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TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.4 weeks agoHuman TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds 9 and 10 showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound 9 displayed a synergistic effect with baloxavir during IAV H1N1 infection. Both compounds highly reduced H1N1 infection in air-liquid interface cultures and mouse models, thus highlighting their broad antiviral potential. The discovery of broad-spectrum, host-directed antivirals against current and emerging human viruses is critical in preparing for future pandemics.Chronic respiratory diseaseCare/Management
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Localized Outbreak of Macrolide-Resistant Pertussis in Infants, Japan, March-May 2025.4 weeks agoA localized pertussis outbreak involving 10 unvaccinated infants occurred in Kumamoto, Japan, during March-May 2025. Nine infants were admitted to the pediatric intensive care unit, 6 of whom received a confirmed diagnosis of macrolide-resistant Bordetella pertussis infection. This outbreak highlights the importance of booster vaccinations and resistance surveillance.Chronic respiratory diseaseCare/ManagementAdvocacy
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Molecular Analysis of Emerging MT27 Macrolide-Resistant Bordetella pertussis, Kobe, Japan, 2025.4 weeks agoWe report the emergence and spread of multilocus variable-number tandem-repeat analysis type 27 (MT-27) macrolide-resistant Bordetella pertussis (MRBP) in Kobe, Japan, in 2025. Whole-genome sequencing revealed that MT27-MRBP did not originate from the widely circulating MT27 macrolide-sensitive B. pertussis in Japan but was closely related to MRBP in China.Chronic respiratory diseaseCare/Management
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Effect of Chloramine Disinfection of Community Water System on Legionnaires' Disease Outbreak, Minnesota, USA, 2024.4 weeks agoThe Minnesota Department of Health identified an outbreak of Legionnaires' disease in a city in northern Minnesota, USA, in April 2023 that continued until chloramine disinfection of the community water system was implemented. Before chloramine disinfection was implemented, Legionella pneumophila was detected in 1 of 16 samples from the drinking water distribution system and in 5 of 10 premise plumbing samples using both cultivation-dependent (Legiolert) and cultivation-independent (digital PCR) assays in this independent investigation. Approximately 11 weeks after disinfection was implemented, all distribution system samples tested negative; however, 1 of 6 Legiolert-tested and 3 of 6 digital PCR-tested premise plumbing samples were positive. After 24 weeks of disinfection, all samples collected from the distribution system and premise plumbing tested negative. Our results show that a community water system supplied by groundwater supported substantial growth of L. pneumophila in premise plumbing and that chloramine disinfection halted the outbreak.Chronic respiratory diseaseCare/ManagementAdvocacy
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Enhanced Isolation and Detection of COVID-19 in Hospitalized Patients Undergoing Antiviral Therapy.4 weeks agoWe evaluated the efficiency of SARS-CoV-2 detection from patient respiratory specimens by comparing 3 cell lines: Vero E6, Vero E6 expressing transmembrane protease serine 2 (Vero E6 T2), and Vero E6 expressing angiotensin-converting enzyme 2 and transmembrane protease serine 2 (Vero E6 A2T2). We compared a range of sample types, clinical conditions, and real-time reverse transcription PCR cycle threshold values. Vero E6 A2T2 exhibited enhanced sensitivity by supporting efficient virus entry and replication with faster cytopathic effect. Vero E6 culture isolated infectious virus only up to 3 days after PCR confirmation but with Vero E6 A2T2 cells, culture occurred up to 7 days after confirmation. Whole-genome sequencing showed no evidence of adaptive mutations when Vero E6 A2T2 was used for viral culture, supporting use for downstream analyses. Optimized infectious virus detection systems are needed for research and clinical settings, particularly for high-risk, immunocompromised populations that produce virus longer and contribute to variant emergence.Chronic respiratory diseaseCare/Management
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Clinical Manifestations of Emerging Trichosporon spp. Infections, France.4 weeks agoFungi in the family Trichosporonaceae are rarely involved in invasive disease but are frequently associated with colonization or respiratory allergic infection. Trichosporonaceae exhibit intrinsic resistance to echinocandin antimicrobial drugs, posing challenges for treatment and contributing to high mortality rates. We complied a nationwide analysis of 112 cases of invasive disease caused by Trichosporon spp. and related fungi, diagnosed in France over 20 years, that combined clinical data, susceptibility profiles, and molecular identification. We identified 12 species; T. asahii was the most common species recovered, and the new species T. austroamericanum was next. Comparison of clinical data highlighted species and genotypic differences, such as a much higher proportion of children infected by T. asahii and major differences in antimicrobial drug susceptibility. Correct identification is not only of epidemiologic interest but also necessary for patient management because of the varying clinical and microbiological characteristics found in different species.Chronic respiratory diseaseCare/Management
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Detection of Novel Thermotolerant Tepidimonas sp. Bacteria in Human Respiratory Specimens, Hong Kong, China, 2024.4 weeks agoIn patients with acute respiratory infections (ARIs), routine diagnostic tests often fail to identify the microbial cause; thus, many ARIs have undetermined etiology. We investigated potential involvement of thermotolerant bacteria in ARIs among patients in Hong Kong, China, by incubating blood agar inoculated with respiratory specimens at 50°C for 5 days. Among 7,257 specimens analyzed, 58 specimens from 57 patients grew thermotolerant bacteria not identified by other methods. We identified Tepidimonas spp. in 42 isolates, 3 of which appear to be a novel Tepidimonas species (tentatively Tepidimonas hongkongensis sp. nov). Genomic analysis revealed various virulence, resistance, and stress-related genomes in the 3 isolates. Tepidimonas spp. bacteria were predominantly isolated from patients with chronic lung disease and malignancies. We also detected T. hongkongensis in hospital water samples but at a lower percentage than in respiratory specimens, suggesting colonization potential. Clinical implications of T. hongkongensis remain unknown; continued surveillance could determine its role in ARIs.Chronic respiratory diseaseCare/Management
