Pub Date : 2026-01-21DOI: 10.1080/22221751.2025.2610856
Yuanyuan Guo,Jinmin Tian,Peipei Guo,Xin Wang,Bingli Shang,Junying She,Mengjie Yang,George F Gao,Jun Liu
Since its emergence in late 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has continuously threatened human health through constantly arising variants with iterative immune escape abilities. While SARS-CoV-2 variants have been recently classified into six serotypes based on cross-reactive antibody responses, T cell response features against these serotypes remain largely unknown. We evaluated SARS-CoV-2 spike-specific T cell responses among convalescents infected by three different strains (prototype, BA.5.2/BF.7, and XBB/EG.5.1) against SARS-CoV-2 prototype and 15 subvariants covering all six serotypes. Generally, cross-reactive T cells could recognize variants within the same serotype, but they also mounted weaker responses to variants from subsequent serotypes. Serotype I (prototype) convalescents showed lower T cell responses against Omicron variants (Serotype II to IV), with cross-reactive T cell gaps between different serotype strains, i.e. Serotype II > III > IV. Serotype IV (BA.5.2/BF.7) convalescents exhibited weaker T cell responses to Serotype V (XBB/XBB.1.5/XBB.1.16/EG.5.1) strains and even lower responses to Serotype VI (BA.2.86/JN.1) strains. Similarly, Serotype V (XBB) convalescents showed significantly weaker cross-T cell responses to the Serotype VI (BA.2.86) strains than to the Serotype V strains. We also identified key serotype-signature mutations in T cell epitope hotspot regions that could attenuate CD8+ and/or CD4+ T cell recognition, potentially underlying SARS-CoV-2 serotype-associated T cell immune evasion mechanisms. Our findings reveal the pivotal role of population T cell immune barrier against emerging SARS-CoV-2 variants in a serotype-associated pattern and provide insights into the T cell-oriented universal vaccine development for coronaviruses.
自2019年底出现以来，严重急性呼吸综合征冠状病毒-2 （SARS-CoV-2）通过不断产生具有迭代免疫逃逸能力的变体，不断威胁着人类健康。虽然SARS-CoV-2变体最近根据交叉反应性抗体反应分为六种血清型，但针对这些血清型的T细胞反应特征在很大程度上仍然未知。我们评估了三种不同菌株（原型株，BA.5.2/BF）感染的恢复期SARS-CoV-2刺突特异性T细胞反应。7和XBB/EG.5.1)针对SARS-CoV-2原型和涵盖所有六种血清型的15个亚变体。一般来说，交叉反应T细胞可以识别相同血清型的变异，但它们对后续血清型的变异的反应也较弱。血清I型（原型）恢复者对Omicron变体（血清II至血清IV）的T细胞应答较低，不同血清型菌株之间存在交叉反应的T细胞缺口，即血清II型> III > IV.血清IV型（BA.5.2/BF.7）恢复者对血清V型（XBB/XBB.1.5/XBB.1.16/EG.5.1）菌株的T细胞应答较弱，对血清VI型（BA.2.86/ j .1）菌株的T细胞应答更低。同样，血清型V （XBB）恢复期患者对血清型VI （BA.2.86）株的交叉t细胞反应明显弱于血清型V株。我们还发现了T细胞表位热点区域的关键血清型特征突变，这些突变可能减弱CD8+和/或CD4+ T细胞识别，可能是SARS-CoV-2血清型相关T细胞免疫逃避机制的基础。我们的研究结果揭示了群体T细胞免疫屏障以血清型相关模式对抗新出现的SARS-CoV-2变体的关键作用，并为T细胞导向的冠状病毒通用疫苗开发提供了见解。
{"title":"Broad cross-T cell immunity between emerging SARS-CoV-2 serotypes waved by spike-signature mutations.","authors":"Yuanyuan Guo,Jinmin Tian,Peipei Guo,Xin Wang,Bingli Shang,Junying She,Mengjie Yang,George F Gao,Jun Liu","doi":"10.1080/22221751.2025.2610856","DOIUrl":"https://doi.org/10.1080/22221751.2025.2610856","url":null,"abstract":"Since its emergence in late 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has continuously threatened human health through constantly arising variants with iterative immune escape abilities. While SARS-CoV-2 variants have been recently classified into six serotypes based on cross-reactive antibody responses, T cell response features against these serotypes remain largely unknown. We evaluated SARS-CoV-2 spike-specific T cell responses among convalescents infected by three different strains (prototype, BA.5.2/BF.7, and XBB/EG.5.1) against SARS-CoV-2 prototype and 15 subvariants covering all six serotypes. Generally, cross-reactive T cells could recognize variants within the same serotype, but they also mounted weaker responses to variants from subsequent serotypes. Serotype I (prototype) convalescents showed lower T cell responses against Omicron variants (Serotype II to IV), with cross-reactive T cell gaps between different serotype strains, i.e. Serotype II > III > IV. Serotype IV (BA.5.2/BF.7) convalescents exhibited weaker T cell responses to Serotype V (XBB/XBB.1.5/XBB.1.16/EG.5.1) strains and even lower responses to Serotype VI (BA.2.86/JN.1) strains. Similarly, Serotype V (XBB) convalescents showed significantly weaker cross-T cell responses to the Serotype VI (BA.2.86) strains than to the Serotype V strains. We also identified key serotype-signature mutations in T cell epitope hotspot regions that could attenuate CD8+ and/or CD4+ T cell recognition, potentially underlying SARS-CoV-2 serotype-associated T cell immune evasion mechanisms. Our findings reveal the pivotal role of population T cell immune barrier against emerging SARS-CoV-2 variants in a serotype-associated pattern and provide insights into the T cell-oriented universal vaccine development for coronaviruses.