Pavithra Daulagala,Benjamin J Cowling,Hui-Ling Yen
{"title":"Response to Letter to the Editor regarding the immunogenicity of enhanced influenza vaccines in inducing neuraminidase inhibition antibodies.","authors":"Pavithra Daulagala,Benjamin J Cowling,Hui-Ling Yen","doi":"10.1093/infdis/jiag043","DOIUrl":"https://doi.org/10.1093/infdis/jiag043","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033831","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}
Eric Henrique Roma,Fabielle Marques-Santos,Alinne Rangel Dos Santos Renzetti,Luciana Fernandes Portela,Filipe Pereira da Costa,Alejandro Marcel Hasslocher-Moreno,Marcelo Teixeira de Holanda,Luiz Henrique Conde Sangenis,Andréa Rodrigues da Costa,Joseli Lannes-Vieira,Tania Cremonini de Araujo-Jorge,Roberto Rodrigues Ferreira,Roberto Magalhães Saraiva,Maria da Glória Bonecini-Almeida
BACKGROUNDChagas disease (ChD), a major public health concern in Latin America, requires better understanding of molecular mechanisms driving disease progression and identifying biomarkers.OBJECTIVEWe investigated circulating microRNAs associated with ChD susceptibility and chronic Chagas cardiomyopathy (CCC) progression.METHODSIn a cross-sectional study with 150 ChD patients (46 indeterminate, 104 CCC) and 42 non-ChD controls, we performed microRNA sequencing, and differentiated expressed microRNAs (DEMs) were submitted to in silico functional analyses.RESULTSWe identified 40 DEMs between ChD patients and controls, highlighting upregulated miR-143-3p and miR-223-3p, and downregulated miR-486-5p and miR-3960 in ChD patients. These miRNAs showed involvement in immune response and cardiovascular signaling pathways. MiR-6734-5p, miR-1285-5p, miR-10527-5p and miR-1228-5p tended to be upregulated, while miR-30c-3p tended to be downregulated in severe compared to mild CCC patients.CONCLUSIONThis study provides evidence for specific microRNA dysregulation in ChD, highlighting their potential as biomarkers of ChD susceptibility and CCC severity.
{"title":"Transcriptome analysis of circulating microRNAs associated with Chagas disease susceptibility and chronic Chagas cardiomyopathy severity.","authors":"Eric Henrique Roma,Fabielle Marques-Santos,Alinne Rangel Dos Santos Renzetti,Luciana Fernandes Portela,Filipe Pereira da Costa,Alejandro Marcel Hasslocher-Moreno,Marcelo Teixeira de Holanda,Luiz Henrique Conde Sangenis,Andréa Rodrigues da Costa,Joseli Lannes-Vieira,Tania Cremonini de Araujo-Jorge,Roberto Rodrigues Ferreira,Roberto Magalhães Saraiva,Maria da Glória Bonecini-Almeida","doi":"10.1093/infdis/jiag021","DOIUrl":"https://doi.org/10.1093/infdis/jiag021","url":null,"abstract":"BACKGROUNDChagas disease (ChD), a major public health concern in Latin America, requires better understanding of molecular mechanisms driving disease progression and identifying biomarkers.OBJECTIVEWe investigated circulating microRNAs associated with ChD susceptibility and chronic Chagas cardiomyopathy (CCC) progression.METHODSIn a cross-sectional study with 150 ChD patients (46 indeterminate, 104 CCC) and 42 non-ChD controls, we performed microRNA sequencing, and differentiated expressed microRNAs (DEMs) were submitted to in silico functional analyses.RESULTSWe identified 40 DEMs between ChD patients and controls, highlighting upregulated miR-143-3p and miR-223-3p, and downregulated miR-486-5p and miR-3960 in ChD patients. These miRNAs showed involvement in immune response and cardiovascular signaling pathways. MiR-6734-5p, miR-1285-5p, miR-10527-5p and miR-1228-5p tended to be upregulated, while miR-30c-3p tended to be downregulated in severe compared to mild CCC patients.CONCLUSIONThis study provides evidence for specific microRNA dysregulation in ChD, highlighting their potential as biomarkers of ChD susceptibility and CCC severity.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"263 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021517","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}
Jennifer C Zhong, Shuyi Zhong, Lisa Touyon, Faith Ho, Niki Y M Au, Samuel M S Cheng, Dennis K M Ip, Malik Peiris, Emily T Martin, Sarah Cobey, Sook-San Wong, Nancy H L Leung, Benjamin J Cowling
