Man Li,Fen Zeng,Wei Chang,Mengyuan Zheng,Xiaojuan Chen,Ziying Wu,Li Liu,Xueshan Xia,Yue Feng
{"title":"Emergence of two new lineages of the cosmopolitan dengue virus serotype 2 in Yunnan, China, 2024.","authors":"Man Li,Fen Zeng,Wei Chang,Mengyuan Zheng,Xiaojuan Chen,Ziying Wu,Li Liu,Xueshan Xia,Yue Feng","doi":"10.1093/infdis/jiaf422","DOIUrl":"https://doi.org/10.1093/infdis/jiaf422","url":null,"abstract":"BACKGROUNDDengue fever has become a significant epidemic in South and Southeast Asia. Recently, Yunnan Province in southwestern China, which borders these regions, has also experienced a significant outbreak. This study aims to investigate the genetic diversity of the dengue virus (DENV) and identify potential sources of transmission in Xishuangbanna, Yunnan Province in 2024.METHODSIn 2024, we investigated 321 suspected cases of dengue fever in Yunnan Province. We screened dengue fever patients using a combination of DENV NS1 antigen and Pan-qPCR methods, and performed serotype typing using specific qPCR. We also performed phylogenetic and molecular clock analyses to understand the genotypes and transmission sources.RESULTSDENV infection was detected in 101 of 321 specimens. Serotype and genotype analysis were performed on 88 of the 98 positive samples. The results showed that 81 cases belonged to the cosmopolitan genotype and cosmopolitan_asian-pacific subtype of DENV serotype 2 (DENV-2), while only 1 case was classified as genotype I and subtype 1L of DENV serotype 1 (DENV-1). Notably, samples within the cosmopolitan_asian-pacific subtype were primarily divided into two distinct lineages. Further analysis of whole genome sequences, focusing on phylogenetic history and spatiotemporal dynamics, indicated that lineage-1 likely originated in Thailand, while lineage-2 may have originated in Cambodia. In addition, we analyzed all available DENV-2 sequences from Yunnan in the GenBank database and found that DENV-2 genotypes in the Xishuangbanna region were more diverse and complex.CONCLUSIONSThis study identifies two new lineages of cosmopolitan DENV-2 in Yunnan, originating from Thailand and Cambodia, respectively.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weifeng Xu,Joseph Antonello,Jennifer Nguyen,Chuying Ma,Ya-Wen Cheng,Kasia Marullo,Katrina Nolan,Ulrike K Buchwald,Heather L Platt,Marie Bonhomme,David C LaFon,Robert L Burton,Moon H Nahm,Roy Helmy
{"title":"Low intrinsic killing activity and no impact of its positivity on phase 3 pneumococcal vaccine adult studies.","authors":"Weifeng Xu,Joseph Antonello,Jennifer Nguyen,Chuying Ma,Ya-Wen Cheng,Kasia Marullo,Katrina Nolan,Ulrike K Buchwald,Heather L Platt,Marie Bonhomme,David C LaFon,Robert L Burton,Moon H Nahm,Roy Helmy","doi":"10.1093/infdis/jiaf427","DOIUrl":"https://doi.org/10.1093/infdis/jiaf427","url":null,"abstract":"BACKGROUNDThe opsonophagocytic assay (OPA) is the gold standard for measuring functional antibody responses to bacterial vaccines. However, antibody-independent bactericidal activities, such as those by antibiotics, could contribute to the killing and thus inflate the measured antibody titer. Because of this, an intrinsic killing (IK) assay is currently required to screen and exclude samples with antibody-independent bactericidal activities.METHODSHere, we utilized multiple Phase 3 studies of V116 (Capvaxive), as well as in vitro antibiotic spiked samples with known OPA titers, to gain in-depth insights regarding the impact and necessity of the IK screening testing.RESULTSOur results show that even at the highest clinically relevant blood concentration, an antibiotic such as amoxicillin only contributes to a titer of about 50 in the antibody-depleted serum sample. Consistent with this, IK-positivity in V116 Phase 3 studies only showed higher geometric mean titers (GMTs) in the pre-vaccinated, baseline population when the GMTs are lower than 320. After vaccination, no significant differences in OPA titers were observed between IK-positive and IK-negative samples. This, combined with the low rate of IK positivity in healthy adults of V116 clinical studies (≤2 % in each study), demonstrated that including IK-positive samples did not alter the relevant clinical assessments of opsonophagocytic activity.CONCLUSIONThus, eliminating the IK assay as a requirement for OPA testing could be considered in healthy adult populations where antibiotic use is well-regulated.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"143 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dagna Constenla,Germain Lonnet,Emmanuel Aris,R K Ramsanjay,Nathalie Servotte,Agnes Mwakingwe-Omari,Hannah Alsdurf,Huifeng Yun