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"6 1","pages":"2610856"},"PeriodicalIF":13.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Congenital babesiosis is rarely reported globally. We report a 74-day-old male infant presented with fever, pallor, and severe, life-threatening haemolytic anaemia (haemoglobin: 45 g/L). The infant had 16% parasitemia with ring forms evident on peripheral blood smear. Babesia microti infection was confirmed in both the mother and infant by PCR and metagenomic next- generation sequencing. Genetic analysis revealed an identical strain in bot. Treatment with intravenous azithromycin and oral atovaquone/proguanil resulted in rapid clearance of parasitemia and resolution of anaemia. This first molecularly confirmed case of congenital B. microti transmission in China demonstrates vertical transmission from an asymptomatic mother. It underscores the need for heightened clinical suspicion in neonates with unexplained haemolytic anaemia in endemic regions and highlights critical gaps in access to essential anti-babesia therapies.
{"title":"Congenital babesiosis in China: first molecularly confirmed case of vertical transmission of Babesia microti.","authors":"Junwen Liu,Dongfang Li,Sen Wang,Shuai Gao,Bin Xu,Junlong Zhao,Qin Liu,Muxin Chen,Xiaonong Zhou,Yuchun Cai,Lan He","doi":"10.1080/22221751.2025.2608389","DOIUrl":"https://doi.org/10.1080/22221751.2025.2608389","url":null,"abstract":"Congenital babesiosis is rarely reported globally. We report a 74-day-old male infant presented with fever, pallor, and severe, life-threatening haemolytic anaemia (haemoglobin: 45 g/L). The infant had 16% parasitemia with ring forms evident on peripheral blood smear. Babesia microti infection was confirmed in both the mother and infant by PCR and metagenomic next- generation sequencing. Genetic analysis revealed an identical strain in bot. Treatment with intravenous azithromycin and oral atovaquone/proguanil resulted in rapid clearance of parasitemia and resolution of anaemia. This first molecularly confirmed case of congenital B. microti transmission in China demonstrates vertical transmission from an asymptomatic mother. It underscores the need for heightened clinical suspicion in neonates with unexplained haemolytic anaemia in endemic regions and highlights critical gaps in access to essential anti-babesia therapies.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"87 1","pages":"2608389"},"PeriodicalIF":13.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1080/22221751.2026.2614742
Xinyue Zhu,Yuyi Tang,Karen Spruyt,Janne Estill,Ivan D Florez,Yasser Sami Amer,Akihiko Ozaki,Yaolong Chen,Enmei Liu
The global molecular epidemiology of Mycoplasma pneumoniae (MP) and its associations with macrolide resistance and disease severity remain unclear. Studies reporting MP genotypes distribution by P1 typing, multiple locus variable number tandem repeat analysis (MLVA), or multilocus sequence typing analysis (MLST) among MP-infected patients were included. Data quality was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa scale. Random-effects models were used to calculate pooled proportions of each MP genotype, with subgroup analyses by geographic region, age group, sex, time period, specimen type, and test assay. The proportions of macrolide-resistant MP and severe MP pneumonia cases were also evaluated. A total of 116 studies met the criteria. Predominant genotypes were P1-1 by P1 typing and 4572 by MLVA in the Western Pacific region and European region, and ST3 by MLST in the Western Pacific region. The proportions of P1-1 and 4572 were higher in the Western Pacific region than in other regions, and in children than in adults, whereas P1-2 and 3562 were opposite. Genotype dominance cycled between P1-1 and P1-2, and between 4572 and 3662. Macrolide resistance rates were highest in P1-1, 4572, and ST3 genotypes. Based on the currently available data, no association was detected between P1 genotypes and disease severity, although the limited sample size restricted the statistical power of this analysis. This comprehensive analysis elucidates the global molecular epidemiology of MP, highlights its clinical implications, and underscores the need for ongoing molecular surveillance to guide management and control strategies.