Background Repeated annual influenza vaccination has been associated with attenuated immune responses and reduced clinical effectiveness. Most studies of repeat vaccination immunogenicity have focused on the responses at 30 days after vaccination. As influenza did not circulate in Hong Kong for over two years during the COVID-19 pandemic, we were able to investigate vaccine responses in the absence of infections. Methods In this community-based cohort study in Hong Kong, we investigated the impact of repeated annual influenza vaccination on antibody titer boosting and waning rates of 8 contemporary vaccine strains over two years in 2021/22 and 2022/23, using hemagglutination inhibition assays. We estimated the impact of repeat vaccination on mean-fold rises in titer from before to after vaccination, and on post-vaccination titers. We investigated differences by vaccination history in antibody titer waning rates after day 14 post-vaccination using a power law model. Results We found differences in post-vaccination geometric mean and mean-fold rises in titers against several vaccine strains in repeat vaccinees in 2022/23 compared to 2021/22. However, although participants with higher vaccination uptake had significantly slower antibody waning after 2021/22 vaccination against A/Victoria/2570/2019, B/Phuket/3073/2013, and B/Austria/1359417/2019, they reached similar antibody titers at six months post-vaccination compared to participants with less frequent vaccination history. Conclusions Our findings suggest that repeated influenza vaccination is associated with reduced titer increase at day 14 post-vaccination, but has less impact on antibody levels at six months post-vaccination.
{"title":"Repeat influenza vaccination effects in 2021/22 and 2022/23 in a community-based cohort in Hong Kong","authors":"Jennifer C Zhong, Shuyi Zhong, Lisa Touyon, Faith Ho, Niki Y M Au, Samuel M S Cheng, Dennis K M Ip, Malik Peiris, Emily T Martin, Sarah Cobey, Sook-San Wong, Nancy H L Leung, Benjamin J Cowling","doi":"10.1093/infdis/jiag051","DOIUrl":"https://doi.org/10.1093/infdis/jiag051","url":null,"abstract":"Background Repeated annual influenza vaccination has been associated with attenuated immune responses and reduced clinical effectiveness. Most studies of repeat vaccination immunogenicity have focused on the responses at 30 days after vaccination. As influenza did not circulate in Hong Kong for over two years during the COVID-19 pandemic, we were able to investigate vaccine responses in the absence of infections. Methods In this community-based cohort study in Hong Kong, we investigated the impact of repeated annual influenza vaccination on antibody titer boosting and waning rates of 8 contemporary vaccine strains over two years in 2021/22 and 2022/23, using hemagglutination inhibition assays. We estimated the impact of repeat vaccination on mean-fold rises in titer from before to after vaccination, and on post-vaccination titers. We investigated differences by vaccination history in antibody titer waning rates after day 14 post-vaccination using a power law model. Results We found differences in post-vaccination geometric mean and mean-fold rises in titers against several vaccine strains in repeat vaccinees in 2022/23 compared to 2021/22. However, although participants with higher vaccination uptake had significantly slower antibody waning after 2021/22 vaccination against A/Victoria/2570/2019, B/Phuket/3073/2013, and B/Austria/1359417/2019, they reached similar antibody titers at six months post-vaccination compared to participants with less frequent vaccination history. Conclusions Our findings suggest that repeated influenza vaccination is associated with reduced titer increase at day 14 post-vaccination, but has less impact on antibody levels at six months post-vaccination.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056090","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}
Yanling Liu,Winston T Chu,Syed Qasim Gilani,Daniel B Woodburn,David X Liu,Akhil A Vinithakumari,Nejra Isic,Amber Boshinski,Donna L Perry,Amanda Hischack,Jeffrey Solomon,Ian Crozier,C Paul Morris
The liver is a key target of pathogenic orthomarburgviruses and orthoebolaviruses, with injury common in severe filovirid disease, yet high-resolution histopathologic quantification is lacking. We addressed this by deploying deep learning (DL) models for pixel-level quantitative analysis of digitized liver pathology slides in lethal rhesus monkey (RM) models of Marburg virus (MARV) and two Ebola virus (EBOV) variants, Makona and Kikwit. Our DL model segmented arteries, veins, bile ducts, and hepatic necrosis, achieving interobserver variability in necrosis segmentation comparable to three pathologists. DL-quantified liver necrosis correlated with exposure virus (f=6.61, p=.006) and was highest in MARV-exposed RMs (11.0%). While filovirid-exposed RMs showed elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP), only ALT levels correlated with necrosis severity. Necrosis localization differed: portal tract-proximate after MARV exposure and central vein-proximate after EBOV exposure. This proof-of-concept work enables future large-scale retrospective "meta-pathologic" analyses.
