Pub Date : 2026-01-01Epub Date: 2025-12-05DOI: 10.1016/j.jinf.2025.106664
Molin Yue , Sojin Lee , Shiyue Tao , Geizecler Tomazetto , Kristin Yahner , Hui Liu , Matthew C. Lee , Mary Patricia Nowalk , Richard K. Zimmerman , Monika Johnson , William MacDonald , Erick Forno , Wei Chen , Nader Shaikh
Prediction of outcomes of SARS-CoV-2 infection remains challenging, particularly in the early days following exposure. To better understand the heterogeneity of disease progression, we investigated the early immune response in the upper respiratory tract using transcriptomic analysis, comparing individuals who remained asymptomatic to those who developed symptoms of COVID-19. We conducted a study of 74 individuals (43 children, 31 adults) with confirmed SARS-CoV-2 infection. Mid-turbinate nasal swabs were collected during the first few days of infection and again one week later. We performed a paired analysis comparing baseline and follow-up nasal human gene expression. Additionally, we conducted a predictive analysis to identify transcripts associated with the development of symptomatic infection. From the differentially expressed transcripts in both analyses, we developed a predictive model to assess the likelihood of symptomatic disease. We also compared gene expression patterns between children and adults. A robust interferon response in the upper respiratory tract was strongly associated with the development of symptomatic infection. A panel of five interferon-stimulated genes (TAP2, DDX60, IFIT5, APOL6, and IFI6) predicted symptomatic infection with reasonable accuracy (area under the curve = 0.84). Notably, adaptive immune responses, including T-cell activation and cytokine signaling, differed substantially between children and adults. Our findings suggest that early measurement of interferon-stimulated gene expression may help identify individuals at risk of developing symptomatic COVID-19.
{"title":"Upper airway transcriptomics early after SARS-CoV-2 infection to identify individuals likely to develop symptomatic infection","authors":"Molin Yue , Sojin Lee , Shiyue Tao , Geizecler Tomazetto , Kristin Yahner , Hui Liu , Matthew C. Lee , Mary Patricia Nowalk , Richard K. Zimmerman , Monika Johnson , William MacDonald , Erick Forno , Wei Chen , Nader Shaikh","doi":"10.1016/j.jinf.2025.106664","DOIUrl":"10.1016/j.jinf.2025.106664","url":null,"abstract":"<div><div>Prediction of outcomes of SARS-CoV-2 infection remains challenging, particularly in the early days following exposure. To better understand the heterogeneity of disease progression, we investigated the early immune response in the upper respiratory tract using transcriptomic analysis, comparing individuals who remained asymptomatic to those who developed symptoms of COVID-19. We conducted a study of 74 individuals (43 children, 31 adults) with confirmed SARS-CoV-2 infection. Mid-turbinate nasal swabs were collected during the first few days of infection and again one week later. We performed a paired analysis comparing baseline and follow-up nasal human gene expression. Additionally, we conducted a predictive analysis to identify transcripts associated with the development of symptomatic infection. From the differentially expressed transcripts in both analyses, we developed a predictive model to assess the likelihood of symptomatic disease. We also compared gene expression patterns between children and adults. A robust interferon response in the upper respiratory tract was strongly associated with the development of symptomatic infection. A panel of five interferon-stimulated genes (<em>TAP2</em>, <em>DDX60</em>, <em>IFIT5</em>, <em>APOL6</em>, and <em>IFI6</em>) predicted symptomatic infection with reasonable accuracy (area under the curve = 0.84). Notably, adaptive immune responses, including T-cell activation and cytokine signaling, differed substantially between children and adults. Our findings suggest that early measurement of interferon-stimulated gene expression may help identify individuals at risk of developing symptomatic COVID-19.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 1","pages":"Article 106664"},"PeriodicalIF":11.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-19DOI: 10.1016/j.jinf.2025.106659
TianYuan Zhu , JiaYu Guo , Dong Zhang , Li Weng , JinMin Peng , QiWen Yang , Bin Du
Objectives
To compare the clinical utility of DNA- and RNA-metagenomic next-generation sequencing (mNGS) for pathogen detection in lower respiratory tract infections (LRTIs), and evaluate strategies to optimize RNA-mNGS performance.
