) deaths occurred in children under five years old, indicating that this age group remains the most vulnerable compared to older children. 

(...)

Source: 

Link: https://www.who.int/publications/m/item/covid-19-global-risk-assessment--version-9

____

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

 

A wild Mute Swan in Žilinský Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7246

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Advancing #H5N1 #influenza #risk #assessment in #ferrets through comparative evaluation of airborne virus shedding patterns

 

Abstract

Recent A(H5N1) zoonotic cases linked to poultry and cattle in North America highlight the urgent need to assess the pandemic potential of emerging strains. Using male ferrets, we evaluate two B3.13 and two D1.1 genotype A(H5N1) viruses isolated from humans and observe fatal disease and varying capacities for direct contact transmission. To enhance pandemic risk assessment, we conduct aerosol sampling using cyclone BC251 and water condensation capture-based SPOT samplers and perform comparative analyses to include additional A(H5N1), A(H9N2), A(H7N9), and A(H1N1)pdm09 strains with known transmissibility profiles. Although none of the A(H5N1) strains transmit via the air, B3.13 viruses are detected at significantly higher levels compared to D1.1 strains. Here we show strong correlations between viral loads in nasal washes, airborne virus shedding, and transmissibility in ferrets, highlighting the value of these metrics for identifying zoonotic influenza viruses that may be adapting toward increased transmission potential.

Source: 

Link: https://www.nature.com/articles/s41467-026-68931-1

____

#Potential and #challenges for sustainable #progress in human #longevity

 

Abstract

Decelerating gains in life expectancy (e0) in high-income countries have raised concerns about the future of human longevity. To enhance our understanding of these developments, we examine subnational (N = 450) mortality trends in Western Europe in the period 1992-2019. Between 1992 and 2005, gains in life expectancy were both substantial and widespread. Laggard regions experienced the fastest improvements, yielding rapid regional convergence. Between 2005 and 2019, however, gains in these regions decelerated, while remaining remarkably stable in vanguard regions, suggesting that it remains possible to continue extending longevity. The observed slowing of e0 gains is strongly associated with mortality at ages 55-74, which increased in this period across large areas of Western Europe, particularly in Germany and France. In this work, we show that monitoring mortality trends at a fine geographical level is crucial for revealing both the potential for, and challenges to, sustainable progress in human longevity.

Source: 

Link: https://www.nature.com/articles/s41467-026-68828-z

____

Crowning with Thorns, Titian (c.1570 - c.1575)

 

Public Domain

Source: 

Link: https://www.wikiart.org/en/titian/crowning-with-thorns

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An intranasal adenoviral-vectored #vaccine protects against highly pathogenic avian #influenza #H5N1 in naive and antigen-experienced #animals

 

Highlights

• IN-delivered ChAd-Texas vaccine elicits mucosal antibody and T cell responses

• IN-delivered ChAd-Texas vaccine protects against H5N1 in mice and hamsters

• IN delivery of ChAd-Texas vaccine confers greater protection than IM delivery

• ChAd-Texas induces H5N1 immunity in the setting of prior influenza immunity

Summary

The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic. To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents. Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell responses and confers greater protection than intramuscular immunization. In Syrian hamsters, a single intranasal dose of ChAd-Texas vaccine prevents weight loss and reduces airway infection after H5N1 A/Michigan/90/2024 or A/Texas/37/2024 challenge. Importantly, prior seasonal influenza vaccination does not impair antibody responses or protection after intranasal delivery of the ChAd-Texas vaccine. These results support the development of mucosally administered ChAd-Texas HA vaccines as an effective platform for HPAI H5N1 preparedness.

Source: 

Link: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00655-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS266637912500655X%3Fshowall%3Dtrue

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Dual roles for #influenza A protein #PAX: limiting inflammatory response and disrupting #MHC I #antigen presentation in #human respiratory epithelium

Abstract

Key to the success of influenza A virus as a pathogen are its numerous tactics of immune evasion. To suppress anti-viral cellular and organismal responses, influenza A virus encodes several immunomodulatory proteins, including the endoribonuclease PA-X. PA-X decreases inflammation and immune responses in in vivo infections by limiting host gene expression. PA-X is conserved in 99% of all influenza A viral strains, pointing to its importance as a crucial immunomodulator. However, it is not yet known how PA-X activity alters the antiviral response in the human airway or how it benefits the virus. To define how influenza A virus uses this protein to evade immune responses, we characterized the impacts of PA-X on the host response to infection in the infected and bystander cells of the airway epithelium using a 3D ex vivo model. We discovered that PA-X exerts a dual action on immune responses, dampening aspects of both the innate and adaptive immune systems. Consistent with reports in model organisms, PA-X significantly decreases secretion of multiple cytokines from airway epithelium, including IFN-λ, which likely plays a role in its ability to reduce inflammation and lung damage. In addition, we revealed that PA-X decreases and delays MHC I antigen presentation from infected cells. This reduction likely aids influenza A virus in hiding from antigen-specific T cells and allows the virus to successfully replicate prior to immune detection. This new function for PA-X highlights how influenza A virus employs active mechanisms to block immune detection, in addition to tolerating high levels of antigen mutations to escape it. Moreover, as evasion of recognition by the adaptive immune system is particularly important during infections of animals and humans with pre-existing immunity, this immunomodulatory activity may be key to the longevity of influenza A viruses and their continued circulation.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, https://ror.org/043z4tv69, R01AI137358, 75N93021C00017