{"title":"Real-world effectiveness of the adjuvanted recombinant zoster vaccine in ≥50-year-old adults with autoimmune diseases.","authors":"Dagna Constenla,Germain Lonnet,Emmanuel Aris,R K Ramsanjay,Nathalie Servotte,Agnes Mwakingwe-Omari,Hannah Alsdurf,Huifeng Yun","doi":"10.1093/infdis/jiaf395","DOIUrl":"https://doi.org/10.1093/infdis/jiaf395","url":null,"abstract":"BACKGROUNDReal-world data on the vaccine effectiveness (VE) of the adjuvanted recombinant zoster vaccine (RZV) to prevent herpes zoster (HZ) among individuals with autoimmune diseases (AIDs) are limited. To address this knowledge gap, we aimed to evaluate the VE of two RZV doses against HZ in ≥50-year-old adults with selected AIDs (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, psoriasis, and psoriatic arthritis).METHODSWe conducted a retrospective matched cohort study using Optum's de-identified Clinformatics® Data Mart Database datasets from January-2018 to December-2021. Patients were matched by AID condition, age, and medication category, then 1:3 by propensity scores that accounted for the likelihood of receiving RZV, adjusted on selected confounders. For each AID, we calculated HZ incidence rates and RZV VE, overall and stratified by age, sex, time interval between two RZV doses, medication category, and time since vaccination.RESULTSThe two-dose cohort included 36,645 RZV-vaccinated and 109,229 unvaccinated patients. Two RZV doses offer protection against HZ in patients with AIDs, with VEs ranging from 48.1% for multiple sclerosis to 77.2% for psoriasis. An overall reduction in HZ incidence from 12.9 (95% confidence interval [CI]: 12.3; 13.5) to 4.3 (95% CI: 3.8; 4.9) per 1,000 person-years among vaccinated individuals was found, corresponding to an overall VE against HZ of 66.3% (95% CI: 61.4; 70.7).CONCLUSIONSOur analysis shows that RZV vaccination prevents HZ in ≥50-year-old adults with selected AIDs, consistent with prior studies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camille M Moore,Elizabeth A Secor,Jamie L Everman,Ana Fairbanks-Mahnke,Nathan Jackson,Elmar Pruesse,Katrina Diener,Andrew Morin,Samuel J Arbes,Leonard B Bacharier,Casper G Bendixsen,Agustin Calatroni,William D Dupont,Glenn T Furuta,Tebeb Gebretsadik,Rebecca S Gruchalla,Ruchi S Gupta,Gurjit K Khurana Hershey,Meyer Kattan,Andrew H Liu,Stephanie J Lussier,Liza Bronner Murrison,Mari Numata,George T O'Connor,Katherine River-Spoljaric,Wanda Phipatanakul,Marc E Rothenberg,Christine M Seroogy,Edward M Zoratti,Sharon Castina,Daniel J Jackson,Carlos A Camargo,Christine C Johnson,Rachel Ethridge,Sima Ramratnam,Lia Stelzig,Stephen J Teach,Alkis G Togias,Patricia C Fulkerson,Tina V Hartert,Max A Seibold
{"title":"The common cold is associated with protection from SARS-CoV-2 Infections.","authors":"Camille M Moore,Elizabeth A Secor,Jamie L Everman,Ana Fairbanks-Mahnke,Nathan Jackson,Elmar Pruesse,Katrina Diener,Andrew Morin,Samuel J Arbes,Leonard B Bacharier,Casper G Bendixsen,Agustin Calatroni,William D Dupont,Glenn T Furuta,Tebeb Gebretsadik,Rebecca S Gruchalla,Ruchi S Gupta,Gurjit K Khurana Hershey,Meyer Kattan,Andrew H Liu,Stephanie J Lussier,Liza Bronner Murrison,Mari Numata,George T O'Connor,Katherine River-Spoljaric,Wanda Phipatanakul,Marc E Rothenberg,Christine M Seroogy,Edward M Zoratti,Sharon Castina,Daniel J Jackson,Carlos A Camargo,Christine C Johnson,Rachel Ethridge,Sima Ramratnam,Lia Stelzig,Stephen J Teach,Alkis G Togias,Patricia C Fulkerson,Tina V Hartert,Max A Seibold","doi":"10.1093/infdis/jiaf374","DOIUrl":"https://doi.org/10.1093/infdis/jiaf374","url":null,"abstract":"BACKGROUNDAdults and children often respond differently to SARS-CoV-2 infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.METHODSUsing case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10,493 longitudinal nasal swabs from 1,156 participants for 21 respiratory pathogens. We performed RNA-sequencing on 147 swabs (N=144 participants) collected prior SARS-CoV-2 infection and 391 swabs (N=165 participants) during and before rhinovirus infection.RESULTSParticipants with rhinovirus infection in the previous 30 days