Methods
We retrospectively analyzed 82 patients with suspected LRTI undergoing simultaneous DNA-mNGS and RNA-mNGS testing. The concordance of two methods in detecting microorganisms was assessed. Performance in detecting causative pathogens was compared using multi-label classification metrics. Impacts of RNA-mNGS workflow adjustments were evaluated using mock samples.
Results
In a total of 196 microbial detections, DNA-mNGS and RNA-mNGS showed poor overall agreement (Cohen’s κ=0.166, p<0.01). In identifying causative pathogens, RNA-mNGS demonstrated significantly higher precision (1.00 vs. 0.50, p<0.05) and F1 scores (0.80 vs. 0.67, p<0.05) compared to DNA-mNGS. DNA-mNGS possessed higher sensitivity for bacteria, fungi, and atypical pathogens, while RNA-mNGS excelled in detecting RNA viruses. Improved RNA-mNGS sensitivity and significant DNA-RNA read correlations were observed in causative pathogens at high abundance. Neither homogenization nor increased sequencing depth improved RNA-mNGS testing.
Conclusions
DNA-mNGS and RNA-mNGS exhibited low overall consistency. However, RNA-mNGS showed superior precision in identifying causative pathogens in LRTI and additional capacity for RNA virus detections, while DNA-mNGS possessed essential sensitivity for low abundance pathogens.
{"title":"A comparative study of DNA- and RNA-metagenomic next-generation sequencing for pathogen detection in lower respiratory tract infections","authors":"TianYuan Zhu , JiaYu Guo , Dong Zhang , Li Weng , JinMin Peng , QiWen Yang , Bin Du","doi":"10.1016/j.jinf.2025.106659","DOIUrl":"10.1016/j.jinf.2025.106659","url":null,"abstract":"<div><h3>Objectives</h3><div>To compare the clinical utility of DNA- and RNA-metagenomic next-generation sequencing (mNGS) for pathogen detection in lower respiratory tract infections (LRTIs), and evaluate strategies to optimize RNA-mNGS performance.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 82 patients with suspected LRTI undergoing simultaneous DNA-mNGS and RNA-mNGS testing. The concordance of two methods in detecting microorganisms was assessed. Performance in detecting causative pathogens was compared using multi-label classification metrics. Impacts of RNA-mNGS workflow adjustments were evaluated using mock samples.</div></div><div><h3>Results</h3><div>In a total of 196 microbial detections, DNA-mNGS and RNA-mNGS showed poor overall agreement (Cohen’s κ=0.166, p<0.01). In identifying causative pathogens, RNA-mNGS demonstrated significantly higher precision (1.00 vs. 0.50, p<0.05) and F1 scores (0.80 vs. 0.67, p<0.05) compared to DNA-mNGS. DNA-mNGS possessed higher sensitivity for bacteria, fungi, and atypical pathogens, while RNA-mNGS excelled in detecting RNA viruses. Improved RNA-mNGS sensitivity and significant DNA-RNA read correlations were observed in causative pathogens at high abundance. Neither homogenization nor increased sequencing depth improved RNA-mNGS testing.</div></div><div><h3>Conclusions</h3><div>DNA-mNGS and RNA-mNGS exhibited low overall consistency. However, RNA-mNGS showed superior precision in identifying causative pathogens in LRTI and additional capacity for RNA virus detections, while DNA-mNGS possessed essential sensitivity for low abundance pathogens.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106659"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-19DOI: 10.1016/j.jinf.2025.106661
Lina Wang , Zhongyuan Zhao , Yuchi Zhao , Shengjie Dong , Shangxiang Feng , Li Cao , Kun Song
Objectives
The aim of this meta-analysis was to assess the diagnostic performance of metagenomic next-generation sequencing and targeted next-generation sequencing for periprosthetic joint infection (PJI).