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Integration of bioinformatic tools for the detection of SARS-CoV-2 co-infection cases.4 weeks agoCo-infection with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, though rare, may have clinical and public health implications, including facilitating variant recombination. Early detection of co-infections is, therefore, crucial. In this study, we report two probable cases of co-infection identified during routine genomic surveillance. Initially suspected as cross-contamination due to the presence of private mutations and nucleotide mixtures flagged by Nextclade and bammix, the samples were re-extracted and re-sequenced after workspace decontamination, yet the anomalies persisted. To investigate further, we developed a bioinformatics pipeline (Katmon) incorporating various tools such as Freyja, with lineage abundance results that illustrated the presence of multiple variants, and VirStrain, which confirmed inconsistent lineage assignments. We also visualized the alternative allele fractions for each lineage-defining mutation and amplicon, showing evidence of two variants, Delta and Omicron, co-existing within a single amplicon. Amplicon sorting effectively separated reads corresponding to the two variants, and the resulting consensus sequences aligned with their respective lineage assignments. These findings suggest that the first sample, PH-RITM-1395, involved a Delta-Omicron co-infection, while the second sample, PH-RITM-4146, probably contains both a co-infection and a recombinant variant. To further support the second sample's recombinant nature, we employed sc2rf, which identified Delta-Omicron breakpoints. Retrospective analysis of 1,078 samples from July 2021 to July 2022, encompassing the period of co-circulation of different variants in the Philippines, flagged four additional co-infection cases, including Delta-Omicron and Beta-Omicron, suggesting a lower bound co-infection prevalence of 0.27% and 0.19%, respectively. Furthermore, the pipeline was used to test previously identified co-infections of different variants from different countries. Our findings underscore the critical importance of real-time genomic surveillance and advanced bioinformatics pipelines in detecting SARS-CoV-2 co-infections and variant recombination.Chronic respiratory diseaseCare/Management
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Does land cover affect the growth rate of COVID-19? Rethinking sustainable habitat from the One Health perspective using data from 12 cities during lockdown in Hubei Province, China.4 weeks agoThe COVID-19 pandemic has drawn attention to the interconnected roles of environmental conditions and public health beyond conventional medical explanations. The One Health (OH) perspective offers a collaborative and interdisciplinary perspective that integrates humans, animals, plants, and their shared environment to achieve optimal health outcomes. The 12 cities in Hubei Province that experienced lockdown during the peak phase of COVID-19 (February 1 to March 4, 2020) provided unique samples. In this study, land cover was selected as the environmental variable, and the COVID-19 growth rate was used as the infectious disease indicator to examine their relationship, thereby investigating the potential role of environmental factors in epidemic control.
The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the most influential variables for subsequent analyses. Spatial autocorrelation was assessed using Moran's I in RStudio, while spatial dependence was explicitly modeled through the Spatial Autoregressive (SAR) and Spatial Lag of X (SLX) models to evaluate the effects of explanatory variables while accounting for spatial interactions. All results were interpreted within the One Health perspective, considering the source of infection, routes of transmission, and susceptible populations.
LASSO regression identified wetland, cultivated land, orchard land, forest land, and population density as the main factors associated with the COVID-19 growth rate. Wetland coverage exhibited a significant positive association with growth rate, whereas cultivated land showed a negative but marginally significant relationship. Orchard land and forest land were associated with weak negative effects.
The statistical results indicate that variations in land cover influence the growth rate of COVID-19 cases, suggesting that environmental management, including wetland and wastewater control, agricultural landscape configuration, forest vegetation preservation, and control population density, may help mitigate infectious disease growth. From the One Health perspective, sustainable habitat design and planning strategies and land use policies were proposed for future research.Chronic respiratory diseaseAdvocacy -
Public-private partnerships are critical for rapid response to infectious disease threats.4 weeks agoPublic-private partnerships focused on infectious disease diagnostics have been increasing since the COVID-19 pandemic. These partnerships have resulted in new test development, increased testing capacity and services, technology development, and processes to enable faster collaborative response in the context of an outbreak. This paper explores the importance of public-private partnerships in response to infectious disease public health threats. Collaboration between federal partners and diagnostic test manufacturers has been critical to the COVID-19, mpox, and other responses in the United States, and these partnerships will be critical to future responses. Public-private partnerships pull together the pieces needed to rapidly develop and scale diagnostics necessary for responding to emerging infectious diseases. Developing partnerships during "peace time" further enables rapid action when outbreaks occur.Chronic respiratory diseaseAdvocacy