Tanya E Libby, Angela Karani, Kirkby D Tickell, Donald Akech, Benson Singa, Doreen Rwigi, Kevin Kariuki, Nancy Onamu, Derrick Ounga, James A Berkley, Judd L Walson, J Anthony G Scott, Patricia B Pavlinac
Background Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. Methods We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1,398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% confidence intervals for the intervention, adjusting for enrollment site. Results Overall, 1,253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared to the placebo group (171/696 [24.6%]; p = 0.4) and did not differ at month 3 (65.6% vs 67.0%; PR:0.98[0.90, 1.06]) or month 6 (66.7% vs 66.5%; PR:1.00[0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] vs 32/256 [12.5%]; PR:1.06[0.86, 1.66]) or month 6 (41/245 [16.7%] vs 43/243 [17.6%]; PR:1.01[0.69,1.49]). Conclusions Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.
{"title":"The effect of a 5-day course of azithromycin on Streptococcus pneumoniae carriage and antimicrobial resistance among Kenyan children discharged from hospital","authors":"Tanya E Libby, Angela Karani, Kirkby D Tickell, Donald Akech, Benson Singa, Doreen Rwigi, Kevin Kariuki, Nancy Onamu, Derrick Ounga, James A Berkley, Judd L Walson, J Anthony G Scott, Patricia B Pavlinac","doi":"10.1093/infdis/jiag028","DOIUrl":"https://doi.org/10.1093/infdis/jiag028","url":null,"abstract":"Background Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. Methods We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1,398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% confidence intervals for the intervention, adjusting for enrollment site. Results Overall, 1,253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared to the placebo group (171/696 [24.6%]; p = 0.4) and did not differ at month 3 (65.6% vs 67.0%; PR:0.98[0.90, 1.06]) or month 6 (66.7% vs 66.5%; PR:1.00[0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] vs 32/256 [12.5%]; PR:1.06[0.86, 1.66]) or month 6 (41/245 [16.7%] vs 43/243 [17.6%]; PR:1.01[0.69,1.49]). Conclusions Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986328","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}
James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances
Background As persons with HIV (PWH) live longer, interactions between HIV, aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWoH), PWH with undetectable virus (PWHU) (≤50 copies/mL), and PWH with detectable virus (PHWD) (>50 copies/mL). Cross-sectional and longitudinal data were included. Methods Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWoH, 264 PWHU and 84 PWHD with a total of 841 sessions. A series of generalized additive mixed models explored group differences in the relationship between age and cognition, age and regional brain volumes, and interactions between age and brain volumes on cognition. Results PWoH and PWHU exhibited similar change in cognitive performance with age, while PWHD exhibited a steeper decline compared to both. While both PWH groups had significantly smaller regional brain volumes compared to PWoH, the slopes of volume loss with age were similar across all groups except in the lentiform regions. Smaller brain volumes and increased age interacted for greater cognitive decline in PWHD. Conclusion PWH who achieve viral suppression do not exhibit accelerated decline in cognition or brain volumes compared to PWoH, while PWHD may be at an increased risk for accelerated cognitive decline. These findings highlight the clinical importance of managing viral load in aging PWH and suggest that once viral suppression is achieved, changes to brain integrity are not accelerated compared to PWoH.
