Pathogens最新文献

{"title":"Pilot Assessment of RNA Stabilization Methods for Influenza A Virus in Swine Oral Fluids.","authors":"Berenice Munguía-Ramírez, Betsy Armenta-Leyva, Luis Giménez-Lirola, Yanqi Zhang, Bailey Arruda, Giovana Ciacci-Zanella, Jeffrey Zimmerman","doi":"10.3390/pathogens15040439","DOIUrl":"10.3390/pathogens15040439","url":null,"abstract":"<p><p>Influenza A virus (IAV) surveillance in swine relies heavily on molecular detection, yet RNA stability in diagnostic specimens such as oral fluids can be rapidly compromised when cold-chain conditions are not maintained. This pilot study evaluated the ability of four molecular-grade carbohydrates (20% trehalose, sorbitol, sucrose, and mannitol) and two commercial nucleic acid stabilizers (PrimeStore^® MTM and RNA<i>later</i>^®) to preserve RT-qPCR-detectable IAV RNA in swine oral fluids exposed to field-relevant stress conditions. Oral fluid samples collected from pigs experimentally infected with H1N2 (Study 1: <i>n</i> = 150; DPIs 2, 3, 4) or with H1N2 and H3N2 (Study 2: <i>n</i> = 58; DPI 5) were subjected to storage at 25 °C for up to 144 h (Study 1) or 2, 5, 10, or 15 freeze-thaw cycles (Study 2), with DPIs (Study 1) or subtypes (Study 2) serving as biological replicates, given the limited sample size. IAV detection was quantified as efficiency standardized Cq values (ECq) and analyzed using a linear mixed-effects model. Overall, both carbohydrates (trehalose, sorbitol, sucrose) and commercial stabilizers maintained higher ECq values than untreated oral fluids under both thermal and freeze-thaw stress conditions. Due to the limited sample size, these findings should be interpreted cautiously, yet they demonstrate the potential utility of carbohydrates as a low-cost, non-inactivating alternative for stabilizing IAV RNA in field-collected oral fluids.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecological Frameworks of Pathogen-Pathogen and Pathogen-Microbiome Interactions Within the Tick Holobiont.","authors":"Elianne Piloto-Sardiñas, Islay Rodríguez, Huarrisson Azevedo Santos, Patrícia Gonzaga Paulino, Belkis Corona-González, Alejandro Cabezas-Cruz","doi":"10.3390/pathogens15040440","DOIUrl":"10.3390/pathogens15040440","url":null,"abstract":"<p><p>Ticks harbor complex microbial communities composed of symbionts, commensals, and tick-borne pathogens (TBPs). Together, these microorganisms form the tick holobiont. Within this system, the tick's physiological architecture structures microbial communities by distributing microorganisms across distinct tissues. This compartmentalization creates spatially distinct ecological niches, which in turn shape how microbial communities assemble and interact. In this review, we integrate ecological theory with current knowledge of tick microbiome research to examine how pathogen-pathogen and pathogen-microbiome interactions emerge within these tissue-structured microbial communities. We first outline how baseline ecological filters, including tick species, developmental stage, tissue identity, vertical transmission, and environmental context, shape the microbiome configuration through community assembly processes. We then examined how TBPs, as high-impact colonizers, can further modify microbial networks by altering host-mediated selective pressures, influencing interaction topology, and reshaping community stability. Based on these observations, we propose a dual selective pressure framework in which (i) baseline ecological structuring processes and (ii) pathogen-associated selective pressures interact to determine the microbial network configuration and functional outcomes within the tick holobiont. These interacting forces may drive shifts in diversity, modularity, keystone taxa emergence, and network resilience, ultimately influencing vector competence. This review frames the microbial communities within the tick holobiont as spatially structured ecological systems shaped by multilevel selective pressures. This conceptual foundation provides a coherent framework for understanding microbial interactions in arthropod vectors and highlights avenues for mechanistic research and microbiome-based strategies to mitigate tick-borne diseases.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-β Modulates Early Viral Replication Kinetics and Innate Responses to Non-Fatal Alphavirus Encephalomyelitis.","authors":"Benjamin H Nguyen, Elise Stanley, Victoria K Baxter, Diane E Griffin","doi":"10.3390/pathogens15040441","DOIUrl":"10.3390/pathogens15040441","url":null,"abstract":"<p><p>Alphaviruses are mosquito-borne viruses that can infect the central nervous system (CNS) and cause encephalomyelitis, which is a rare but dangerous complication from infection. In mice, this can be studied in a model of infection with Sindbis virus (SINV), which infects neurons and causes neurological disease. Due to the non-renewable nature of neurons, the immune response in the CNS is specialized to prevent neuronal damage or death, even if they are infected. Therefore, insights into the nuances of antiviral immunity in the CNS provide a better understanding of disease pathogenesis and mechanisms of