were at 48% lower risk of SARS-CoV-2 infection (aHR:0.52, p=0.034). Among participants with SARS-CoV-2 infection, recent rhinovirus infection was associated with 9.6-fold lower SARS-CoV-2 viral load (p=0.0031). Higher pre-infection expression of 57 genes was associated with lower SARS-CoV-2 viral load, including 24 antiviral defense genes; 22 of these were induced by rhinovirus infections. Relative to adults, children expressed higher levels of the antiviral gene signature (p=0.014) and were at 2.2-fold increased risk for rhinovirus infections.CONCLUSIONSRhinovirus infections, which trigger increased expression of antiviral airway genes, are linked to a lower risk of SARS-CoV-2 infection. Frequent rhinovirus infections may enhance this protective gene profile, partially explaining why children experience milder SARS-CoV-2 infections compared to adults.TRIAL REGISTRATION NUMBERNCT04375761.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Host Immune Response Profiling for the Diagnosis of Infectious Diseases.","authors":"Kimberly E Hanson,Ephraim L Tsalik","doi":"10.1093/infdis/jiaf428","DOIUrl":"https://doi.org/10.1093/infdis/jiaf428","url":null,"abstract":"Recent advances in infectious diseases diagnostics include the development, validation, and commercialization of new tests that measure host gene expression profiles or inflammatory protein concentrations. Interrogating host immune responses may help separate infectious from non-infectious inflammation, differentiate infection types and/or predict sepsis severity/subtype. This review summarizes the current state-of-the art in host response (HR) diagnostics for infectious diseases with a focus on test accuracy. Few studies have assessed the potential impact of HR testing on patient outcomes. We summarize current clinical evidence gaps and describe the types of studies needed to inform optimal integration in clinical practice.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara D Veeken,Katherine C Horton,Rein M G J Houben
{"title":"Authors' response to \"TB prevalence in people tested is a strong predictor of Xpert specificity in community and risk group screening\".","authors":"Lara D Veeken,Katherine C Horton,Rein M G J Houben","doi":"10.1093/infdis/jiaf419","DOIUrl":"https://doi.org/10.1093/infdis/jiaf419","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"291 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicky McCreesh,Indira Govender,Alison D Grant,Palwasha Y Khan
{"title":"TB prevalence in people tested is a strong predictor of Xpert specificity in community and risk group screening.","authors":"Nicky McCreesh,Indira Govender,Alison D Grant,Palwasha Y Khan","doi":"10.1093/infdis/jiaf418","DOIUrl":"https://doi.org/10.1093/infdis/jiaf418","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taraz Samandari, Millicent Achola, Jack N Hutter, Grace Mboya, Walter Otieno, Jia Jin Kee, Yunda Huang, John J Aponte, Christian F Ockenhouse, Cynthia K Lee, Laura Polakowski, Margaret Yacovone, Asa Tapley, Sufia Dadabhai, Nonhlanhla N Mkhize, Haajira Kaldine, Sinethemba Bhebhe, Penny L Moore, John Hural, Nigel Garrett, James G Kublin
{"title":"Plasmodium falciparum Parasitemia Does Not Diminish Neutralizing Antibody Responses After mRNA COVID-19 Booster Vaccination in HIV-infected Adults","authors":"Taraz Samandari, Millicent Achola, Jack N Hutter, Grace Mboya, Walter Otieno, Jia Jin Kee, Yunda Huang, John J Aponte, Christian F Ockenhouse, Cynthia K Lee, Laura Polakowski, Margaret Yacovone, Asa Tapley, Sufia Dadabhai, Nonhlanhla N Mkhize, Haajira Kaldine, Sinethemba Bhebhe, Penny L Moore, John Hural, Nigel Garrett, James G Kublin","doi":"10.1093/infdis/jiaf398","DOIUrl":"https://doi.org/10.1093/infdis/jiaf398","url":null,"abstract":"mRNA vaccines have emerged as powerful tools for the prevention of infectious diseases, but subclinical malaria may reduce vaccine immunogenicity. We evaluated neutralizing antibody responses in asymptomatic HIV-infected adults with and without PCR-confirmed Plasmodium falciparum who received either monovalent mRNA-1273 or bivalent mRNA-1273.222 (WA-1 and BA.4/5) booster vaccines. In previous studies, a 50% pseudovirus inhibitory dose neutralizing antibody (ID50) titer of 1,000 correlated with 96% efficacy in preventing COVID-19. We observed ID50 geometric mean titers >22,000 in both parasitemic and non-parasitemic participants one month after boosting. We conclude that COVID-19 mRNA vaccine antibody responses are unimpaired by concurrent asymptomatic parasitemia.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica A Bryant, Timothy J Straub, Darrell S Pardi, Kevin D Litcofsky, Colleen R Kelly, Meghan E Chafee, Stuart H Cohen, Sahil Khanna, Charles S Berenson, Jennifer Wortman, Matthew Sims, Christopher B Ford, Mary-Jane Lombardo, Barbara H McGovern, Lisa von Moltke, Colleen S Kraft, Matthew R Henn, Brooke R Hasson
