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#Azelastine Nasal #Spray for #Prevention of #SARS-CoV-2 Infections A Phase 2 #RCT

  Key Points -- Question:  Is regular application of azelastine nasal spray associated with reduced risk of SARS-CoV-2 infections? - Findings:  In this randomized placebo-controlled clinical trial that included 450 participants , the incidence of laboratory-confirmed SARS-CoV-2 infections was significantly lower with application of azelastine nasal spray compared with placebo treatment. -- Meaning:  The use of azelastine nasal spray may help to reduce the risk of SARS-CoV-2 infections. Abstract Importance    Limited pharmaceutical options exist for preexposure prophylaxis of COVID-19 beyond vaccination. Azelastine, an antihistamine nasal spray used for decades to treat allergic rhinitis, has in vitro antiviral activity against respiratory viruses, including SARS-CoV-2. Objective    To determine the efficacy and safety of azelastine nasal spray for prevention of SARS-CoV-2 infections in healthy adults. Design, Setting, and Participants   ...

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

  {A Great White Pelican, one of the affected species in the outbreak.} 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=66151818 Wild birds of different species in Western Cape Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6732 ____

#Placental transfer of #medications to treat #COVID19, #molnupiravir, #favipiravir and #nirmatrelvir/ritonavir, in the ex vivo human cotyledon model

  Abstract Objectives There have been few studies in pregnant women of medications that are used to reduce severe complications from COVID-19 infection. Currently, nirmatrelvir/ritonavir (Paxlovid) is recommended by the National Institutes for Health to treat non-hospitalized pregnant patients with mild-to-moderate COVID-19 illness. The aim of this study was to determine the transplacental passage of molnupiravir, nirmatrelvir/ritonavir and favipiravir utilizing an ex vivo placental perfusion model. Methods Human placental cotyledons were continuously perfused in a double open circuit. The study molecules and antipyrine, a marker of placental viability, were dissolved in the maternal solution. The experiment was conducted over 90 minutes, and every 5 minutes, samples of the maternal solution and fetal exchange solutions were collected for analysis. We calculated the concentrations of study molecules, fetal transfer ratios and the clearance indexes to determine placental transfer. R...

The #cow udder is a potential mixing vessel for #influenza A viruses

  Abstract The incursion of high pathogenicity avian influenza A virus (IAV) into US dairy cows is unprecedented in the era of molecular diagnosis and pathogen sequencing. This raises questions over the likelihood of further outbreaks and whether dairy cattle could be a mixing vessel for novel strains of IAV. Using a panel of BSL2-safe reassortant viruses representing clade 2.3.4.4b H5 epizootic lineages circulating since 2020, we found that a cow B3.13 isolate displayed enhanced replication in cow mammary gland cells , along with increased viral polymerase activity and stronger interferon antagonism in cow cells compared to an earlier EA-2020-C genotype virus. However, multiple avian and mammalian IAV strains , including other clade 2.3.4.4b high pathogenicity genotypes, were replication competent in bovine cells, particularly those of the mammary gland , suggesting that there is a diverse circulating IAV pool with the potential to infect cows. Moreover, we show that cow mammary c...

The Bridge at Narni, Camille Corot (1826)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/camille-corot/the-augustan-bridge-at-narni-1826 ____

#Vectors on the Move: How #Climate Change Fuels the Spread of #Arboviruses in #Europe

  Abstract Climate change is increasingly recognized as a major driver of emerging infectious diseases, particularly vector-borne diseases (VBDs), which are expanding in range and intensity worldwide. Europe , traditionally considered low-risk for many arboviral infections , is now experiencing autochthonous transmission of pathogens such as dengue, chikungunya, Zika virus, West Nile virus, malaria, and leishmaniasis . Rising temperatures , altered precipitation patterns , and milder winters have facilitated the establishment and spread of competent vectors , including Aedes, Anopheles, Phlebotomus, and Culex species , in previously non-endemic areas. These climatic shifts not only impact vector survival and distribution but also influence vector competence and pathogen development , ultimately increasing transmission potential. This narrative review explores the complex relationship between climate change and VBDs, with a particular focus on pediatric populations . It highlights h...

Ciliated cells promote high infectious potential of #influenza A virus through the efficient intracellular activation of #hemagglutinin

  ABSTRACT Influenza viruses utilize host proteases to activate the viral fusion protein, hemagglutinin (HA), into its fusion-competent form. Although proteolytic activation of HA is essential for virus replication, the cell-type dependence of HA activation within the airway epithelium and the subcellular location(s) in which it occurs are not well established. To address these questions, we investigated the proteolytic activation of HA in differentiated human airway epithelial cells using contemporary and historical H1N1 and H3N2 strains . We find that activation is efficient across viral strains and subtypes but depends on cellular tropism , with ciliated cells activating HA more effectively than non-ciliated cells. Similar to prior observations in immortalized cell lines, we find that HA activation occurs intracellularly, constraining the antiviral activity of host-directed protease inhibitors . These results establish that HA activation within the airway epithelium depends on c...