Background
Next-generation sequencing (NGS) is increasingly used for diagnosing periprosthetic joint infection (PJI), but its clinical utility remains poorly defined. Discrepancies between metagenomic NGS (mNGS) and targeted NGS (tNGS) results pose a significant clinical challenge for PJI diagnosis. To address this, we conducted a systematic review and meta-analysis comparing the diagnostic accuracy of mNGS and tNGS for PJI.
Methods
This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus from inception through June 1, 2025. Two reviewers independently extracted data and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the hierarchical summary receiver operating characteristic curve (AUC) were calculated.
Results
Following screening and eligibility assessment, 23 studies were included in the analysis. The pooled sensitivity and specificity for diagnosing PJI were 0.89 (95% CI: 0.84–0.93) and 0.92 (95% CI: 0.89–0.95) for mNGS, and 0.84 (95% CI: 0.74–0.91) and 0.97 (95% CI: 0.88–0.99) for tNGS. The DORs were 58.56 (95% CI: 38.41–89.26) for mNGS and 106.67 (95% CI: 40.93–278.00) for tNGS. The areas under the summary receiver-operating characteristic curves (AUCs) were 0.935 (95% CI: 0.90–0.95) for mNGS and 0.911 (95% CI: 0.85–0.95) for tNGS. Comparisons of DOR and AUC between mNGS and tNGS revealed no statistically significant differences (P > 0.05).
Conclusions
This meta-analysis indicates that mNGS demonstrates higher sensitivity and a numerically greater AUC than tNGS for diagnosing PJI, with acceptable specificity, although the difference in AUC was not statistically significant. Conversely, tNGS exhibits higher specificity and DOR, alongside acceptable sensitivity, making it valuable for confirming PJI. Overall, the diagnostic accuracy of both next-generation sequencing (NGS) methods is comparable, with each possessing distinct advantages and limitations.
{"title":"Comparative diagnostic accuracy of metagenomic next-generation sequencing and targeted next-generation sequencing for periprosthetic joint infection: A systematic review and meta-analysis","authors":"Lina Wang , Zhongyuan Zhao , Yuchi Zhao , Shengjie Dong , Shangxiang Feng , Li Cao , Kun Song","doi":"10.1016/j.jinf.2025.106661","DOIUrl":"10.1016/j.jinf.2025.106661","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this meta-analysis was to assess the diagnostic performance of metagenomic next-generation sequencing and targeted next-generation sequencing for periprosthetic joint infection (PJI).</div></div><div><h3>Background</h3><div>Next-generation sequencing (NGS) is increasingly used for diagnosing periprosthetic joint infection (PJI), but its clinical utility remains poorly defined. Discrepancies between metagenomic NGS (mNGS) and targeted NGS (tNGS) results pose a significant clinical challenge for PJI diagnosis. To address this, we conducted a systematic review and meta-analysis comparing the diagnostic accuracy of mNGS and tNGS for PJI.</div></div><div><h3>Methods</h3><div>This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus from inception through June 1, 2025. Two reviewers independently extracted data and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the hierarchical summary receiver operating characteristic curve (AUC) were calculated.</div></div><div><h3>Results</h3><div>Following screening and eligibility assessment, 23 studies were included in the analysis. The pooled sensitivity and specificity for diagnosing PJI were 0.89 (95% CI: 0.84–0.93) and 0.92 (95% CI: 0.89–0.95) for mNGS, and 0.84 (95% CI: 0.74–0.91) and 0.97 (95% CI: 0.88–0.99) for tNGS. The DORs were 58.56 (95% CI: 38.41–89.26) for mNGS and 106.67 (95% CI: 40.93–278.00) for tNGS. The areas under the summary receiver-operating characteristic curves (AUCs) were 0.935 (95% CI: 0.90–0.95) for mNGS and 0.911 (95% CI: 0.85–0.95) for tNGS. Comparisons of DOR and AUC between mNGS and tNGS revealed no statistically significant differences (P > 0.05).