{"title":"Longitudinal changes in cognition and brain imaging in persons with HIV","authors":"James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances","doi":"10.1093/infdis/jiag029","DOIUrl":"https://doi.org/10.1093/infdis/jiag029","url":null,"abstract":"Background As persons with HIV (PWH) live longer, interactions between HIV, aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWoH), PWH with undetectable virus (PWHU) (≤50 copies/mL), and PWH with detectable virus (PHWD) (>50 copies/mL). Cross-sectional and longitudinal data were included. Methods Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWoH, 264 PWHU and 84 PWHD with a total of 841 sessions. A series of generalized additive mixed models explored group differences in the relationship between age and cognition, age and regional brain volumes, and interactions between age and brain volumes on cognition. Results PWoH and PWHU exhibited similar change in cognitive performance with age, while PWHD exhibited a steeper decline compared to both. While both PWH groups had significantly smaller regional brain volumes compared to PWoH, the slopes of volume loss with age were similar across all groups except in the lentiform regions. Smaller brain volumes and increased age interacted for greater cognitive decline in PWHD. Conclusion PWH who achieve viral suppression do not exhibit accelerated decline in cognition or brain volumes compared to PWoH, while PWHD may be at an increased risk for accelerated cognitive decline. These findings highlight the clinical importance of managing viral load in aging PWH and suggest that once viral suppression is achieved, changes to brain integrity are not accelerated compared to PWoH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986327","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}
Tess E Peterson,Virginia S Hahn,Ruin Moaddel,Min Zhu,Jinshui Fan,Supriyo De,Sabina A Haberlen,Frank J Palella,Michael Plankey,Joel S Bader,Joao A C Lima,Robert E Gerszten,Jerome I Rotter,Gregory D Kirk,Damani A Piggott,Luigi Ferrucci,Joseph B Margolick,Todd T Brown,Wendy S Post,Katherine C Wu
BACKGROUNDPeople with HIV (PWH) are at higher risk of myocardial fibrosis and subsequent heart failure (HF) compared to people without HIV (PWOH). Mechanisms underlying this risk and its specificity to PWH are unclear.METHODSWe measured 2594 proteins in plasma obtained concurrently with cardiovascular magnetic resonance imaging among 342 PWH and PWOH. We estimated associations with HIV serostatus and myocardial fibrosis (elevated extracellular volume fraction, ECV ≥30% among women, ≥28% among men) using multivariable regression. Among an independent community-based cohort, we estimated associations between the identified signature and time to incident HF.RESULTSParticipants were age 55±6 years, 25% female, 61% PWH (88% on antiretroviral therapy, 74% undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and one cluster of 42 proteins that were higher among PWH vs. PWOH and positively associated with elevated ECV, independent of risk factors (FDR<0.05). Among an independent cohort of 3223 PWOH (age 68±9 years; 52% female; 118 incident HF cases over 9.8±1.4 years), we found this protein cluster and 34 of 39 individual proteins were associated with time to incident HF. This signature was statistically enriched for T cell activation, TNF signaling, ephrin signaling, and tissue maintenance and repair.CONCLUSIONWe identified an HIV-related proteomic signature associated with myocardial fibrosis regardless of HIV serostatus and that predicted incident HF among the general population. Our results identify several novel associations related to specific immune processes that may contribute to risk of myocardial fibrosis and subsequent HF among both PWH and PWOH.
{"title":"HIV-Associated Proteomic Signature of Myocardial Fibrosis and Incident Heart Failure.","authors":"Tess E Peterson,Virginia S Hahn,Ruin Moaddel,Min Zhu,Jinshui Fan,Supriyo De,Sabina A Haberlen,Frank J Palella,Michael Plankey,Joel S Bader,Joao A C Lima,Robert E Gerszten,Jerome I Rotter,Gregory D Kirk,Damani A Piggott,Luigi Ferrucci,Joseph B Margolick,Todd T Brown,Wendy S Post,Katherine C Wu","doi":"10.1093/infdis/jiag013","DOIUrl":"https://doi.org/10.1093/infdis/jiag013","url":null,"abstract":"BACKGROUNDPeople with HIV (PWH) are at higher risk of myocardial fibrosis and subsequent heart failure (HF) compared to people without HIV (PWOH). Mechanisms underlying this risk and its specificity to PWH are unclear.METHODSWe measured 2594 proteins in plasma obtained concurrently with cardiovascular magnetic resonance imaging among 342 PWH and PWOH. We estimated associations with HIV serostatus and myocardial fibrosis (elevated extracellular volume fraction, ECV ≥30% among women, ≥28% among men) using multivariable regression. Among an independent community-based cohort, we estimated associations between the identified signature and time to incident HF.RESULTSParticipants were age 55±6 years, 25% female, 61% PWH (88% on antiretroviral therapy, 74% undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and one cluster of 42 proteins that were higher among PWH vs. PWOH and positively associated with elevated