{"title":"Global molecular epidemiology of Mycoplasma pneumoniae and its association with macrolide resistance and disease severity: a systematic review and meta-analysis.","authors":"Xinyue Zhu,Yuyi Tang,Karen Spruyt,Janne Estill,Ivan D Florez,Yasser Sami Amer,Akihiko Ozaki,Yaolong Chen,Enmei Liu","doi":"10.1080/22221751.2026.2614742","DOIUrl":"https://doi.org/10.1080/22221751.2026.2614742","url":null,"abstract":"The global molecular epidemiology of Mycoplasma pneumoniae (MP) and its associations with macrolide resistance and disease severity remain unclear. Studies reporting MP genotypes distribution by P1 typing, multiple locus variable number tandem repeat analysis (MLVA), or multilocus sequence typing analysis (MLST) among MP-infected patients were included. Data quality was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa scale. Random-effects models were used to calculate pooled proportions of each MP genotype, with subgroup analyses by geographic region, age group, sex, time period, specimen type, and test assay. The proportions of macrolide-resistant MP and severe MP pneumonia cases were also evaluated. A total of 116 studies met the criteria. Predominant genotypes were P1-1 by P1 typing and 4572 by MLVA in the Western Pacific region and European region, and ST3 by MLST in the Western Pacific region. The proportions of P1-1 and 4572 were higher in the Western Pacific region than in other regions, and in children than in adults, whereas P1-2 and 3562 were opposite. Genotype dominance cycled between P1-1 and P1-2, and between 4572 and 3662. Macrolide resistance rates were highest in P1-1, 4572, and ST3 genotypes. Based on the currently available data, no association was detected between P1 genotypes and disease severity, although the limited sample size restricted the statistical power of this analysis. This comprehensive analysis elucidates the global molecular epidemiology of MP, highlights its clinical implications, and underscores the need for ongoing molecular surveillance to guide management and control strategies.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"39 1","pages":"2614742"},"PeriodicalIF":13.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVESTo assess the diagnostic utility of Myxovirus resistance protein A (MxA) in differentiating between viral and non-viral respiratory infections in adults.METHODSThis prospective, multicenter diagnostic accuracy study enrolled adults with acute respiratory infections (ARI) from outpatient and inpatient settings, alongside asymptomatic controls. Peripheral blood was collected for quantitative MxA measurement. Pathogen detection used targeted next-generation sequencing combined with conventional microbiological testing. Aetiological diagnoses were determined using standardized algorithms based on detected pathogens. The diagnostic accuracy of MxA for identifying viral ARIs was calculated.RESULTSAmong 518 ARI patients, 325 had viral pathogens detected, 131 had bacterial/fungal pathogens, and 62 had no pathogen detected. Median MxA levels were significantly higher in viral (123.6 ng/ml; interquartile range [IQR], 56.4-189.6) than bacterial/fungal infections (15.9 ng/ml; IQR, 9.9-38.1; Bonferroni test p < 0.001) and controls (n = 158; 8.2 ng/mL; IQR, <5.0-16.4; Bonferroni test p < .001). The area under the receiver operating characteristic curve (AUC) for differentiating viral from bacterial/fungal infections was 0.83 (95% confidence interval [CI], 0.79-0.87). At an optimal cutoff of 50 ng/ml, MxA yielded a sensitivity of 77.8% (95% CI, 73.3-82.4%) and a specificity of 80.2% (95% CI, 73.3-87.0%). MxA levels were also elevated in atypical bacterial infections (n = 22; 60.9 ng/mL; IQR, 23.4-114.8), with no significant difference from viral group (Bonferroni test p = 0.12). When atypical bacteria were excluded, the AUC for differentiating viral from non-viral infections was 0.80 (95% CI, 0.76-0.84).CONCLUSIONSMxA demonstrates high diagnostic accuracy in distinguishing between viral and non-viral respiratory infections in adults.