</div></div><div><h3>Conclusions</h3><div>This meta-analysis indicates that mNGS demonstrates higher sensitivity and a numerically greater AUC than tNGS for diagnosing PJI, with acceptable specificity, although the difference in AUC was not statistically significant. Conversely, tNGS exhibits higher specificity and DOR, alongside acceptable sensitivity, making it valuable for confirming PJI. Overall, the diagnostic accuracy of both next-generation sequencing (NGS) methods is comparable, with each possessing distinct advantages and limitations.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106661"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-12DOI: 10.1016/j.jinf.2025.106655
Bryan E. Cummings , Emily M. Stucke , Drissa Coulibaly , Jonathan G. Lawton , Rafal S. Sobota , Abdoulaye Kassoum Kone , Bourama Kane , Bouréima Guindo , Bourama Tangara , Mody Sissoko , Fayçal Maiga , Karim Traore , Aichatou Diawara , Amidou Traore , Ali Thera , Antoine Dara , Amadou Niangaly , Modibo Daou , Issa Diarra , Youssouf Tolo , Mark A. Travassos
Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (fikk, phist, and surf) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.
{"title":"Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes","authors":"Bryan E. Cummings , Emily M. Stucke , Drissa Coulibaly , Jonathan G. Lawton , Rafal S. Sobota , Abdoulaye Kassoum Kone , Bourama Kane , Bouréima Guindo , Bourama Tangara , Mody Sissoko , Fayçal Maiga , Karim Traore , Aichatou Diawara , Amidou Traore , Ali Thera , Antoine Dara , Amadou Niangaly , Modibo Daou , Issa Diarra , Youssouf Tolo , Mark A. Travassos","doi":"10.1016/j.jinf.2025.106655","DOIUrl":"10.1016/j.jinf.2025.106655","url":null,"abstract":"<div><div><em>Plasmodium falciparum</em> is the most virulent <em>Plasmodium</em> species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (<em>fikk</em>, <em>phist</em>, and <em>surf</em>) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106655"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-13DOI: 10.1016/j.jinf.2025.106657
Justin de Brabander , David S.Y. Ong , Olaf L. Cremer , Lieuwe D.J. Bos , Hessel Peters-Sengers , Tom van der Poll
Objectives
We aimed to compare host response profiles between sepsis patients who develop cytomegalovirus (CMV) reactivation (reactivators) and those who do not (non-reactivators).
Methods
We performed a nested case-control study in CMV-seropositive sepsis patients from two Dutch ICUs. Reactivators (plasma CMV ≥100 IU/ml) were matched 1:1 to non-reactivators, based on length of stay until reactivation, disease severity, and other relevant criteria. We analysed 32 plasma biomarkers and whole-blood gene expression on the day of CMV reactivation (or matched time point for non-reactivators), three days prior, and at ICU admission.
Results
We compared 81 reactivators with 81 matched non-reactivators. In reactivators, six soluble immune checkpoint regulators increased longitudinally from three days before to the day of CMV viraemia onset. In contrast, biomarkers reflecting cytokine release, endothelial activation, coagulation, inflammation and organ damage remained stable. Structural equation modelling identified inhibitory checkpoint regulation as the only variable independently associated with CMV reactivation. Gene expression analysis three days before reactivation revealed upregulation of innate immunity, haemostasis, and CMV-related pathways, alongside downregulation of adaptive immunity and cytokine signalling pathways.
Conclusions
CMV reactivation in sepsis is preceded by broad immune dysregulation. These data provide insight into antiviral immune mechanisms that are impaired prior to reactivation and may inform preventive strategies.