ECV, independent of risk factors (FDR<0.05). Among an independent cohort of 3223 PWOH (age 68±9 years; 52% female; 118 incident HF cases over 9.8±1.4 years), we found this protein cluster and 34 of 39 individual proteins were associated with time to incident HF. This signature was statistically enriched for T cell activation, TNF signaling, ephrin signaling, and tissue maintenance and repair.CONCLUSIONWe identified an HIV-related proteomic signature associated with myocardial fibrosis regardless of HIV serostatus and that predicted incident HF among the general population. Our results identify several novel associations related to specific immune processes that may contribute to risk of myocardial fibrosis and subsequent HF among both PWH and PWOH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949816","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}
Edward N Kankaka,Stephen Tomusange,Taddeo Kityamuweesi,Gabriel Quiros,Nicholas DiRico,Adam A Capoferri,Owen Baker,Erin E Brown,Jernelle Miller,Sharada Saraf,Charles Kirby,Briana Lynch,Jada Hackman,Craig Martens,Thomas C Quinn,Eileen P Scully,Amjad Khan,Art F Y Poon,Jessica L Prodger,Ronald M Galiwango,Steven J Reynolds,Andrew D Redd
BACKGROUNDAccurate estimation of HIV viremic time is valuable for understanding reservoir dynamics, and informing cure trials. Traditional approaches rely on serological assays or CD4 counts, which can lack quantitative precision. Sequence-based estimates using diversity in pre-treatment plasma RNA address this limitation, but are increasingly limited in the era of immediate ART initiation.METHODSWe developed Bayesian models to predict viremic time using sequence diversity from HIV reservoir sequences in two cohorts from Rakai, Uganda and Sweden. We computed six diversity metrics for gp41, RT, and matrix p17 regions. We fitted 36 Bayesian models per region using slope-fitting and weighting strategies, and evaluated them based on predictive accuracy and model diagnostics. The best-performing models were validated on participants with known diagnosis dates, but unknown seroconversion dates.RESULTSReservoir diversity increased with viremic time across all metrics. Models based on diversity from unique RT and gp41 sequences performed well, with improved predictions when combined, particularly using simple diversity metrics such as nucleotide diversity and mean TN93 distances. In validation, these models produced estimates and credible intervals that aligned with known HIV diagnosis dates; and inclusion of weights using log-transformed sequence counts increased the precision of prediction. Models using matrix p17, complex diversity metrics, or identical sequences showed weaker performance.CONCLUSIONSWe present a new Bayesian approach to estimate HIV viremic time from reservoir sequences with associated uncertainty estimates. Our prediction approach works across subtypes and chronic infection, uses simple diversity metrics, and may support research on HIV reservoir dynamics and cure.
{"title":"Estimating HIV-1 Viremic Time from Reservoir Sequence Diversity with Uncertainty Quantification.","authors":"Edward N Kankaka,Stephen Tomusange,Taddeo Kityamuweesi,Gabriel Quiros,Nicholas DiRico,Adam A Capoferri,Owen Baker,Erin E Brown,Jernelle Miller,Sharada Saraf,Charles Kirby,Briana Lynch,Jada Hackman,Craig Martens,Thomas C Quinn,Eileen P Scully,Amjad Khan,Art F Y Poon,Jessica L Prodger,Ronald M Galiwango,Steven J Reynolds,Andrew D Redd","doi":"10.1093/infdis/jiag020","DOIUrl":"https://doi.org/10.1093/infdis/jiag020","url":null,"abstract":"BACKGROUNDAccurate estimation of HIV viremic time is valuable for understanding reservoir dynamics, and informing cure trials. Traditional approaches rely on serological assays or CD4 counts, which can lack quantitative precision. Sequence-based estimates using diversity in pre-treatment plasma RNA address this limitation, but are increasingly limited in the era of immediate ART initiation.METHODSWe developed Bayesian models to predict viremic time using sequence diversity from HIV reservoir sequences in two cohorts from Rakai, Uganda and Sweden. We computed six diversity metrics for gp41, RT, and matrix p17 regions. We fitted 36 Bayesian models per region using slope-fitting and weighting strategies, and evaluated them based on predictive accuracy and model diagnostics. The best-performing models were validated on participants with known diagnosis dates, but unknown seroconversion dates.RESULTSReservoir diversity increased with viremic time across all metrics. Models based on diversity from unique RT and gp41 sequences performed well, with improved predictions when combined, particularly using simple diversity metrics such as nucleotide diversity and mean TN93 distances. In validation, these models produced estimates and credible intervals that aligned with known HIV diagnosis dates; and inclusion of weights using log-transformed sequence counts increased the precision of prediction. Models using matrix p17, complex diversity metrics, or identical sequences showed weaker performance.CONCLUSIONSWe present a new Bayesian approach to estimate HIV viremic time from reservoir sequences with associated uncertainty estimates. Our prediction approach works across subtypes and chronic infection, uses simple diversity metrics, and may support research on HIV reservoir dynamics and cure.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907843","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}