{"title":"Myxovirus resistance protein A to differentiate between viral and non-viral respiratory infections in adults: a prospective study.","authors":"Mengwei Yan,Nengyong Wang,Liping Yang,Xiaoqi Zhang,Yong Zhang,Weixia Xuan,Xiaoju Zhang,Gang Liu,Herong Wang,Yao Qing,Yeming Wang,Bin Cao","doi":"10.1080/22221751.2026.2614734","DOIUrl":"https://doi.org/10.1080/22221751.2026.2614734","url":null,"abstract":"OBJECTIVESTo assess the diagnostic utility of Myxovirus resistance protein A (MxA) in differentiating between viral and non-viral respiratory infections in adults.METHODSThis prospective, multicenter diagnostic accuracy study enrolled adults with acute respiratory infections (ARI) from outpatient and inpatient settings, alongside asymptomatic controls. Peripheral blood was collected for quantitative MxA measurement. Pathogen detection used targeted next-generation sequencing combined with conventional microbiological testing. Aetiological diagnoses were determined using standardized algorithms based on detected pathogens. The diagnostic accuracy of MxA for identifying viral ARIs was calculated.RESULTSAmong 518 ARI patients, 325 had viral pathogens detected, 131 had bacterial/fungal pathogens, and 62 had no pathogen detected. Median MxA levels were significantly higher in viral (123.6 ng/ml; interquartile range [IQR], 56.4-189.6) than bacterial/fungal infections (15.9 ng/ml; IQR, 9.9-38.1; Bonferroni test p < 0.001) and controls (n = 158; 8.2 ng/mL; IQR, <5.0-16.4; Bonferroni test p < .001). The area under the receiver operating characteristic curve (AUC) for differentiating viral from bacterial/fungal infections was 0.83 (95% confidence interval [CI], 0.79-0.87). At an optimal cutoff of 50 ng/ml, MxA yielded a sensitivity of 77.8% (95% CI, 73.3-82.4%) and a specificity of 80.2% (95% CI, 73.3-87.0%). MxA levels were also elevated in atypical bacterial infections (n = 22; 60.9 ng/mL; IQR, 23.4-114.8), with no significant difference from viral group (Bonferroni test p = 0.12). When atypical bacteria were excluded, the AUC for differentiating viral from non-viral infections was 0.80 (95% CI, 0.76-0.84).CONCLUSIONSMxA demonstrates high diagnostic accuracy in distinguishing between viral and non-viral respiratory infections in adults.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"83 1","pages":"2614734"},"PeriodicalIF":13.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1080/22221751.2025.2611479
Konrad Wesselmann,Léa Luciani,Gregory Moureau,Jean-Selim Driouich,Ornellie Bernadin,Magali Gilles,Xavier de Lamballerie,Antoine Nougairède
The laboratory mouse (Mus musculus) is the most widely used animal model for preclinical research, with numerous wild-type and genetically modified mouse strains available. Chikungunya virus (CHIKV), a mosquito-borne arthritogenic alphavirus, has emerged in various new regions and caused several millions of cases within the last decade. Mayaro virus (MAYV), an arthritogenic alphaviruses closely related to CHIKV, remains geographically restricted to the Americas. Existing mouse models rely on immunodeficient mice, leading to lethal illness, or footpad injection, which induces localized arthropathy. We present a proof-of-concept study demonstrating how disease severity in mice can be modulated using sub-neutralizing concentrations of an interferon 1 receptor (IFNAR1) blocking monoclonal antibody (mAb). C57BL/6 mice were injected intraperitoneally with varying anti-IFNAR1 antibody doses before intraperitoneal infection with CHIKV or MAYV. For both, CHIKV and MAYV, we observed an anti-IFNAR1 mAb dose-dependent increase in blood viral loads and disease severity. A 1mg dose induced severe disease, whereas a 0.1 mg dose resulted in moderate symptoms in mice, mainly facial pain expression signs, accompanied by detectable viremia in the days preceding symptom onset. Viral loads in organs and serum concentrations of inflammatory cytokines and chemokines were also elevated in mice receiving 0.1mg anti-IFNAR1 mAb. In conclusion, we provide proof of concept that CHIKV and MAYV disease severity can be modulated using low concentrations of anti-IFNAR1 mAb. We used this approach to develop a new infection model for mild systemic disease, based on an accessible strain and a commercial antibody allowing for easy implementation and adaptation.