{"title":"Cytomegalovirus reactivation and the host immune response in patients with sepsis","authors":"Justin de Brabander , David S.Y. Ong , Olaf L. Cremer , Lieuwe D.J. Bos , Hessel Peters-Sengers , Tom van der Poll","doi":"10.1016/j.jinf.2025.106657","DOIUrl":"10.1016/j.jinf.2025.106657","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to compare host response profiles between sepsis patients who develop cytomegalovirus (CMV) reactivation (reactivators) and those who do not (non-reactivators).</div></div><div><h3>Methods</h3><div>We performed a nested case-control study in CMV-seropositive sepsis patients from two Dutch ICUs. Reactivators (plasma CMV ≥100 IU/ml) were matched 1:1 to non-reactivators, based on length of stay until reactivation, disease severity, and other relevant criteria. We analysed 32 plasma biomarkers and whole-blood gene expression on the day of CMV reactivation (or matched time point for non-reactivators), three days prior, and at ICU admission.</div></div><div><h3>Results</h3><div>We compared 81 reactivators with 81 matched non-reactivators. In reactivators, six soluble immune checkpoint regulators increased longitudinally from three days before to the day of CMV viraemia onset. In contrast, biomarkers reflecting cytokine release, endothelial activation, coagulation, inflammation and organ damage remained stable. Structural equation modelling identified inhibitory checkpoint regulation as the only variable independently associated with CMV reactivation. Gene expression analysis three days before reactivation revealed upregulation of innate immunity, haemostasis, and CMV-related pathways, alongside downregulation of adaptive immunity and cytokine signalling pathways.</div></div><div><h3>Conclusions</h3><div>CMV reactivation in sepsis is preceded by broad immune dysregulation. These data provide insight into antiviral immune mechanisms that are impaired prior to reactivation and may inform preventive strategies.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106657"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-15DOI: 10.1016/j.jinf.2025.106660
Christina Mertens , Diana Reuter , Anand Ruban Agarvas , Judith Schenz , Bastian Winkelhausen , Anna Hafner , Christoph Kahlert , Maximilian Dietrich , Mascha O. Fiedler-Kalenka , Markus A. Weigand , Martina U. Muckenthaler , Dania Fischer
Background
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. In critically ill patients, iron biomarkers are closely linked to outcomes; yet the mechanistic role of iron metabolism in sepsis progression remains unclear.
Method
To address this knowledge gap, we conducted a longitudinal clinical study in 20 sepsis patients, tracking plasma iron biomarkers together with monocyte function and iron content over five consecutive days following sepsis onset. Some patients required red blood cell transfusions during the study period.
Results
We show that anemia of inflammation is an early and prominent feature of sepsis hallmarked by iron sequestration in blood monocytes, reduced plasma iron levels and anemia. Importantly, increased iron levels in monocytes are detected already at day one following the sepsis diagnosis and the degree of iron accumulation directly correlates with sepsis severity. High monocytic iron levels further correlate with decreased human leukocyte antigen DR (HLA-DR) expression on day one, suggestive of monocyte immunosuppression. Furthermore, in iron-loaded septic monocytes mRNA levels of the non-transferrin bound iron (NTBI) transporter ZRT/IRT-like Protein 8 were significantly increased, suggesting enhanced uptake of non-transferrin bound iron that may arise from hemolysis. Interestingly, we also show that the total iron binding capacity is an important predictor of sepsis mortality, while transfusions did not correlate with an altered iron and/or inflammatory status.
Conclusions
The study highlights that early iron accumulation in monocytes is a hallmark of sepsis and is closely linked to disease severity and progression. We expect that improved insights into iron metabolism in sepsis patients may pave the way to improving therapeutic options that balance iron levels and their effects on organ functions in the future.