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.30.702929v1

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History of Mass Transportation: A 44-ton 1-B-1 experimental gas-turbine locomotive designed by R. Tom Sawyer and built in 1952 for testing by the U.S. Army Transportation Corps

 By Kbh3rd - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5545061

Source: 

Link: https://en.wikipedia.org/wiki/Gas-turbine_locomotive

____

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    Radiology

11. SPOSATO A, Mazzola MA, Kunst MM
    Case 346.
    Radiology. 2026;318:e251975.
    PubMed         Abstract available
    
    

    
    Travel Med Infect Dis

12. HUANG SH, Lin YC, Shih YL, Kuo JS, et al
    Impact of the COVID-19 Pandemic on Travel Medicine Services in Taiwan, 2019-2022.
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    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Jan. 31 '26)

 

Am J Med

1. CHENG Y, Ling Y, Scholten J, Atkins D, et al
   Patterns and trends in prevalent central nervous system stimulant use in US veterans with traumatic brain injury.
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   PubMed         Abstract available
   
   

   
   BMC Pediatr

2. AKAR A
   Rare disease mimicking multisystem inflammatory syndrome in children.
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   PubMed         Abstract available
   
   

   
   Cell

3. PEKAR JE, Crespo-Bellido A, Lemey P, Bowman AS, et al
   Can H5N1 avian influenza in dairy cattle be contained in the US?
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   PubMed         Abstract available
   
   

   
   J Clin Microbiol

4. XU X, Hull W, Plunkett D, Tu ZJ, et al
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   J Infect Dis

5. ZHONG JC, Zhong S, Touyon L, Ho F, et al
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7. DAULAGALA P, Cowling BJ, Yen HL
   Response to Letter to the Editor regarding the immunogenicity of enhanced influenza vaccines in inducing neuraminidase inhibition antibodies.
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   Lancet

8. WHITAKER M, Elliott J, Gerard-Ursin I, Cooke GS, et al
   Profiling vaccine attitudes and subsequent uptake in 1.1 million people in England: a nationwide cohort study.
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   PLoS Comput Biol

9. TRIPATHY SS, Puthussery JV, Kapoor TS, Cirrito JR, et al
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   PLoS One

10. XU M, Shi J, Wang Y, Wu J, et al
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    Virology

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Genetic diversity of alpha and #betacoronaviruses in cave and temple-roosting #bats in #Vientiane Province, #Lao PDR

 

Abstract

The emergence of MERS-CoV, SARS-CoV-1, and SARS-CoV-2 highlights the significant public health and economic threats posed by coronaviruses. In Lao PDR, SARS-CoV-2-related bat coronaviruses capable of binding to human ACE2 receptors have been found in northern regions, but little is known about coronavirus diversity in anthropized environments like temples. This study investigated coronavirus circulation, diversity, and prevalence in bats from caves and temples in Vientiane Province, Lao PDR. A total of 648 guano samples (505 Chaerephon plicatus, 100 Hipposideros spp., 43 Taphozous spp.) were collected between December 2022 and June 2023 and screened using pan-coronavirus RT-PCR approach. The overall positivity rate was 17.28%, significantly higher in caves (18.8%) than temples (4.41%) (p = 0.003). C. plicatus showed the highest positivity rate (21.38%), followed by Hipposideros spp. 4%, while Taphozous spp. were negative. Phylogenetic analysis revealed diverse coronavirus lineages within Alphacoronavirus (80.4%) and Betacoronavirus (19.6%) genera. Although none were closely related to known human pathogens, coronaviruses of Decacovirus genus related to Chinese bat viruses and Pedacovirus genus similar to porcine epidemic diarrhea virus (PEDV) were detected. Unclassified betacoronaviruses identified were also related to viruses from C. plicatus in Thailand. This study provides valuable insights into coronavirus circulation in both natural and anthropized environments. The detection of PEDV-like viruses underlines the need for continued surveillance at the human-bat interface, where activities like guano harvesting and temple visits increase contacts. Further genomic and functional studies would enhance our understanding of their evolutionary relationships and potential for further cross-species transmission.

Source: 

Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0341737

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History of Mass Transportation: The Davenport 1597 Steam Locomotive preserved by Illawarra Light Railway Museum

 

By Hpeterswald - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=28169917

Source: 

Link: https://en.wikipedia.org/wiki/Davenport_Locomotive_Works

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Retail #Milk #Monitoring of #Influenza #H5N1 in Dairy #Cattle, #USA, 2024–2025

 

Abstract

US retail milk monitoring during April 13–May 3, 2024, identified influenza A(H5N1) viral RNA in 36% of retail milk samples, indicating widespread undetected infections in US dairy cows. After federal initiatives, reported infections more closely aligned with findings in retail milk during December 27, 2024–January 29, 2025, reflecting improved detection and control.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/2/25-1332_article

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