Marc J T Blaauw,Adriana Navas,Victoria Rios Vásquez,Nadira Vadaq,Marvin A H Berrevoets,Twan Otten,Wilhelm A J W Vos,Louise E van Eekeren,Albert L Groenendijk,Gert Weijers,Esther Lutgens,Hans J P M Koenen,Marien I de Jonge,Mihai G Netea,Joost H W Rutten,Andre J A M van der Ven,Niels P Riksen
BACKGROUNDPeople living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD), but the immunological mechanisms driving plaque formation remain unclear. This study investigated the association between peripheral immune cell subsets and carotid atherosclerotic plaques in PLHIV without prior clinical ASCVD.METHODSIn this multi-center cross-sectional study, virally suppressed PLHIV receiving antiretroviral therapy were enrolled from two Dutch cohorts: a discovery cohort (n= 994) and a validation cohort (n= 200). Between November 2019 and October 2021, participants underwent carotid ultrasound imaging to assess plaques using standardized criteria. Immune profiling was performed using high-dimensional flow cytometry of 355 immune cell populations. Associations with plaque were analyzed using linear regression adjusted for relevant confounders, and key findings were validated in the second cohort. Transcriptomic profiles of main cell populations were evaluated using deconvoluted bulk RNA sequencing to identify differential expression and pathway enrichment.RESULTSCarotid plaques were present in 584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort. Plaques were associated with higher counts of several CD8+ T cell subsets, particularly PD-1-expressing cytotoxic T cells with an interferon secretion profile (CD8TC1PD1+). Transcriptomic analysis of CD8+ T cells revealed downregulated mitochondrial function and upregulated type 1 interferon and epidermal growth factor receptor (EGFR) signaling, indicating a senescent phenotype.CONCLUSIONSCD8+ T cell senescence may contribute to early atherosclerotic plaque formation in PLHIV. Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT03994835.
{"title":"Functional and transcriptional senescence profiles of CD8+ T cells associate with the presence of carotid plaques in people living with HIV.","authors":"Marc J T Blaauw,Adriana Navas,Victoria Rios Vásquez,Nadira Vadaq,Marvin A H Berrevoets,Twan Otten,Wilhelm A J W Vos,Louise E van Eekeren,Albert L Groenendijk,Gert Weijers,Esther Lutgens,Hans J P M Koenen,Marien I de Jonge,Mihai G Netea,Joost H W Rutten,Andre J A M van der Ven,Niels P Riksen","doi":"10.1093/infdis/jiag018","DOIUrl":"https://doi.org/10.1093/infdis/jiag018","url":null,"abstract":"BACKGROUNDPeople living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD), but the immunological mechanisms driving plaque formation remain unclear. This study investigated the association between peripheral immune cell subsets and carotid atherosclerotic plaques in PLHIV without prior clinical ASCVD.METHODSIn this multi-center cross-sectional study, virally suppressed PLHIV receiving antiretroviral therapy were enrolled from two Dutch cohorts: a discovery cohort (n= 994) and a validation cohort (n= 200). Between November 2019 and October 2021, participants underwent carotid ultrasound imaging to assess plaques using standardized criteria. Immune profiling was performed using high-dimensional flow cytometry of 355 immune cell populations. Associations with plaque were analyzed using linear regression adjusted for relevant confounders, and key findings were validated in the second cohort. Transcriptomic profiles of main cell populations were evaluated using deconvoluted bulk RNA sequencing to identify differential expression and pathway enrichment.RESULTSCarotid plaques were present in 584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort. Plaques were associated with higher counts of several CD8+ T cell subsets, particularly PD-1-expressing cytotoxic T cells with an interferon secretion profile (CD8TC1PD1+). Transcriptomic analysis of CD8+ T cells revealed downregulated mitochondrial function and upregulated type 1 interferon and epidermal growth factor receptor (EGFR) signaling, indicating a senescent phenotype.CONCLUSIONSCD8+ T cell senescence may contribute to early atherosclerotic plaque formation in PLHIV. Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT03994835.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907844","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}
Dan-Yu Lin, Melissa A Mischell, Xinyu Zhang, Katie R Mollan, Ning Zhang, Dinelka Nanyakkara, Jessica R Keys, Becky Straub, David Wohl, William Fischer
In a prospective cohort study of 2,960 non-hospitalized adults with acute SARS-CoV-2 infection, older age, female sex, rural residence, high BMI, greater acute infection severity, chronic lung disease, and poorer general health at baseline were associated with higher risk and severity of postacute sequelae. Recent vaccination was associated with lower postacute sequelae risk and severity, while antiviral therapy was not.