recovery. Type I interferons (IFNs) are critically important for survival; they are an innate antiviral defense mechanism that consists mainly of IFNα and IFNβ. Although both use the same receptor, type-specific differences between IFNα and IFNβ have been described in other contexts. To this end, <i>Ifnb</i>^-/- mice were used to elucidate the role of IFNβ in recovery from alphavirus encephalomyelitis. IFNβ-deficient mice have intact IFNα expression and downstream signaling, but symptomatic disease occurs earlier and is more severe. This is accompanied by increased virus replication in the early stages of infection. Microgliosis is reduced in <i>Ifnb</i>^-/- mice compared to wildtype, but inflammatory cytokine/chemokine levels are higher and associated with alterations in monocyte and NK cell recruitment into the CNS. <i>Ifnb</i>^-/- mice have no deficiencies in the expression of factors known to be required for viral clearance. Therefore, IFNβ modulates the early stages of the immune response and facilitates restriction of virus replication, contributing to delayed disease onset.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Diversity and Virulence Potential of High-Priority Critically Important Antimicrobial-Resistant <i>Escherichia coli</i> from Pork and Chicken Retail Meat.","authors":"Hernán D Nievas, Camila Aurnague, Elisa Helman, Raúl E Iza, Magdalena Costa, Oliver Mounsey, Matthew B Avison, Lucía Galli, Fabiana A Moredo","doi":"10.3390/pathogens15040438","DOIUrl":"10.3390/pathogens15040438","url":null,"abstract":"<p><p>The occurrence of <i>Escherichia coli</i> resistant to high-priority critically important antimicrobials (HPCIA) in the food chain is a growing concern for food safety and public health. This study aimed to evaluate whether HPCIA-resistant <i>E. coli</i> isolated from pork and chicken meat at retail markets in La Plata, Buenos Aires, Argentina, exhibit source-associated genomic differentiation through whole-genome sequencing. The isolates displayed a polyclonal population structure, encompassing multiple phylogenetic groups and sequence types. Virulence gene profiles were highly diverse, with chicken-derived isolates harbouring a substantially higher number of virulence genes than pork isolates. Notably, one pork isolate carried a complete set of virulence genes characteristic of diarrheagenic <i>E. coli</i>. Single Nucleotide Polymorphism-based phylogenetic analysis revealed several closely related subclusters, including strains recovered from both pork and chicken meat from the same retail markets, suggesting recent clonal sharing or cross-contamination at the point of sale. These findings highlight the circulation of genetically diverse HPCIA-resistant <i>E. coli</i> in retail meat, underscoring the potential public health risk and the importance of monitoring resistance and virulence determinants throughout the food production chain.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Murine Disseminated Candidiasis, Serum Amyloid P Component Inhibits Inflammation and C-Reactive Protein Potentiates Inflammation.","authors":"Stephen A Klotz, Richard E Sobonya, Peter N Lipke","doi":"10.3390/pathogens15040436","DOIUrl":"10.3390/pathogens15040436","url":null,"abstract":"<p><p><i>Candida albicans</i> is a ubiquitous commensal fungus that may be lethal once it gains access to the bloodstream, following a breach in protective barriers such as skin or gut lining. Intravenous injection of <i>C. albicans</i> (4.5 × 10⁴ yeasts/gm of mouse) leads reproducibly to systemic infection with a median survival of about 75 h. We studied the effects of two human innate immune effectors on the course of systemic infections. The soluble human pentraxin serum amyloid P component (hSAP) retards death in murine disseminated candidiasis. In contrast, another soluble pentraxin, human C-reactive protein (hCRP), hastens death. To examine the pathological basis for these differences, necropsies were performed, and the right kidney was removed for study. Candidiasis caused abundant collagen deposition (the precursor to fibrosis) and loss of contrast between the kidney medulla and cortex. Daily administration of subcutaneous hSAP following the intravenous injection of <i>C. albicans</i> preserved the discrete histological difference between cortex and medulla and lessened host collagen deposition. Yeasts and hyphae within abscesses were decorated with hSAP. Contrastingly, kidneys from animals administered <i>C. albicans</i> and hCRP showed extensive collagen deposition and loss of the boundary between the cortex and the medulla of the kidney. hCRP did not bind to fungi but bound to damaged tissue surrounding abscesses, leading to a more destructive infection with loss of tissue. Staining cells with antibodies to CD45 (to detect T-lymphocytes, myelocytes, monocytes, and macrophages) and antibodies to Ly-6G (neutrophils, and granulocytes) showed that hSAP retarded infiltration of inflammatory cells into diseased areas. The results are consistent with the hypothesis that early administration of hSAP represses the migration of inflammatory cells, dampens the production of collagen by fibroblasts, and dampens the overall immune response of the host to infection. In doing so, hSAP prolonged life, whereas hCRP facilitated the infectious process and hastened death.