{"title":"Comparability of gastrointestinal microbiome and bile acid profiles in patients with first or multiply recurrent Clostridioides difficile infection","authors":"Jessica A Bryant, Timothy J Straub, Darrell S Pardi, Kevin D Litcofsky, Colleen R Kelly, Meghan E Chafee, Stuart H Cohen, Sahil Khanna, Charles S Berenson, Jennifer Wortman, Matthew Sims, Christopher B Ford, Mary-Jane Lombardo, Barbara H McGovern, Lisa von Moltke, Colleen S Kraft, Matthew R Henn, Brooke R Hasson","doi":"10.1093/infdis/jiaf408","DOIUrl":"https://doi.org/10.1093/infdis/jiaf408","url":null,"abstract":"Background Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic. Methods Patients received VOS following symptom resolution after standard-of-care antibiotics. Pre-treatment baseline (within 3 days following antibiotic completion) and week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS. Results rCDI rates through week 8 were similarly low in both frCDI and mrCDI patients (6.5% vs. 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (p>0.05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1. Conclusions These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heather L Teague, Seth Warner, Andrew P Platt, Sydney Stein, Marcos J Ramos-Benitez, Sabrina Ramelli, Shelly Curran, Izabella Lach, Kiana Allen, Heritage Adetola, Trevor Stantliff, Raquel Santana da Cruz, Mahnaz Minai, Heather Kendall, Kevin M Vannella, Derron A Alves, Richard Herbert, Daniel S Chertow, Jeffrey R Strich
{"title":"Elevated Spleen Tyrosine Kinase in Low-Density Neutrophils During Bacterial Sepsis in a Nonhuman Primate Model","authors":"Heather L Teague, Seth Warner, Andrew P Platt, Sydney Stein, Marcos J Ramos-Benitez, Sabrina Ramelli, Shelly Curran, Izabella Lach, Kiana Allen, Heritage Adetola, Trevor Stantliff, Raquel Santana da Cruz, Mahnaz Minai, Heather Kendall, Kevin M Vannella, Derron A Alves, Richard Herbert, Daniel S Chertow, Jeffrey R Strich","doi":"10.1093/infdis/jiaf403","DOIUrl":"https://doi.org/10.1093/infdis/jiaf403","url":null,"abstract":"Background Sepsis is a leading cause of death world-wide. Identifying novel host-directed therapeutic targets may improve sepsis outcomes. Methods Six nonhuman primates were infected with Klebsiella pneumoniae to induce septic shock and provided supportive care for up to 72 hours. Flow cytometry was used to characterize whole blood neutrophils (WBNs) and low-density neutrophils (LDNs) at time (T0), T6, T24, and T48-hours post-infection; and postmortem examination (i.e. necropsy). Dimensional reduction with clustering via FlowSOM and traditional gating strategies were used to compare WBNs to LDNs and delineate spleen tyrosine kinase (SYK) expression across neutrophils subsets. We measured soluble biomarkers of end-organ dysfunction and neutrophil activation and quantified SYK and myeloperoxidase in tissue. Results At T6, we identified populations of active immature WBNs and a population of LDNs not detected at baseline. At T24, neutrophil heterogeneity increased across WBNs and LDNs with differential expression of myeloperoxidase (MPO). Compared to WBNs, LDNs were more activated with increased MPO expression. At T6, SYK expression surged in WBNs and LDNs and SYK+WBNs and LDNs expressed higher levels of MPO and lactoferrin compared to SYK- neutrophils. Circulating levels of SYK+LDNs significantly correlated with serum creatinine levels, indicative of acute kidney injury; prolonged prothrombin time and decreased fibrinogen, indicative of consumptive coagulopathy; and SYK expression in tissues. Conclusions Bacterial sepsis leads to heterogenous populations of circulating neutrophils, including LDNs. Elevated SYK expression in WBNs and LDNs correlates with end-organ dysfunction, highlighting SYK as a potential therapeutic target in bacterial sepsis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}