{"title":"Machine learning-enabled quantification of hepatocellular necrosis in the liver after lethal Marburg and Ebola virus exposures.","authors":"Yanling Liu,Winston T Chu,Syed Qasim Gilani,Daniel B Woodburn,David X Liu,Akhil A Vinithakumari,Nejra Isic,Amber Boshinski,Donna L Perry,Amanda Hischack,Jeffrey Solomon,Ian Crozier,C Paul Morris","doi":"10.1093/infdis/jiag040","DOIUrl":"https://doi.org/10.1093/infdis/jiag040","url":null,"abstract":"The liver is a key target of pathogenic orthomarburgviruses and orthoebolaviruses, with injury common in severe filovirid disease, yet high-resolution histopathologic quantification is lacking. We addressed this by deploying deep learning (DL) models for pixel-level quantitative analysis of digitized liver pathology slides in lethal rhesus monkey (RM) models of Marburg virus (MARV) and two Ebola virus (EBOV) variants, Makona and Kikwit. Our DL model segmented arteries, veins, bile ducts, and hepatic necrosis, achieving interobserver variability in necrosis segmentation comparable to three pathologists. DL-quantified liver necrosis correlated with exposure virus (f=6.61, p=.006) and was highest in MARV-exposed RMs (11.0%). While filovirid-exposed RMs showed elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP), only ALT levels correlated with necrosis severity. Necrosis localization differed: portal tract-proximate after MARV exposure and central vein-proximate after EBOV exposure. This proof-of-concept work enables future large-scale retrospective \"meta-pathologic\" analyses.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015185","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":"When Time Is of the Essence: Hepatitis C Virus RNA Point-of-Care Testing in 15 Minutes Becomes a Reality.","authors":"Tanya L Applegate,Jason Grebely","doi":"10.1093/infdis/jiaf652","DOIUrl":"https://doi.org/10.1093/infdis/jiaf652","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015269","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}
BACKGROUNDDespite advances in anthelmintic therapy, there are currently no effective treatments for schistosomiasis-induced liver fibrosis. Previous studies have reported elevated marginal zone B and B1 cell specific protein (MZB1) expression in fibrotic diseases, but its function remains unclear, and its role in schistosomiasis has not been investigated. This study aimed to explore the function and mechanism of MZB1 in Schistosoma japonicum infection.METHODSWe evaluated the expression of Mzb1 in the liver and spleen of Schistosoma-infected mice using methods such as Western blot, qPCR, and immunohistochemistry. We also employed adeno-associated virus (AAV) to knock down Mzb1 gene expression, assessing the role of Mzb1 in the progression of schistosomiasis and its downstream pathways. Additionally, in vivo experiments were conducted using downstream endoplasmic reticulum stress agonists and inhibitors to evaluate the role of this pathway in the progression of schistosomiasis.RESULTSOur findings demonstrated that Mzb1 was significantly upregulated in the liver and spleen tissues of infected mice. Knockdown of Mzb1 markedly reduced liver fibrosis and splenomegaly. Mzb1 was predominantly expressed in CD20-positive B cells and was found to activate endoplasmic reticulum (ER) stress. Inhibition of ER stress alleviated liver fibrosis and splenomegaly, while activation of ER stress exacerbated these pathological conditions and reversed the protective effects of Mzb1 knockdown.CONCLUSIONSWe identified Mzb1 as a key factor that promotes liver fibrosis and splenomegaly in schistosomiasis through the activation of ER stress. This novel pathogenic mechanism may provide a potential therapeutic target for the treatment of schistosomiasis-induced liver fibrosis.