{"title":"Modulating Chikungunya and Mayaro virus-induced disease severity in mice using low concentrations of anti-IFNAR1 antibodies.","authors":"Konrad Wesselmann,Léa Luciani,Gregory Moureau,Jean-Selim Driouich,Ornellie Bernadin,Magali Gilles,Xavier de Lamballerie,Antoine Nougairède","doi":"10.1080/22221751.2025.2611479","DOIUrl":"https://doi.org/10.1080/22221751.2025.2611479","url":null,"abstract":"The laboratory mouse (Mus musculus) is the most widely used animal model for preclinical research, with numerous wild-type and genetically modified mouse strains available. Chikungunya virus (CHIKV), a mosquito-borne arthritogenic alphavirus, has emerged in various new regions and caused several millions of cases within the last decade. Mayaro virus (MAYV), an arthritogenic alphaviruses closely related to CHIKV, remains geographically restricted to the Americas. Existing mouse models rely on immunodeficient mice, leading to lethal illness, or footpad injection, which induces localized arthropathy. We present a proof-of-concept study demonstrating how disease severity in mice can be modulated using sub-neutralizing concentrations of an interferon 1 receptor (IFNAR1) blocking monoclonal antibody (mAb). C57BL/6 mice were injected intraperitoneally with varying anti-IFNAR1 antibody doses before intraperitoneal infection with CHIKV or MAYV. For both, CHIKV and MAYV, we observed an anti-IFNAR1 mAb dose-dependent increase in blood viral loads and disease severity. A 1mg dose induced severe disease, whereas a 0.1 mg dose resulted in moderate symptoms in mice, mainly facial pain expression signs, accompanied by detectable viremia in the days preceding symptom onset. Viral loads in organs and serum concentrations of inflammatory cytokines and chemokines were also elevated in mice receiving 0.1mg anti-IFNAR1 mAb. In conclusion, we provide proof of concept that CHIKV and MAYV disease severity can be modulated using low concentrations of anti-IFNAR1 mAb. We used this approach to develop a new infection model for mild systemic disease, based on an accessible strain and a commercial antibody allowing for easy implementation and adaptation.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"56 1","pages":"2611479"},"PeriodicalIF":13.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1080/22221751.2026.2616946
Amy E Davis,Yin Su,Ronald Dallas,Pamela Freiden,Janet A Englund,Eileen J Klein,Hana Hakim,Randall Hayden,Gabriela Maron,Elisa Margolis,Li Tang,Valerie Cortez,Stacey Schultz-Cherry
Human astroviruses are a common cause of viral gastroenteritis and are often underdiagnosed. While infections are typically mild or asymptomatic in immunocompetent hosts, astrovirus can cause prolonged and severe disease in immunocompromised individuals. Here, we conducted a case-control study to evaluate the clinical presentation of astrovirus infections in pediatric oncology patients. Our findings were compared to two groups: (1) norovirus infections in the same immunocompromised cohort, and (2) a cohort of immunocompetent children with and without diarrheal symptoms. Astrovirus was detected in 9.8% of immunocompromised patients, with prolonged shedding seen in multiple cases. Astrovirus infection was associated with an increased odds of diarrhea, although this association weakened when adjusting for co-infections. In contrast, norovirus was not significantly associated with diarrhea in immunocompromised patients, despite prolonged shedding in 24% of the cohort. High rates of co-infection with adenovirus and Clostridium difficile may have influenced symptom patterns. In the immunocompetent cohort, astrovirus was not associated with diarrhea, while norovirus showed a strong association with symptoms. These findings indicate that astrovirus infections are more likely to cause diarrhea in immunocompromised pediatric patients, while often asymptomatic in immunocompetent children. Norovirus showed the opposite trend, highlighting distinct roles of host immune status in shaping clinical outcomes. These findings highlight the importance of considering astrovirus as a potential contributor to gastrointestinal symptoms in immunocompromised children and call for broader diagnostic testing and further research on viral co-infections and persistence.