{"title":"Incidence and Severity of Postacute Sequelae of SARS-CoV-2 Infection in the Omicron Era: A Prospective Cohort Study","authors":"Dan-Yu Lin, Melissa A Mischell, Xinyu Zhang, Katie R Mollan, Ning Zhang, Dinelka Nanyakkara, Jessica R Keys, Becky Straub, David Wohl, William Fischer","doi":"10.1093/infdis/jiag026","DOIUrl":"https://doi.org/10.1093/infdis/jiag026","url":null,"abstract":"In a prospective cohort study of 2,960 non-hospitalized adults with acute SARS-CoV-2 infection, older age, female sex, rural residence, high BMI, greater acute infection severity, chronic lung disease, and poorer general health at baseline were associated with higher risk and severity of postacute sequelae. Recent vaccination was associated with lower postacute sequelae risk and severity, while antiviral therapy was not.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920335","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}
Katherine A Davies, Stephen R Welch, JoAnn D Coleman-McCray, Teresa E Sorvillo, Virginia Aida-Ficken, Shilpi Jain, César G Albariño, Biao He, Christina F Spiropoulou, Jessica R Spengler
Marburgviruses cause severe hemorrhagic disease in humans, yet characterization of rodent models for pathogenesis and medical countermeasure development remains limited. Here, we investigated clinical course, blood chemistry, viral dissemination, and mucosal viral detection in inbred BALB/c and outbred CD-1 mice infected with MA-Marburg virus (MARV)/Angola or MA-Ravn virus (RAVV) to further mouse model development. Regardless of virus or mouse strain, infection resulted in widespread viral dissemination in animals sampled up to 5 days post-infection. However, in animals followed to study end, MA-MARV/Angola caused severe disease and lethality in both mouse strains, whereas MA-RAVV caused only mild or asymptomatic infection.
{"title":"Characterization of mouse-adapted Marburg and Ravn viruses in inbred BALB/c and outbred CD-1 mice","authors":"Katherine A Davies, Stephen R Welch, JoAnn D Coleman-McCray, Teresa E Sorvillo, Virginia Aida-Ficken, Shilpi Jain, César G Albariño, Biao He, Christina F Spiropoulou, Jessica R Spengler","doi":"10.1093/infdis/jiag019","DOIUrl":"https://doi.org/10.1093/infdis/jiag019","url":null,"abstract":"Marburgviruses cause severe hemorrhagic disease in humans, yet characterization of rodent models for pathogenesis and medical countermeasure development remains limited. Here, we investigated clinical course, blood chemistry, viral dissemination, and mucosal viral detection in inbred BALB/c and outbred CD-1 mice infected with MA-Marburg virus (MARV)/Angola or MA-Ravn virus (RAVV) to further mouse model development. Regardless of virus or mouse strain, infection resulted in widespread viral dissemination in animals sampled up to 5 days post-infection. However, in animals followed to study end, MA-MARV/Angola caused severe disease and lethality in both mouse strains, whereas MA-RAVV caused only mild or asymptomatic infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920334","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}
Joshua N Monteith,Emma L Ledger,Michelle N Chamoun,Ian R Henderson,Joanna B Goldberg,Daniel Smith,Daniel C Chambers,Simon H Apte,Timothy J Wells
BACKGROUNDPeople with cystic fibrosis (pwCF) are susceptible to chronic lung infections, particularly with Pseudomonas aeruginosa. During infection, a subset of patients develop cloaking antibodies (cAb) specific to O-antigen lipopolysaccharide (LPS) that impair complement-mediated bactericidal killing. These antibodies associate with worse disease and their removal via plasmapheresis has been used as a successful treatment for multi-drug-resistant P. aeruginosa. Whether a similar mechanism of antibody-mediated serum resistance exists towards common polysaccharide antigen (CPA) LPS is unknown.METHODSForty-two serum samples and 63 matched P. aeruginosa isolates were collected from pwCF. The titres of antibodies specific to CPA in patient sera were determined, and the ability of these antibodies to inhibit serum-mediated killing of P. aeruginosa was assessed.RESULTSDespite widespread anti-CPA antibodies, only one serum-strain pair showed evidence of complement inhibition. Patient serum IgG and IgA responses to CPA were elevated in 86% and 69% of sera, respectively. Further, 69% of pwCF were colonised with CPA-expressing isolates. Despite high prevalence of elevated anti-CPA antibodies, only one patient had antibodies capable of inhibiting complement killing of their cognate P. aeruginosa. This isolate, CFP3A, had significantly higher expression of CPA than all other strains. Complement-mediated killing towards it was inhibited by anti-CPA antibodies in a titre dependent manner.CONCLUSIONThis investigation reveals that although antibody specific for CPA is prevalent in pwCF, it cannot inhibit complement-killing of the majority of CPA expressing strains. Thus, when treating Pseudomonas by removing cloaking antibodies, it is unlikely that CPA-specific antibodies will also need to be eliminated.