{"title":"Mzb1 Promotes Progression of Schistosomiasis by Inducing Endoplasmic Reticulum Stress.","authors":"Lanyue Pan,Hongyan Kong,Dandan Xiang,Guo Li,Zhilin Zeng,Shuaiwen Huang,Xin Xu,Jingjing Li,Jiaquan Huang","doi":"10.1093/infdis/jiaf639","DOIUrl":"https://doi.org/10.1093/infdis/jiaf639","url":null,"abstract":"BACKGROUNDDespite advances in anthelmintic therapy, there are currently no effective treatments for schistosomiasis-induced liver fibrosis. Previous studies have reported elevated marginal zone B and B1 cell specific protein (MZB1) expression in fibrotic diseases, but its function remains unclear, and its role in schistosomiasis has not been investigated. This study aimed to explore the function and mechanism of MZB1 in Schistosoma japonicum infection.METHODSWe evaluated the expression of Mzb1 in the liver and spleen of Schistosoma-infected mice using methods such as Western blot, qPCR, and immunohistochemistry. We also employed adeno-associated virus (AAV) to knock down Mzb1 gene expression, assessing the role of Mzb1 in the progression of schistosomiasis and its downstream pathways. Additionally, in vivo experiments were conducted using downstream endoplasmic reticulum stress agonists and inhibitors to evaluate the role of this pathway in the progression of schistosomiasis.RESULTSOur findings demonstrated that Mzb1 was significantly upregulated in the liver and spleen tissues of infected mice. Knockdown of Mzb1 markedly reduced liver fibrosis and splenomegaly. Mzb1 was predominantly expressed in CD20-positive B cells and was found to activate endoplasmic reticulum (ER) stress. Inhibition of ER stress alleviated liver fibrosis and splenomegaly, while activation of ER stress exacerbated these pathological conditions and reversed the protective effects of Mzb1 knockdown.CONCLUSIONSWe identified Mzb1 as a key factor that promotes liver fibrosis and splenomegaly in schistosomiasis through the activation of ER stress. This novel pathogenic mechanism may provide a potential therapeutic target for the treatment of schistosomiasis-induced liver fibrosis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005027","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}
Sylvia M LaCourse,Jaclyn N Escudero,Wendy E Whatney,Krista N Krish,Arijita Subuddhi,Sara Belauret,Rachel A Pearson,Lisa Marie Cranmer,Jerphason Mecha,Daniel Matemo,Elizabeth Maleche-Obimbo,John Kinuthia,Barbra A Richardson,Grace John-Stewart,Cheryl L Day
BACKGROUNDReduced early life IFN-γ production capacity may limit sensitivity of IFN-γ release assays (IGRAs) to detect M. tuberculosis (Mtb)-specific responses in young children. Measurement of non-interferon-γ (IFN-γ) cytokine responses may improve detection of these responses in children.METHODSPBMCs from HIV-exposed uninfected (cHEU) and HIV-unexposed (cHUU) children in Western Kenya collected between 6-10 weeks, and at 12 and 24 months of age were incubated overnight with Mtb-specific CFP-10/ESAT-6 peptides and staphylococcus enterotoxin B (SEB, positive control). CD4 and CD8 T cell expression of IFN-γ and non-IFN-γ (IL-2, TNF) cytokines was measured by flow cytometry.RESULTSAmong 213 children, 28.6% had CFP-10/ESAT-6 CD4 and/or CD8 responses up to 24 months of age. No children with a positive Mtb-specific response had a reported known TB exposure. More children exhibited Mtb-specific non-IFN-γ+ (IL-2+ and/or TNF+) responses than IFN-γ+ responses (26.3% vs. 10.3%, p<0.001), including 18.3% identified by non-IFN-γ+ responses alone (non-IFN-γ+ alone 18.3% vs. IFN-γ+ alone 2.4%, p <0.001). Proportion of children with Mtb-specific responses were similar regardless of HIV exposure (cHEU 31.5% vs. cHUU 25.5%, p=0.33). At 6-10 weeks of age, children were more likely to have non-IFN-γ+ vs. IFN-γ+ responses to SEB (positive control) (96.3% vs. 77.8%, p=0.004); however, by 24 months of age 100% of children had both IFN-γ+ and non-IFN-γ+ SEB responses.CONCLUSIONMtb-specific CD4/CD8 responses were common among young Kenyan children up to 24 months of age, despite limited reported TB exposures. Non-IFN-γ+ T cell cytokine expression identified more children than IFN-γ+ who would be potentially missed by commercially available IGRAs.