{"title":"Monocyte iron load correlates with immune suppression and sepsis severity: A longitudinal analysis","authors":"Christina Mertens , Diana Reuter , Anand Ruban Agarvas , Judith Schenz , Bastian Winkelhausen , Anna Hafner , Christoph Kahlert , Maximilian Dietrich , Mascha O. Fiedler-Kalenka , Markus A. Weigand , Martina U. Muckenthaler , Dania Fischer","doi":"10.1016/j.jinf.2025.106660","DOIUrl":"10.1016/j.jinf.2025.106660","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. In critically ill patients, iron biomarkers are closely linked to outcomes; yet the mechanistic role of iron metabolism in sepsis progression remains unclear.</div></div><div><h3>Method</h3><div>To address this knowledge gap, we conducted a longitudinal clinical study in 20 sepsis patients, tracking plasma iron biomarkers together with monocyte function and iron content over five consecutive days following sepsis onset. Some patients required red blood cell transfusions during the study period.</div></div><div><h3>Results</h3><div>We show that anemia of inflammation is an early and prominent feature of sepsis hallmarked by iron sequestration in blood monocytes, reduced plasma iron levels and anemia. Importantly, increased iron levels in monocytes are detected already at day one following the sepsis diagnosis and the degree of iron accumulation directly correlates with sepsis severity. High monocytic iron levels further correlate with decreased human leukocyte antigen DR (HLA-DR) expression on day one, suggestive of monocyte immunosuppression. Furthermore, in iron-loaded septic monocytes mRNA levels of the non-transferrin bound iron (NTBI) transporter ZRT/IRT-like Protein 8 were significantly increased, suggesting enhanced uptake of non-transferrin bound iron that may arise from hemolysis. Interestingly, we also show that the total iron binding capacity is an important predictor of sepsis mortality, while transfusions did not correlate with an altered iron and/or inflammatory status.</div></div><div><h3>Conclusions</h3><div>The study highlights that early iron accumulation in monocytes is a hallmark of sepsis and is closely linked to disease severity and progression. We expect that improved insights into iron metabolism in sepsis patients may pave the way to improving therapeutic options that balance iron levels and their effects on organ functions in the future.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106660"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-18DOI: 10.1016/j.jinf.2025.106662
Steffen Pichlo, Patricia Sanchez Carballo, Maja Reimann, Nika Zielinski, Yassir Adam Shuaib, Niklas Köhler, Sönke Andres, Jan Heyckendorf , Barbara Kalsdorf, Ioana D. Olaru , Helmut J.F. Salzer , Christoph Lange
{"title":"Lipoarabinomannan (LAM) for the diagnosis of tuberculosis from sputum","authors":"Steffen Pichlo, Patricia Sanchez Carballo, Maja Reimann, Nika Zielinski, Yassir Adam Shuaib, Niklas Köhler, Sönke Andres, Jan Heyckendorf , Barbara Kalsdorf, Ioana D. Olaru , Helmut J.F. Salzer , Christoph Lange","doi":"10.1016/j.jinf.2025.106662","DOIUrl":"10.1016/j.jinf.2025.106662","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106662"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database.
Methods
This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching.
Results
A total of 4627, 861, and 532 children aged <24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p<0.001), 0.67 [0.48, 0.94] (p<0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively.
Conclusion
This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.
{"title":"Long-term impact of nirsevimab on prevention of respiratory syncytial virus infection using a real-world global database","authors":"Taito Kitano , Shinya Tsuzuki , Haruhisa Fukuda , Sayaka Yoshida","doi":"10.1016/j.jinf.2025.106652","DOIUrl":"10.1016/j.jinf.2025.106652","url":null,"abstract":"<div><h3>Objective</h3><div>The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database.</div></div><div><h3>Methods</h3><div>This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching.</div></div><div><h3>Results</h3><div>A total of 4627, 861, and 532 children aged <24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p<0.001), 0.67 [0.48, 0.94] (p<0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively.</div></div><div><h3>Conclusion</h3><div>This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106652"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-15DOI: 10.1016/j.jinf.2025.106656
Chen Cui , Jinyi Zhao , Fei Mu , Dahua Wang , Yamei Li , Meng Tang , Kexin Sun , Rui Gong , Zhen Yan , Jingwen Wang
Objectives
Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase clinical data to predict 28-day mortality by integrating longitudinal trends and addressing comorbidity-driven heterogeneity.