Evolving #Threats: Adaptive Mechanisms of #Monkeypox Virus (MPXV) in the 2022 Global #Outbreak and Their Implications for #Vaccine Strategies

  Abstract Monkeypox virus (MPXV) experienced an unprecedented global outbreak in 2022, characterized by a significant departure from historical patterns: a rapid spread of the epidemic to more than 110 non-traditional endemic countries , with more than 90,000 confirmed cases; a fundamental shift in the mode of transmission , with human-to-human transmission (especially among men who have sex with men (MSM)) becoming the dominant route (95.2%); and genetic sequencing revealing a key adaptive mutation in a novel evolutionary branch ( Clade IIb ) that triggered the outbreak. These features highlight the significant evolution of MPXV in terms of host adaptation, transmission efficiency, and immune escape ability . The aim of this paper is to provide insights into the viral adaptive evolutionary mechanisms driving this global outbreak, with a particular focus on the role of immune escape (e.g., novel mechanisms of M2 proteins targeting the T cell co-stimulatory pathway) in enhancing vi...

Stabilization of the trimeric pre-fusion structures of #influenza #H1 and #H9 #hemagglutinins by mutations in the stem helices

  Abstract Stabilizing the pre-fusion structures of antigenic proteins can enhance the effectiveness of antiviral vaccines . The pre-fusion form of hemagglutinin (HA) from the influenza virus typically adopts a stable trimeric structure . However, the recombinant ectodomain of HA from the A/California/04/2009 (H1N1) influenza virus formed a monomer in solution rather than the expected trimer. To promote trimer formation in the pre-fusion conformation, we redesigned five amino acid residues in the stem region of HA that are involved in trimerization. The engineered HA protein formed a stable trimer at both pH 8.0 and pH 5.5. Additionally, the thermal stability of the modified protein improved, as indicated by an approximately ten-degree increase in its denaturation temperature. Cryo-EM analysis at 2.2 angstrom resolution confirmed that the mutant HA protein adopted the pre-fusion structure. Furthermore, the stabilized mutant exhibited enhanced immunogenicity in mice . We applied the...

History of Mass Transportation: The SNCF X 4500 Autorail

  By Florian PĂ©pellin - Own work, CC BY-SA 3.0,  https://commons.wikimedia.org/w/index.php?curid=36916592 Source: Wikipedia,  https://en.wikipedia.org/wiki/SNCF_Class_X_4500 ____

#Coronavirus Disease Research #References (by AMEDEO, August 30 '25)

  Br J Anaesth STEPHENS JR, Iki Y, Yasuda T, Brown E, et al Human neutrophil-derived extracellular vesicles induce renal endothelial inflammation in critical illness: an ex vivo investigation. Br J Anaesth. 2025 Aug 27:S0007-0912(25)00448-9. doi: 10.1016/j.bja.2025. PubMed           Abstract available Clin Infect Dis YONG MK, Thursky K, Crane M, Spelman T, et al Interferon-alpha Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Infect Dis. 2025 Aug 28:ciaf409. doi: 10.1093. PubMed           Abstract available Emerg Infect Dis DRATCH AH, Le M, Zahn M Increased Incidence of Candida auris Colonization in Early COVID-19 Pandemic, Orange County, California, USA. Emerg Infect Dis. 2025;31:1747-1754. PubMed           Abstract available J Med Virol CHAUVEL C, Casalegno JS, Visseaux B, Vieillefond V, e...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, August 30 '25)

  Arch Virol HU Y, Hu C, Su J, Zhu B, et al Two cross-neutralizing antibodies isolated from a COVID-19 convalescent via single B cell sorting. Arch Virol. 2025;170:199. PubMed           Abstract available Biochemistry ADEWOYE A, Ezeigbo E, Vo QH, Legleiter J, et al Amyloidogenic SARS-CoV-2 Spike Protein-Derived Peptides Form Oligomers and Selectively Damage Lipid Membranes. Biochemistry. 2025;64:3610-3622. PubMed           Abstract available Epidemiol Infect PARRADO R, Cuba-Grandy CX, Fuentes-Luppichini E, Torrico Villarroel NG, et al Multiplex RT-qPCR strategy for SARS-CoV-2 variants detection in developing countries without ngs: The Bolivian experience. Epidemiol Infect. 2025;153:e94. PubMed           Abstract available BUBAR K, Middleton C, Larremore D, Gostic K, et al A fundamental limit to the effectiveness of traveller screening with molecular tests. Epidemi...

The Trans-Kingdom #Spectrum of #Mpox-like Lesion Pustules of Suspect #Patients in the Mpox Clade Ib #Outbreak in Eastern #DRC

  Abstract During infectious disease outbreaks, acquiring genetic data across various kingdoms offers essential information to tailor precise treatment methodologies and bolster clinical, epidemiological, and public health awareness. Metagenomics sequencing has paved the way for personalized treatment approaches and streamlined the monitoring process for both co-infections and opportunistic infections. In this study, we conducted long-read metagenomic DNA sequencing on mpox-like lesion pustules from six suspected patients who were positive and confirmed to be infected with MPXV during the MPXV subclade Ib outbreak in the Eastern Democratic Republic of the Congo. The sequenced data were taxonomically classified as bacterial, fungal, and viral in composition . Our results show a wide spectrum of microorganisms present in the lesions . Bacteria such as Corynebacterium amycolatum, Gardnerella vaginalis, Enterococcus faecium, Enterobacter clocae, Staphylococcus epidermidis, and Stenotro...