{"title":"Mtb-specific CFP-10/ESAT-6 CD4 and CD8 T cell non-IFN-γ+ responses are common in young Kenyan children despite low reported TB exposure.","authors":"Sylvia M LaCourse,Jaclyn N Escudero,Wendy E Whatney,Krista N Krish,Arijita Subuddhi,Sara Belauret,Rachel A Pearson,Lisa Marie Cranmer,Jerphason Mecha,Daniel Matemo,Elizabeth Maleche-Obimbo,John Kinuthia,Barbra A Richardson,Grace John-Stewart,Cheryl L Day","doi":"10.1093/infdis/jiag039","DOIUrl":"https://doi.org/10.1093/infdis/jiag039","url":null,"abstract":"BACKGROUNDReduced early life IFN-γ production capacity may limit sensitivity of IFN-γ release assays (IGRAs) to detect M. tuberculosis (Mtb)-specific responses in young children. Measurement of non-interferon-γ (IFN-γ) cytokine responses may improve detection of these responses in children.METHODSPBMCs from HIV-exposed uninfected (cHEU) and HIV-unexposed (cHUU) children in Western Kenya collected between 6-10 weeks, and at 12 and 24 months of age were incubated overnight with Mtb-specific CFP-10/ESAT-6 peptides and staphylococcus enterotoxin B (SEB, positive control). CD4 and CD8 T cell expression of IFN-γ and non-IFN-γ (IL-2, TNF) cytokines was measured by flow cytometry.RESULTSAmong 213 children, 28.6% had CFP-10/ESAT-6 CD4 and/or CD8 responses up to 24 months of age. No children with a positive Mtb-specific response had a reported known TB exposure. More children exhibited Mtb-specific non-IFN-γ+ (IL-2+ and/or TNF+) responses than IFN-γ+ responses (26.3% vs. 10.3%, p<0.001), including 18.3% identified by non-IFN-γ+ responses alone (non-IFN-γ+ alone 18.3% vs. IFN-γ+ alone 2.4%, p <0.001). Proportion of children with Mtb-specific responses were similar regardless of HIV exposure (cHEU 31.5% vs. cHUU 25.5%, p=0.33). At 6-10 weeks of age, children were more likely to have non-IFN-γ+ vs. IFN-γ+ responses to SEB (positive control) (96.3% vs. 77.8%, p=0.004); however, by 24 months of age 100% of children had both IFN-γ+ and non-IFN-γ+ SEB responses.CONCLUSIONMtb-specific CD4/CD8 responses were common among young Kenyan children up to 24 months of age, despite limited reported TB exposures. Non-IFN-γ+ T cell cytokine expression identified more children than IFN-γ+ who would be potentially missed by commercially available IGRAs.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015190","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":"CXCR6 in the Blood Is Not the Liver: Clarifying NK-Cell 'Homing' and Post-Cure ADCC Imprints in Acute Hepatitis C.","authors":"Anxin Wen","doi":"10.1093/infdis/jiag044","DOIUrl":"https://doi.org/10.1093/infdis/jiag044","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"123 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005028","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}
Silvia Lucena Lage,Joseph M Rocco,Cihan Oguz,Francisco Otaizo-Carrasquero,Adam Rupert,Kristin L Boswell,Brian P Epling,Logan Cook,Eduardo Pinheiro Amaral,Elizabeth Laidlaw,Frances Galindo,Richard A Koup,Princy Kumar,Rita Poon,Glenn W Wortmann,Andrea Lisco,Maura Manion,Irini Sereti
BACKGROUNDDespite the efficacy of therapeutics and vaccines in reducing risk of severe COVID-19, SARS-CoV-2 infections continue to occur and rebound symptoms after initial improvement has been well-described. The mechanisms driving COVID-19 rebound remain unclear.METHODSCritical inflammatory responses were assessed by Imagestream, flow cytometry and single-cell RNA sequencing in peripheral blood mononuclear cells from vaccinated individuals presenting with early [EA, 3 days post-infection (PI), n=6] or late (LA, 8 days PI, n=6) acute symptoms and clinical rebound (rebound, 16 days PI, n=8), as well as healthy volunteers (HV, n=7).RESULTSAn overall decline in key