Methods
The BSI Heterogeneity Score (BHScore) was developed using machine learning on longitudinal clinical data (first 7 days post-culture) from 2524 BSI patients at Xijing Hospital. The model uses interpretable methods to establish comorbidity-stratified thresholds (global, renal disease, liver disease, metastatic malignancy) to enhance prediction accuracy.
Results
The BHScore demonstrated superior discriminatory performance (area under the receiver operating characteristic curve: 0.81–0.91) and temporal stability compared to established scores including the Sequential Organ Failure Assessment (SOFA), representing an improvement of 10% to 25%. Our analysis revealed that coagulation biomarkers have greater prognostic significance in the malignancy subgroup, inflammatory thresholds are more sensitive in the liver disease subgroup, and urea levels exhibit U-shaped mortality curves in the renal disease subgroup. To support clinical application, a freely accessible web tool has been developed.
Conclusions
The BHScore enables the early identification of high-risk BSI patients with diverse comorbidities using straightforward clinical indicators, facilitating timely and targeted interventions to reduce mortality.
{"title":"Interpretable machine learning based comorbidity specific mortality risk score for bloodstream infections","authors":"Chen Cui , Jinyi Zhao , Fei Mu , Dahua Wang , Yamei Li , Meng Tang , Kexin Sun , Rui Gong , Zhen Yan , Jingwen Wang","doi":"10.1016/j.jinf.2025.106656","DOIUrl":"10.1016/j.jinf.2025.106656","url":null,"abstract":"<div><h3>Objectives</h3><div>Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase clinical data to predict 28-day mortality by integrating longitudinal trends and addressing comorbidity-driven heterogeneity.</div></div><div><h3>Methods</h3><div>The BSI Heterogeneity Score (BHScore) was developed using machine learning on longitudinal clinical data (first 7 days post-culture) from 2524 BSI patients at Xijing Hospital. The model uses interpretable methods to establish comorbidity-stratified thresholds (global, renal disease, liver disease, metastatic malignancy) to enhance prediction accuracy.</div></div><div><h3>Results</h3><div>The BHScore demonstrated superior discriminatory performance (area under the receiver operating characteristic curve: 0.81–0.91) and temporal stability compared to established scores including the Sequential Organ Failure Assessment (SOFA), representing an improvement of 10% to 25%. Our analysis revealed that coagulation biomarkers have greater prognostic significance in the malignancy subgroup, inflammatory thresholds are more sensitive in the liver disease subgroup, and urea levels exhibit U-shaped mortality curves in the renal disease subgroup. To support clinical application, a freely accessible web tool has been developed.</div></div><div><h3>Conclusions</h3><div>The BHScore enables the early identification of high-risk BSI patients with diverse comorbidities using straightforward clinical indicators, facilitating timely and targeted interventions to reduce mortality.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106656"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-30DOI: 10.1016/j.jinf.2025.106646
Jiajia Zhang , Juncheng Cai , Changhai Liu , Marco Túlio Dos Santos Costa , Tao Ren , Libin Chen
{"title":"The epidemic pattern of a chikungunya outbreak in China exhibits a three-stage migratory trend","authors":"Jiajia Zhang , Juncheng Cai , Changhai Liu , Marco Túlio Dos Santos Costa , Tao Ren , Libin Chen","doi":"10.1016/j.jinf.2025.106646","DOIUrl":"10.1016/j.jinf.2025.106646","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106646"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}