{"title":"Astrovirus and norovirus infections and their association with diarrheal symptoms in immunocompromised children.","authors":"Amy E Davis,Yin Su,Ronald Dallas,Pamela Freiden,Janet A Englund,Eileen J Klein,Hana Hakim,Randall Hayden,Gabriela Maron,Elisa Margolis,Li Tang,Valerie Cortez,Stacey Schultz-Cherry","doi":"10.1080/22221751.2026.2616946","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616946","url":null,"abstract":"Human astroviruses are a common cause of viral gastroenteritis and are often underdiagnosed. While infections are typically mild or asymptomatic in immunocompetent hosts, astrovirus can cause prolonged and severe disease in immunocompromised individuals. Here, we conducted a case-control study to evaluate the clinical presentation of astrovirus infections in pediatric oncology patients. Our findings were compared to two groups: (1) norovirus infections in the same immunocompromised cohort, and (2) a cohort of immunocompetent children with and without diarrheal symptoms. Astrovirus was detected in 9.8% of immunocompromised patients, with prolonged shedding seen in multiple cases. Astrovirus infection was associated with an increased odds of diarrhea, although this association weakened when adjusting for co-infections. In contrast, norovirus was not significantly associated with diarrhea in immunocompromised patients, despite prolonged shedding in 24% of the cohort. High rates of co-infection with adenovirus and Clostridium difficile may have influenced symptom patterns. In the immunocompetent cohort, astrovirus was not associated with diarrhea, while norovirus showed a strong association with symptoms. These findings indicate that astrovirus infections are more likely to cause diarrhea in immunocompromised pediatric patients, while often asymptomatic in immunocompetent children. Norovirus showed the opposite trend, highlighting distinct roles of host immune status in shaping clinical outcomes. These findings highlight the importance of considering astrovirus as a potential contributor to gastrointestinal symptoms in immunocompromised children and call for broader diagnostic testing and further research on viral co-infections and persistence.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"10 1","pages":"2616946"},"PeriodicalIF":13.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1080/22221751.2026.2616945
Gabriela S Prates,Xiaoyi Li,Victor Folgosi,Ciniso S Shabangu,George G Souza,Carlos Apoliano,Maria R Gascon,Mariana A Monteiro,Carolina Gualqui,Rosangela Santos Eichler,Helio Gomes,Nikesh Katuwal,Cassandra Gilbert,Yuyang Tang,Jorge Casseb,Guochun Jiang
Despite effective antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) persist in people with HIV (PWH). The central nervous system (CNS) may act as a viral reservoir due to limited ART penetration and virological discordance between plasma and cerebrospinal fluid (CSF). In a cross-sectional study of 24 ART-treated PWH, participants were stratified as cognitively normal (CN, n = 10) or HAND (n = 14), including asymptomatic neurocognitive impairment (ANI, n = 3), mild neurocognitive disorder (MND, n = 9), and HIV-associated dementia (HAD, n = 2). HIV RNA was quantified in paired plasma and CSF by RT-ddPCR. CSF peptidome profiling was performed using mass spectrometry, and ART concentrations were measured by LC-MS/MS. HIV infectivity in CSF was assessed via viral outgrowth assays. HIV RNA was undetectable in plasma but present in CSF from HAND participants, indicating compartmentalized viral persistence. Tenofovir and lamivudine levels were higher in plasma, whereas dolutegravir trended higher in CSF. Nevertheless, all CSF drug concentrations exceeded their IC50 values in effectively suppressing active HIV replication. Peptidomic analysis identified HIV-derived peptides (e.g., Env and Pol) exclusively in HAND samples, accompanied by an early reduction in β-tau. Although HIV RNA and peptides were detectable, no productive infection was established by CSF in permissive immune cells. Together, despite pharmacologically sufficient ART penetration, HIV persists in the CSF of PWH with HAND. These findings suggest that the latent HIV infection with non-replicative viral expression, rather than residual active HIV replication, may contribute to neuroinflammation and cognitive decline in PWH on suppressive ART.