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imported Pediatric Lyme Disease in Singapore-A Case Series.","authors":"Ade Xin Ning Tan, Ilyas Hussin, Chia Yin Chong, Matthias Maiwald, Terri Xiao-Bei Chiong, Natalie Woon Hui Tan","doi":"10.3390/pathogens15040437","DOIUrl":"10.3390/pathogens15040437","url":null,"abstract":"<p><p>Lyme disease is the most common reported vector-borne disease in North America and is also highly prevalent across Europe. Although tick-borne diseases are uncommon in Singapore, there remains a risk of imported tick-borne diseases among travelers from endemic regions. We present a case series of three pediatric patients with imported Lyme disease managed at a tertiary children's hospital in Singapore, illustrating the varied clinical presentations of Lyme disease in children. One child developed meningitis following prior antibiotic therapy for Lyme disease, although causality cannot be definitively established. This series aims to highlight key diagnostic considerations and management principles relevant to clinicians practicing in non-endemic regions.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of IL-6 and IL-8 Levels and Other Bio Markers in Predicting Dengue Severity Across Serotypes.","authors":"Kumar Sivasubramanian, Rudrappan Raj Bharath, Leela Kakithakara Vajravelu, Madan Kumar D, Jayakrishna Pamarthi","doi":"10.3390/pathogens15040434","DOIUrl":"10.3390/pathogens15040434","url":null,"abstract":"<p><strong>Background: </strong>Dengue fever is one of the most common mosquito-borne viral infections, with severe cases characterized by plasma leakage, hemorrhage, and multi-organ involvement. Identification of dengue serotypes and reliable biomarkers is essential for predicting disease progression and guiding timely interventions.</p><p><strong>Methods: </strong>This prospective cohort study was conducted at a super-speciality tertiary care hospital in southern India from July 2024 to July 2025. A total of 69 patients presenting with dengue warning signs were included in the study. Patients were categorized into the severe dengue group (<i>n</i> = 25) and non severe dengue group (<i>n</i> = 44). Clinical data, laboratory findings, dengue serotype, and serial serum samples collected on Days 1, 4, and 8 were analyzed to evaluate the predictive and monitoring efficacy of Interleukin-6 (IL-6) and Interleukin-8 (IL-8), and followed up till discharge.</p><p><strong>Results: </strong>Out of 69 dengue patients with warning signs, 32 dengue-positive patients were serotyped, which included DEN V-1 (31.3%), DEN V-2 (31.3%), DEN V-3 (15.6%), DEN V-4 (18.8%), and mixed DEN V-(2 + 3) (3.1%). Severe dengue patients exhibited a higher frequency of secondary dengue infection (IgG) than primary dengue infection (88% vs. 12%), with statistically significantly higher packed cell volume, hemoglobin levels, high AST levels, and prolonged activated partial thromboplastin time, as well as lower platelet counts and albumin levels. Platelet transfusion was given to 35 dengue patients, which had also resulted in significant length of stay in hospital in comparison to non-transfused patients. IL-6 and IL-8 levels were significantly elevated in severe dengue patients when compared to non-severe dengue patients on Day 1 and Day 4, followed by a decline on Day 8, corresponding with clinical recovery. However, the elevated IL-8 levels were observed to be significantly associated with longer hospital stays, indicating its potential role as an early predictor of disease progression.</p><p><strong>Conclusions: </strong>The observed co-circulation of multiple serotypes reflects the hyper-endemic pattern reported across India. Early measurement of these cytokines IL-6 and IL-8 helps distinguish severe from non-severe dengue among patients presenting with warning signs. IL-6 and IL-8 may have potential as biomarkers for disease severity. However their role in guiding platelet transfusion requires further investigation in non-severe cases and prioritizing timely management for those at higher risk of severe disease.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Characterization and Preliminary NGS Profiling of Terbinafine-Resistant <i>Trichophyton indotineae</i> Isolates in Italy.","authors":"Deborah Cruciani, Manuela Papini, Luigi Pisano, Roberta Calcaterra, Donatella Pietrella, Tommaso Galeotti, Paolo Fazii, Antonia Meloscia, Martina Torricelli, Marco Di Domenico, Alessandro Fiorucci, Sara Spina, Silvia Crotti","doi":"10.3390/pathogens15040435","DOIUrl":"10.3390/pathogens15040435","url":null,"abstract":"<p><p><i>Trichophyton indotineae</i> is an emerging dermatophyte associated with extensive, chronic, recalcitrant, and frequently terbinafine-resistant dermatophytosis worldwide. In this study, 30 <i>T. indotineae</i> strains isolated in Italy were investigated. The isolates were obtained from patients originating from Asian countries, from patients from other countries, and from Italian patients who