#Cholera – Multi-country with a focus on countries experiencing current surges (#WHO D.O.N., August 29 '25)

  {Summary} Situation at a glance The global cholera situation continues to deteriorate , driven by conflict and poverty, posing a significant public health challenge across multiple WHO regions.  Between 1 January and 17 August 2025, a total of 409 222 cholera/Acute Watery Diarrhoea (AWD) cases and 4738 deaths were reported globally, from 31 countries , with six of the 31 countries reporting case fatality rates above 1%, indicating serious gaps in case management and delayed access to care.  Cholera is resurging in a number of countries , including some that had not reported substantial case numbers in years, like Chad and the Republic of Congo , while other countries, such as the Democratic Republic of the Congo , South Sudan , and Sudan , are experiencing outbreaks that are continuing from 2024, with significant geographic expansion. This complicates containment efforts and strains fragile health systems.  Conflict, mass displacement, disasters from natural hazard...

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 subtype 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 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 primary contacts in an outbreak site with infected birds. These primary contacts transfer infections to secondary ( household) cont...

#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, August 29 '25)

  {Summary} Time Period: August 17, 2025 - August 23, 2025 -- H5 Detection :  2 sites ( 0.5% ) -- No Detection :  429 sites ( 99.5% ) -- No samples in last week :  31 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

#Pathogenicity of #SARS-CoV-2 #Omicron #Subvariants #JN.1, #KP.2, and #EG.5.1 in K18-hACE2 Transgenic #Mice

  Abstract The emergence of the SARS-CoV-2 JN.1 lineage in late 2023 marked a major shift in viral evolution . By January 2024, it had displaced XBB variants to become the dominant strain worldwide. JN.1 and its descendants are antigenically distinct from earlier Omicron subvariants , with approximately 30 additional spike mutations compared to XBB-derived viruses. The combination of these features alongside growing evidence of considerable immune evasion prompted the FDA to recommend that vaccine formulations be updated to target JN.1 rather than XBB.1.5. The continued dominance of JN.1-derived variants necessitates the characterization of viral infection in established animal models to inform vaccine efficacy and elucidate host–pathogen interactions driving disease outcomes. In this study, transgenic mice expressing human ACE2 were infected with SARS-CoV-2 subvariants JN.1, KP.2, and EG.5.1 to compare the pathogenicity of JN.1-lineage and XBB-lineage SARS-CoV-2 viruses. Infection...

#Mpox Multi-country external #situation #report no. 57 published 28 August 2025 (#WHO, summary)

  Highlights     • All clades of monkeypox virus (MPXV) continue to circulate in several countries.  - When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, they continue to pose a risk of sustained community transmission .  - Since the last edition of this report , one country, Senegal , has reported mpox for the first time . Efforts to identify the clade are underway.  • Furthermore, TĂ¼rkiye has reported cases of mpox due to clade Ib MPXV for the first time and the Democratic Republic of Congo has reported its first cases of mpox due to clade IIb MPXV.   • In July 2025, 47 countries in five (out of six) WHO regions reported a total of 3924 confirmed cases , including 30 deaths (case fatality ratio [CFR] 0.8% ).  - The South-East Asian and Western Pacific regions reported an increase in cases in July 2025, while the African Region, European Region and the Region of the Americas reported a decrease....

#Italy, Integrated #WNV & #USUV #Surveillance - Weekly #Bulletin No. 7 - 28 August 2025 (summary)

  {Summary} -- During surveillance week from 21 to 27 August , 79 new confirmed human cases of West Nile Virus infection have been reported.  -- Since the beginning of the epidemic season, the total number of confirmed cases have risen to  430 (they were  351 in the last bulletin); of these: -  193 were West Nile Neuroinvasive Disease cases: 8 in Piedmont, 12 Lombardy, 14 Veneto, 1 Friuli-Venezia Giulia, 1 Liguria, 13 Emilia-Romagna, 62 Latium, 2 Molise, 64 Campania, 2 Basilicata, 5 Calabria, 1 Sicily, 8 Sardinia),  - 38 were asymptomatic cases among blood donors ,  - 193 were West Nile Fever cases,  - 3 asymptomatic and  - 3 unspecified cases.  -- Among the confirmed cases, there were 27 fatalities : 1 Piedmont, 1 Lombardy, 1 Emilia-Romagna, 11 Latium, 11 Campania, 2 Calabria).  - The Case-Fatality Rate in WNND cases is so far at 13.9% (during 2018 it was 20%, in 2024 14%).  -- One confirmed human case of Usutu virus infectio...