尽管抗逆转录病毒治疗（ART）有效，HIV相关神经认知障碍（HAND）在HIV感染者（PWH）中持续存在。中枢神经系统（CNS）可能作为病毒库，由于有限的抗逆转录病毒药物渗透和血浆和脑脊液（CSF）之间的病毒学不一致。在一项针对24例接受art治疗的PWH患者的横断面研究中，参与者被分为认知正常（CN, n = 10）或HAND (n = 14)，包括无症状神经认知障碍（ANI, n = 3）、轻度神经认知障碍（MND, n = 9）和hiv相关痴呆（HAD, n = 2）。采用RT-ddPCR定量检测配对血浆和脑脊液中的HIV RNA。采用质谱法进行脑脊液肽肽谱分析，采用LC-MS/MS法测定ART浓度。通过病毒生长试验评估脑脊液中HIV的感染性。HIV RNA在血浆中检测不到，但在HAND参与者的CSF中存在，表明病毒存在区隔性。替诺福韦和拉米夫定在血浆中的水平较高，而多替替韦在脑脊液中的水平趋于较高。然而，所有CSF药物浓度均超过其IC50值，有效抑制活跃的HIV复制。肽组学分析发现hiv衍生肽（例如，Env和Pol）仅在HAND样品中，伴随着β-tau的早期减少。虽然检测到HIV RNA和多肽，但CSF在允许免疫细胞中未建立生产性感染。总之，尽管抗逆转录病毒药物在药理学上有足够的渗透，但HIV仍然存在于患有HAND的PWH CSF中。这些发现表明，具有非复制性病毒表达的潜伏性HIV感染，而不是残留的活性HIV复制，可能导致PWH在抑制性抗逆转录病毒治疗中出现神经炎症和认知能力下降。
{"title":"HIV expression persists in the cerebrospinal fluid of HIV-associated neurocognitive disorders despite effective ART.","authors":"Gabriela S Prates,Xiaoyi Li,Victor Folgosi,Ciniso S Shabangu,George G Souza,Carlos Apoliano,Maria R Gascon,Mariana A Monteiro,Carolina Gualqui,Rosangela Santos Eichler,Helio Gomes,Nikesh Katuwal,Cassandra Gilbert,Yuyang Tang,Jorge Casseb,Guochun Jiang","doi":"10.1080/22221751.2026.2616945","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616945","url":null,"abstract":"Despite effective antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) persist in people with HIV (PWH). The central nervous system (CNS) may act as a viral reservoir due to limited ART penetration and virological discordance between plasma and cerebrospinal fluid (CSF). In a cross-sectional study of 24 ART-treated PWH, participants were stratified as cognitively normal (CN, n = 10) or HAND (n = 14), including asymptomatic neurocognitive impairment (ANI, n = 3), mild neurocognitive disorder (MND, n = 9), and HIV-associated dementia (HAD, n = 2). HIV RNA was quantified in paired plasma and CSF by RT-ddPCR. CSF peptidome profiling was performed using mass spectrometry, and ART concentrations were measured by LC-MS/MS. HIV infectivity in CSF was assessed via viral outgrowth assays. HIV RNA was undetectable in plasma but present in CSF from HAND participants, indicating compartmentalized viral persistence. Tenofovir and lamivudine levels were higher in plasma, whereas dolutegravir trended higher in CSF. Nevertheless, all CSF drug concentrations exceeded their IC50 values in effectively suppressing active HIV replication. Peptidomic analysis identified HIV-derived peptides (e.g., Env and Pol) exclusively in HAND samples, accompanied by an early reduction in β-tau. Although HIV RNA and peptides were detectable, no productive infection was established by CSF in permissive immune cells. Together, despite pharmacologically sufficient ART penetration, HIV persists in the CSF of PWH with HAND. These findings suggest that the latent HIV infection with non-replicative viral expression, rather than residual active HIV replication, may contribute to neuroinflammation and cognitive decline in PWH on suppressive ART.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"27 1","pages":"2616945"},"PeriodicalIF":13.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Listeriosis is a severe foodborne infection and associated with high mortality. Treatment is based on ampicillin, amoxicillin or penicillin, often combined with gentamicin, but meropenem is also used occasionally. β-lactam resistant Listeria monocytogenes isolates are infrequently described but the mechanism of resistance is not known. A clinical L. monocytogenes isolate with reduced β-lactam susceptibility was collected from a German listeriosis patient. Resistance profiling, whole genome sequencing, comparative genomics and genetic experiments were used to identify the causative DNA polymorphism. A W428R substitution near the active site of penicillin binding protein B1 (PBPB1) was identified as the cause of reduced ampicillin, amoxicillin and meropenem susceptibility. Further clinical L. monocytogenes isolates with similar susceptibility profiles were found by searching the genome database of the German consultant laboratory for Listeria for pbpB1 W428R-positive isolates. Spontaneous suppressors of L. monocytogenes reference strain EGD-e with reduced β-lactam susceptibility were selected during ampicillin exposure and their genomes were sequenced. The same pbpB1 mutation emerged in strain EGD-e during cultivation in the presence of ampicillin. Further experiments showed that meropenem also promotes the development of resistant suppressor mutants with pbpB1 mutations. Our work demonstrates that β-lactam susceptibility of L. monocytogenes can be reduced through a specific substitution in PBPB1. This mutation is potentially selected for during β-lactam treatment.