inflammatory responses is observed in groups with longer time from symptom onset when compared to EA infection. However, RNA sequencing revealed a partial resurgence of inflammatory, stress and antiviral responses during clinical rebound, with a unique cluster of monocytes with greater activation of antigen presentation pathways and type-I IFN signaling. Monocytes from patients with rebound COVID-19 also showed elevated inflammasome activation when compared to HV, along with an accumulation of oxidized lipids and decreased levels of glutathione, both hallmarks of the oxidative stress response. Inflammatory measurements positively associated with serum SARS-CoV-2 nucleocapsid antigen and inversely correlated with adaptive immune responses, suggesting adaptive immunity limits inflammation in patients with rebound.CONCLUSIONSOur findings potentially reflect viral reappearance post-treatment in participants with clinical rebound and outline mechanisms why rebound symptoms are typically milder than during acute presentations. Extending the antiviral treatment period and/or targeting inflammatory pathways could potentially prevent virological rebound or help mitigate associated symptoms.
{"title":"Inflammasome activation and oxidative stress in SARS-CoV-2 infection and symptomatic rebound.","authors":"Silvia Lucena Lage,Joseph M Rocco,Cihan Oguz,Francisco Otaizo-Carrasquero,Adam Rupert,Kristin L Boswell,Brian P Epling,Logan Cook,Eduardo Pinheiro Amaral,Elizabeth Laidlaw,Frances Galindo,Richard A Koup,Princy Kumar,Rita Poon,Glenn W Wortmann,Andrea Lisco,Maura Manion,Irini Sereti","doi":"10.1093/infdis/jiag037","DOIUrl":"https://doi.org/10.1093/infdis/jiag037","url":null,"abstract":"BACKGROUNDDespite the efficacy of therapeutics and vaccines in reducing risk of severe COVID-19, SARS-CoV-2 infections continue to occur and rebound symptoms after initial improvement has been well-described. The mechanisms driving COVID-19 rebound remain unclear.METHODSCritical inflammatory responses were assessed by Imagestream, flow cytometry and single-cell RNA sequencing in peripheral blood mononuclear cells from vaccinated individuals presenting with early [EA, 3 days post-infection (PI), n=6] or late (LA, 8 days PI, n=6) acute symptoms and clinical rebound (rebound, 16 days PI, n=8), as well as healthy volunteers (HV, n=7).RESULTSAn overall decline in key inflammatory responses is observed in groups with longer time from symptom onset when compared to EA infection. However, RNA sequencing revealed a partial resurgence of inflammatory, stress and antiviral responses during clinical rebound, with a unique cluster of monocytes with greater activation of antigen presentation pathways and type-I IFN signaling. Monocytes from patients with rebound COVID-19 also showed elevated inflammasome activation when compared to HV, along with an accumulation of oxidized lipids and decreased levels of glutathione, both hallmarks of the oxidative stress response. Inflammatory measurements positively associated with serum SARS-CoV-2 nucleocapsid antigen and inversely correlated with adaptive immune responses, suggesting adaptive immunity limits inflammation in patients with rebound.CONCLUSIONSOur findings potentially reflect viral reappearance post-treatment in participants with clinical rebound and outline mechanisms why rebound symptoms are typically milder than during acute presentations. Extending the antiviral treatment period and/or targeting inflammatory pathways could potentially prevent virological rebound or help mitigate associated symptoms.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005032","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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