reported no travel outside Italy in the preceding years. Clinical isolates were identified by internal transcribed spacer (ITS) sequencing and analyzed to assess the occurrence and molecular basis of terbinafine resistance. Terbinafine resistance was detected in 18 strains (60%) using a real-time PCR assay. Sequencing of the squalene epoxidase (<i>SQLE</i>) gene revealed mutations associated with resistance, including L393S in nine strains and F397L in another nine strains. NGS analysis confirmed two terbinafine-resistant strains carrying the L393S and F397L mutations, respectively, and detected the A448T mutation in one terbinafine-susceptible strain. These findings demonstrate the presence of terbinafine-resistant <i>T. indotineae</i> across five regions of Italy and confirm the occurrence of <i>SQLE</i> mutations previously linked to antifungal resistance. Data obtained also support a link with endemic Asian areas, other than suggesting the possible occurrence of autochthonous transmission in Italy.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional and Biochemical Characterization of Spermidine Synthase CauSpe3 from <i>Candidozyma auris</i>.","authors":"Jae-Yeon Choi, Pallavi Singh, Choukri Ben Mamoun","doi":"10.3390/pathogens15040432","DOIUrl":"10.3390/pathogens15040432","url":null,"abstract":"<p><p>Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl group from decarboxylated S-adenosylmethionine (dc-SAM) to putrescine to form spermidine. Although genomic analyses predict the presence of SPDS homologs in multiple fungal species, polyamine biosynthesis has not been experimentally characterized in the multidrug-resistant fungal pathogen <i>Candidozyma auris</i>. Here, we report the biochemical and functional characterization of the <i>C. auris</i> spermidine synthase, CauSpe3. The <i>CauSPE3</i> gene complemented a <i>Saccharomyces cerevisiae spe3Δ</i> mutant demonstrating conserved function <i>in vivo</i>. Recombinant CauSpe3 was expressed in <i>Escherichia coli</i>, purified and analyzed using the fluorescence-based DAB-APT assay, which uses 1,2-diacetylbenzene (DAB) for polyamine detection. CauSpe3 catalyzed efficient conversion of putrescine to spermidine in the presence of dc-SAM, with <i>K_half</i> values of 65.5 ± 7.11 µM for putrescine and 66.9 ± 2.09 µM for dc-SAM, and <i>V_max</i> values of 7.1 ± 0.57 and 7.9 ± 0.12 nmol·µg^-1·min^-1, respectively. A catalytic-site mutant and heat-inactivated enzyme showed no detectable activity, and product formation was confirmed by means of thin-layer chromatography and mass spectrometry. These findings establish CauSpe3 as a functional spermidine synthase.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13118584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Vitamin D3 Supplementation on 28-Day ICU Mortality in Sepsis Patients: A Retrospective Study with Propensity Score Matching.","authors":"Xiaofei Huang, Anqiang Zhang, Dalin Wen, He Li, Ling Zeng","doi":"10.3390/pathogens15040433","DOIUrl":"10.3390/pathogens15040433","url":null,"abstract":"<p><p>Reduced levels of vitamin D are associated with increased incidence and mortality of sepsis. Nonetheless, the effectiveness of vitamin D supplementation in improving sepsis patients' outcomes continues to be debated. In this research, which was conducted as a retrospective cohort analysis, data obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV 3.0) were used. The focus of the study was on vitamin D3 administration to sepsis patients while in the ICU. The primary outcome measurement was 28-day ICU mortality, with secondary outcomes of mechanical ventilation duration, percentage of patients receiving mechanical ventilation, and ICU stay length. The Kaplan-Meier curve analysis, Cox regression analysis, and subgroup analyses were performed to explore the link between vitamin D3 supplementation and sepsis prognosis. A 1:1 propensity score matching (PSM) approach was used to strengthen the reliability of the results. Before matching, the cohort comprised 28,524 patients, which was reduced to 4,856 after PSM. The analysis revealed that vitamin D3 supplementation was associated with a lower 28-day ICU mortality rate (HR = 0.71, 95% CI: 0.64-0.78, <i>p</i> < 0.001). Kaplan-Meier curve analysis revealed significantly greater survival probabilities in the group receiving vitamin D3 than in the group not receiving vitamin D3 (<i>p</i> < 0.001). Subgroup analysis showed that total cumulative exposure to vitamin D3 was more strongly associated with 28-day ICU mortality (<i>p</i> < 0.001), whereas daily dose and dosing frequency showed no significant association. The results after PSM and subgroup analysis were consistent with those of the original cohort study, further confirming the robustness of the results. Overall, vitamin D3 supplementation is associated with lower 28-day ICU mortality and better outcomes in patients with sepsis. However, given the retrospective observational design, large-scale prospective randomized controlled trials are warranted to validate these observational associations and establish causal effects.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}