{"title":"Treatment of Pseudomonas by removal of cloaking antibodies; is common polysaccharide antigen a factor?","authors":"Joshua N Monteith,Emma L Ledger,Michelle N Chamoun,Ian R Henderson,Joanna B Goldberg,Daniel Smith,Daniel C Chambers,Simon H Apte,Timothy J Wells","doi":"10.1093/infdis/jiag002","DOIUrl":"https://doi.org/10.1093/infdis/jiag002","url":null,"abstract":"BACKGROUNDPeople with cystic fibrosis (pwCF) are susceptible to chronic lung infections, particularly with Pseudomonas aeruginosa. During infection, a subset of patients develop cloaking antibodies (cAb) specific to O-antigen lipopolysaccharide (LPS) that impair complement-mediated bactericidal killing. These antibodies associate with worse disease and their removal via plasmapheresis has been used as a successful treatment for multi-drug-resistant P. aeruginosa. Whether a similar mechanism of antibody-mediated serum resistance exists towards common polysaccharide antigen (CPA) LPS is unknown.METHODSForty-two serum samples and 63 matched P. aeruginosa isolates were collected from pwCF. The titres of antibodies specific to CPA in patient sera were determined, and the ability of these antibodies to inhibit serum-mediated killing of P. aeruginosa was assessed.RESULTSDespite widespread anti-CPA antibodies, only one serum-strain pair showed evidence of complement inhibition. Patient serum IgG and IgA responses to CPA were elevated in 86% and 69% of sera, respectively. Further, 69% of pwCF were colonised with CPA-expressing isolates. Despite high prevalence of elevated anti-CPA antibodies, only one patient had antibodies capable of inhibiting complement killing of their cognate P. aeruginosa. This isolate, CFP3A, had significantly higher expression of CPA than all other strains. Complement-mediated killing towards it was inhibited by anti-CPA antibodies in a titre dependent manner.CONCLUSIONThis investigation reveals that although antibody specific for CPA is prevalent in pwCF, it cannot inhibit complement-killing of the majority of CPA expressing strains. Thus, when treating Pseudomonas by removing cloaking antibodies, it is unlikely that CPA-specific antibodies will also need to be eliminated.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"177 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907582","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}
Yuya Ito,Tracey-Ann Hoeltermann,Seher Anjum,Londyn Robinson,Jessica S Little,Michael Kiritsy,Julie M Steinbrink,Andrea Finocchi,Lorne W Walker,Robin K Avery,Shmuel Shoham,Omer E Beaird,Song C Ong,Cornelius N Van Dam,Ina Stephens,Ambar Haleem,Peter R Williamson
BACKGROUNDPost-infectious inflammatory response syndrome (PIIRS) is recognized as a cause of neurologic deterioration in previously healthy patients with cryptococcal meningoencephalitis (CM). However, data on non-human immunodeficiency virus (HIV), immunosuppressed patients remain limited.METHODSBetween July 2018 and April 2025, 13 non-HIV immunosuppressed patients with CM who subsequently developed PIIRS were included. Clinical features, Karnofsky performance scores, cerebrospinal fluid (CSF) parameters, and magnetic resonance imaging (MRI) findings were compared at PIIRS diagnosis and during follow-up after corticosteroid therapy.RESULTSAll patients showed evidence of CNS inflammation, including abnormal CSF, MRI findings, and neurological symptoms such as altered mental status or visual/hearing loss. Corticosteroid therapy was associated with significant improvements in Karnofsky scores at 1 month (P = .001), with sustained benefit at 6 and twelve months (P = .002); all 10 surviving patients demonstrated resolution of neurological symptoms. CSF inflammatory parameters including white blood cell (WBC) count, protein, and CSF/serum glucose ratio also significantly improved at 1 month. Brain MRI findings also showed a trend toward improvement. All patients remained culture-negative post-PIIRS diagnosis. Three patients died: 1 from complications of alcoholic cirrhosis, the second from liver failure in the setting of systemic lupus erythematosus and immunosuppression, and the third from sepsis after initiation of corticosteroids.CONCLUSIONSCorticosteroids were associated with improvement in neurological status and neuroinflammation in non-HIV, immunosuppressed patients with PIIRS following CM. These findings support its potential role as salvage therapy in this population and highlight the need for systematic data collection or randomized trials to better guide corticosteroid use.