{"title":"A pbpB1 mutation causing reduced β-lactam susceptibility in clinical Listeria monocytogenes isolates.","authors":"Sabrina Wamp,Rosalyn Wagner,Franziska Schuler,Alexander Krüttgen,Antje Flieger,Sven Halbedel","doi":"10.1080/22221751.2026.2616949","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616949","url":null,"abstract":"Listeriosis is a severe foodborne infection and associated with high mortality. Treatment is based on ampicillin, amoxicillin or penicillin, often combined with gentamicin, but meropenem is also used occasionally. β-lactam resistant Listeria monocytogenes isolates are infrequently described but the mechanism of resistance is not known. A clinical L. monocytogenes isolate with reduced β-lactam susceptibility was collected from a German listeriosis patient. Resistance profiling, whole genome sequencing, comparative genomics and genetic experiments were used to identify the causative DNA polymorphism. A W428R substitution near the active site of penicillin binding protein B1 (PBPB1) was identified as the cause of reduced ampicillin, amoxicillin and meropenem susceptibility. Further clinical L. monocytogenes isolates with similar susceptibility profiles were found by searching the genome database of the German consultant laboratory for Listeria for pbpB1 W428R-positive isolates. Spontaneous suppressors of L. monocytogenes reference strain EGD-e with reduced β-lactam susceptibility were selected during ampicillin exposure and their genomes were sequenced. The same pbpB1 mutation emerged in strain EGD-e during cultivation in the presence of ampicillin. Further experiments showed that meropenem also promotes the development of resistant suppressor mutants with pbpB1 mutations. Our work demonstrates that β-lactam susceptibility of L. monocytogenes can be reduced through a specific substitution in PBPB1. This mutation is potentially selected for during β-lactam treatment.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"45 1","pages":"2616949"},"PeriodicalIF":13.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Active case-finding (ACF) strategies for tuberculosis (TB) in high-incidence rural areas require cost-effective solutions. We evaluated a novel community-based ACF strategy integrating pooled sputum molecular testing via Xpert® MTB/RIF Ultra. A prospective study was conducted in three high-TB-incidence rural townships in Zhejiang, China (2024). Residents aged ≥65 years underwent centralized health check-ups, including chest X-rays (CXR). Sputum samples from eight consecutive individuals with abnormal CXR findings were pooled for Xpert® MTB/RIF Ultra testing. Positive pools prompted individual retesting. Participants with positive individual test results were referred to designated hospitals for standardized treatment. Among 16,558 eligible residents, 6,960 (42.0%) participated. CXR abnormalities were detected in 1,912 participants (27.5%), with 1,883 providing sputum samples. Pooled testing identified 32 bacteriologically confirmed TB cases among 1,883 participants with CXR abnormalities, yielding a detection rate of 1.7%. The number needed to screen (NNS) to identify one case was 218, which was 177 fewer than that required by the chest X-ray-based alone active case finding strategy. Screening yields of newly detected TB through ACF was 0.460%. The innovative strategy reduced per-case screening costs to US$4.37 (vs. US$54.78 for individual testing) and per-confirmed-case cost to US$949.49. Integrating a pooled Xpert® MTB/RIF Ultra testing with routine health check-ups provides a high-yield, cost-effective ACF strategy for detecting active TB in high-risk elderly populations in rural settings. This approach addresses key barriers to scalable community-based screening.
{"title":"Community-based \"X-ray+Xpert® MTB/RIF ultra pooling test\" case-finding strategy among high-risk groups in rural areas: a prospective application study.","authors":"Zhengwei Liu,Ruiqi Chen,Bing Li,Junhang Pan,Bowen Xie,Qi Wu,Xinghui Gao,Mingwu Zhang,Yelei Zhu,Kunyang Wu,Haiting Chen,David H Persing,Yi-Wei Tang,Bin Chen,Qingrong Zhou,Jianmin Jiang","doi":"10.1080/22221751.2025.2610857","DOIUrl":"https://doi.org/10.1080/22221751.2025.2610857","url":null,"abstract":"Active case-finding (ACF) strategies for tuberculosis (TB) in high-incidence rural areas require cost-effective solutions. We evaluated a novel community-based ACF strategy integrating pooled sputum molecular testing via Xpert® MTB/RIF Ultra. A prospective study was conducted in three high-TB-incidence rural townships in Zhejiang, China (2024). Residents aged ≥65 years underwent centralized health check-ups, including chest X-rays (CXR). Sputum samples from eight consecutive individuals with abnormal CXR findings were pooled for Xpert® MTB/RIF Ultra testing. Positive pools prompted individual retesting. Participants with positive individual test results were referred to designated hospitals for standardized treatment. Among 16,558 eligible residents, 6,960 (42.0%) participated. CXR abnormalities were detected in 1,912 participants (27.5%), with 1,883 providing sputum samples. Pooled testing identified 32 bacteriologically confirmed TB cases among 1,883 participants with CXR abnormalities, yielding a detection rate of 1.7%. The number needed to screen (NNS) to identify one case was 218, which was 177 fewer than that required by the chest X-ray-based alone active case finding strategy. Screening yields of newly detected TB through ACF was 0.460%. The innovative strategy reduced per-case screening costs to US$4.37 (vs. US$54.78 for individual testing) and per-confirmed-case cost to US$949.49. Integrating a pooled Xpert® MTB/RIF Ultra testing with routine health check-ups provides a high-yield, cost-effective ACF strategy for detecting active TB in high-risk elderly populations in rural settings. This approach addresses key barriers to scalable community-based screening.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"34 1","pages":"2610857"},"PeriodicalIF":13.2,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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