{"title":"Corticosteroid Therapy and Long-Term Outcomes of Post-Infectious Inflammatory Syndrome in Non-HIV Immunosuppressed Cryptococcal Meningitis: A Multicenter Case Series.","authors":"Yuya Ito,Tracey-Ann Hoeltermann,Seher Anjum,Londyn Robinson,Jessica S Little,Michael Kiritsy,Julie M Steinbrink,Andrea Finocchi,Lorne W Walker,Robin K Avery,Shmuel Shoham,Omer E Beaird,Song C Ong,Cornelius N Van Dam,Ina Stephens,Ambar Haleem,Peter R Williamson","doi":"10.1093/infdis/jiaf620","DOIUrl":"https://doi.org/10.1093/infdis/jiaf620","url":null,"abstract":"BACKGROUNDPost-infectious inflammatory response syndrome (PIIRS) is recognized as a cause of neurologic deterioration in previously healthy patients with cryptococcal meningoencephalitis (CM). However, data on non-human immunodeficiency virus (HIV), immunosuppressed patients remain limited.METHODSBetween July 2018 and April 2025, 13 non-HIV immunosuppressed patients with CM who subsequently developed PIIRS were included. Clinical features, Karnofsky performance scores, cerebrospinal fluid (CSF) parameters, and magnetic resonance imaging (MRI) findings were compared at PIIRS diagnosis and during follow-up after corticosteroid therapy.RESULTSAll patients showed evidence of CNS inflammation, including abnormal CSF, MRI findings, and neurological symptoms such as altered mental status or visual/hearing loss. Corticosteroid therapy was associated with significant improvements in Karnofsky scores at 1 month (P = .001), with sustained benefit at 6 and twelve months (P = .002); all 10 surviving patients demonstrated resolution of neurological symptoms. CSF inflammatory parameters including white blood cell (WBC) count, protein, and CSF/serum glucose ratio also significantly improved at 1 month. Brain MRI findings also showed a trend toward improvement. All patients remained culture-negative post-PIIRS diagnosis. Three patients died: 1 from complications of alcoholic cirrhosis, the second from liver failure in the setting of systemic lupus erythematosus and immunosuppression, and the third from sepsis after initiation of corticosteroids.CONCLUSIONSCorticosteroids were associated with improvement in neurological status and neuroinflammation in non-HIV, immunosuppressed patients with PIIRS following CM. These findings support its potential role as salvage therapy in this population and highlight the need for systematic data collection or randomized trials to better guide corticosteroid use.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897516","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}
Background The persistence of immunological memory after immunization against monkeypox virus (MPXV) is unclear. This study assessed MPXV-specific neutralizing antibodies (NAbs) at >2 years from Mpox or Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) vaccination. Methods Retrospective study including individuals with previous Mpox or vaccination with MVA-BN, whose MPXV-specific NAb titers were already assessed at six months from either event at our center. Neutralizing titers were determined at >2 years from Mpox or vaccination by Plaque Reduction Neutralization Test (PRNT) [positive≥1:10] as the maximum dilution with reduction of cytopathic effect of 90% and 50% (IC90-IC50). Groups were compared using chi-square test, Fisher’s exact test or Wilcoxon rank-sum test. Association between titers at >2 years and individuals characteristics was evaluated with ordinal logistic regression. Results Overall, 48 individuals with previous Mpox and 42 vaccinees were included, all were men. At >2 years from Mpox or vaccination, 22/90 (24.44%) and 53/90 (58.8%) had positive NAb titers respectively at IC90 and IC50. At IC50 previous Mpox was associated with positive titers (68.75% vs 47.62%; p=0.042), with univariate analysis associating higher titers at six months to higher titers at >2 years (OR=6.45,95%CI=1.89–22.07;p=0.003). At multivariate analysis, historical smallpox vaccination was associated to higher titers at >2 years (OR=5.37,95%CI=1.31-22.00;p=0.020), whilst previous Mpox was marginally associated (OR=2.08,95%CI=0.94-4.62;p=0.073). Conclusions MPXV-specific NAbs waned at >2 years from previous infection or vaccination, often becoming undetectable. Higher NAb titers at six months (univariate) and prior smallpox vaccination (multivariate) were associated with NAb detection at >2 years, whilst previous Mpox was marginally associated.
背景猴痘病毒（MPXV）免疫后免疫记忆的持久性尚不清楚。本研究评估了mpxv特异性中和抗体（nab）在；接种m痘或改良安卡拉巴伐利亚北欧牛痘（MVA-BN）疫苗2年。方法回顾性研究纳入既往m痘或接种MVA-BN的个体，其mpxv特异性NAb滴度已在我们中心的任何事件发生后6个月进行评估。中和效价在&；gt；通过斑块减少中和试验（PRNT）[阳性≥1:10]作为最大稀释剂，减少90%和50%的细胞病变效应（IC90-IC50），从m痘或接种疫苗2年。组间比较采用卡方检验、Fisher精确检验或Wilcoxon秩和检验。滴度&；gt；采用有序logistic回归评价2年及个体特征。结果共纳入48例既往m痘患者和42例接种者，均为男性。在和gt;接种Mpox或疫苗2年后，22/90（24.44%）和53/90（58.8%）的NAb滴度分别为IC90和IC50阳性。IC50时，既往m痘与阳性滴度相关（68.75% vs 47.62%; p=0.042），单变量分析将6个月时较高的滴度与&；gt时较高的滴度联系起来；2年（OR=6.45,95%CI=1.89 ~ 22.07;p=0.003）。在多变量分析中，历史天花疫苗接种与较高滴度相关。2年（OR=5.37,95%CI=1.31-22.00;p=0.020），而既往m痘患者与m痘相关（OR=2.08,95%CI=0.94-4.62;p=0.073）。结论mpxv特异性nab在&；gt；距离上次感染或接种疫苗2年，通常无法检测到。6个月时较高的NAb滴度（单变量）和先前的天花疫苗接种（多变量）与NAb在&；gt；2年，而以前的m痘有轻微的相关性。
{"title":"A humoral dilemma: reassessing monkeypox virus neutralizing antibodies at more than two years from Mpox or MVA-BN vaccination","authors":"Nicolò Moschetta, Elena Criscuolo, Angelo Roberto Raccagni, Nicolò Capra, Riccardo Lolatto, Gabriele Loi, Diana Canetti, Antonella Castagna, Silvia Nozza, Nicola Clementi","doi":"10.1093/infdis/jiag009","DOIUrl":"https://doi.org/10.1093/infdis/jiag009","url":null,"abstract":"Background The persistence of immunological memory after immunization against monkeypox virus (MPXV) is unclear. This study assessed MPXV-specific neutralizing antibodies (NAbs) at &gt;2 years from Mpox or Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) vaccination. Methods Retrospective study including individuals with previous Mpox or vaccination with MVA-BN, whose MPXV-specific NAb titers were already assessed at six months from either event at our center. Neutralizing titers were determined at &gt;2 years from Mpox or vaccination by Plaque Reduction Neutralization Test (PRNT) [positive≥1:10] as the maximum dilution with reduction of cytopathic effect of 90% and 50% (IC90-IC50). Groups were compared using chi-square test, Fisher’s exact test or Wilcoxon rank-sum test. Association between titers at &gt;2 years and individuals characteristics was evaluated with ordinal logistic regression. Results Overall, 48 individuals with previous Mpox and 42 vaccinees were included, all were men. At &gt;2 years from Mpox or vaccination, 22/90 (24.44%) and 53/90 (58.8%) had positive NAb titers respectively at IC90 and IC50. At IC50 previous Mpox was associated with positive titers (68.75% vs 47.62%; p=0.042), with univariate analysis associating higher titers at six months to higher titers at &gt;2 years (OR=6.45,95%CI=1.89–22.07;p=0.003). At multivariate analysis, historical smallpox vaccination was associated to higher titers at &gt;2 years (OR=5.37,95%CI=1.31-22.00;p=0.020), whilst previous Mpox was marginally associated (OR=2.08,95%CI=0.94-4.62;p=0.073). Conclusions MPXV-specific NAbs waned at &gt;2 years from previous infection or vaccination, often becoming undetectable. Higher NAb titers at six months (univariate) and prior smallpox vaccination (multivariate) were associated with NAb detection at &gt;2 years, whilst previous Mpox was marginally associated.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903728","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}
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