Pub Date : 2025-12-30DOI: 10.1016/j.jinf.2025.106671
Leran He , Siyu Chen , Qinghong Meng, Dan Yu, Kaihu Yao
{"title":"The rapid decline in cases argues against improved surveillance as the main cause of 2024 pertussis outbreak in China","authors":"Leran He , Siyu Chen , Qinghong Meng, Dan Yu, Kaihu Yao","doi":"10.1016/j.jinf.2025.106671","DOIUrl":"10.1016/j.jinf.2025.106671","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 2","pages":"Article 106671"},"PeriodicalIF":11.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1016/j.jinf.2025.106672
Tomasz Wybranowski, Marta Napiórkowska-Mastalerz, Kamila Dybowska, Ewa Żekanowska, Stefan Kruszewski, Grzegorz Przybylski
{"title":"Butyrylcholinesterase as an overlooked prognostic biomarker of 100-day mortality in non-COVID CAP","authors":"Tomasz Wybranowski, Marta Napiórkowska-Mastalerz, Kamila Dybowska, Ewa Żekanowska, Stefan Kruszewski, Grzegorz Przybylski","doi":"10.1016/j.jinf.2025.106672","DOIUrl":"10.1016/j.jinf.2025.106672","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 2","pages":"Article 106672"},"PeriodicalIF":11.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.jinf.2025.106669
Thi Cam Tu Ha , Sheila Orwa , Sandra Guedes , Kelle Moley , Kristin Wannerberger , Anders Elfvin , Martin J. Blaser , Unnur Gudnadottir , Nele Brusselaers
Objectives
To examine the association between prenatal antibiotic exposure and Group B Streptococcus (GBS) disease within 4 weeks postpartum.
Methods
We conducted a population-based cohort study including all singleton live births in Sweden from 2006 to 2016, using national registers. Neonates were classified by prenatal antibiotic exposure status, and GBS disease was ascertained within four weeks postpartum. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression with a robust variance estimator. Effect heterogeneity by GBS risk factors was evaluated, and potential confounding by indication was assessed by additional adjustment for these risk factors.
Results
Among 1,095,644 liveborn singletons, 24.5% were exposed to antibiotics. GBS incidence was higher among exposed neonates than unexposed (0.86 vs. 0.66 per 1000 live births; aOR, 1.29; 95% CI, 1.10–1.50), particularly among neonates without GBS risk factors (aOR, 1.34; 95% CI, 1.12–1.60). The strongest association occurred with early third-trimester exposure (aOR, 1.67; 95% CI, 1.17–2.38). Associations for antibiotics given within four weeks of delivery attenuated after adjustment for GBS risk factors.
Conclusions
Prenatal antibiotic exposure can raise GBS risk within 4 weeks postpartum, especially in neonates not covered by risk-based intrapartum prophylaxis, with the early third-trimester being a critical window of susceptibility.
{"title":"Antibiotic use during pregnancy and neonatal Group B Streptococcus disease","authors":"Thi Cam Tu Ha , Sheila Orwa , Sandra Guedes , Kelle Moley , Kristin Wannerberger , Anders Elfvin , Martin J. Blaser , Unnur Gudnadottir , Nele Brusselaers","doi":"10.1016/j.jinf.2025.106669","DOIUrl":"10.1016/j.jinf.2025.106669","url":null,"abstract":"<div><h3>Objectives</h3><div>To examine the association between prenatal antibiotic exposure and Group B Streptococcus (GBS) disease within 4 weeks postpartum.</div></div><div><h3>Methods</h3><div>We conducted a population-based cohort study including all singleton live births in Sweden from 2006 to 2016, using national registers. Neonates were classified by prenatal antibiotic exposure status, and GBS disease was ascertained within four weeks postpartum. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression with a robust variance estimator. Effect heterogeneity by GBS risk factors was evaluated, and potential confounding by indication was assessed by additional adjustment for these risk factors.</div></div><div><h3>Results</h3><div>Among 1,095,644 liveborn singletons, 24.5% were exposed to antibiotics. GBS incidence was higher among exposed neonates than unexposed (0.86 vs. 0.66 per 1000 live births; aOR, 1.29; 95% CI, 1.10–1.50), particularly among neonates without GBS risk factors (aOR, 1.34; 95% CI, 1.12–1.60). The strongest association occurred with early third-trimester exposure (aOR, 1.67; 95% CI, 1.17–2.38). Associations for antibiotics given within four weeks of delivery attenuated after adjustment for GBS risk factors.</div></div><div><h3>Conclusions</h3><div>Prenatal antibiotic exposure can raise GBS risk within 4 weeks postpartum, especially in neonates not covered by risk-based intrapartum prophylaxis, with the early third-trimester being a critical window of susceptibility.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 2","pages":"Article 106669"},"PeriodicalIF":11.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on “Tuberculosis incidence in solid organ transplant recipients in Europe: A multicenter TBnet cohort study”","authors":"Kanishka Harariya, Thakur Rohit Singh, Ankita Kalra, Swarupanjali Padhi, Fayaz Ahamed","doi":"10.1016/j.jinf.2025.106670","DOIUrl":"10.1016/j.jinf.2025.106670","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 2","pages":"Article 106670"},"PeriodicalIF":11.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1016/j.jinf.2025.106667
Jianwen Situ , Tsz Chung Wong , Shusheng Wu , Zhiyu Li , Estie Hon Kiu Shun , Siu Fung Stanley Ho , Cyril Chik Yan Yip , Kelvin Hon Yin Lo , James Yiu Hung Tsoi , Weihui Ma , Andrew Tsz King Lo , Jayden Yiu , Esmond Yan Tik Ng , Ming Yeung Kwong , Christina Yuen Ling Ip , Hiu Laam Chung , Nicholas Foo Siong Chew , Yonghao Liang , Weiwei Mao , Xiaodan Ma , Siddharth Sridhar
Objectives
Rocahepevirus ratti genotype 1 (rHEV), commonly known as rat hepatitis E virus, is a recently identified cause of viral hepatitis. We compared rHEV infections with conventional hepatitis E and measured rHEV seroprevalence in a large diverse human serum cohort.
Methods
Patients with hepatitis (n=2018) were tested for rHEV RNA in the context of a real-world clinical service in Hong Kong. rHEV IgG seroprevalence in various risk groups was measured using a validated immunoassay. Commensal rats were tested for rHEV RNA and sequences were compared with human-derived strains.
Results
From 2017 to 2025, 22 human rHEV infections were identified. Of these, 14 (63·6%) were immunocompromised compared to 22/78 (28·2%) conventional HEV patients (p<0.01). Hepatitis was milder in rHEV patients, but most immunocompromised rHEV patients progressed to chronic infection. Rat-derived rHEV belonged to two subtypes, one of which infected humans. Of 8294 individuals, 57 (0·7%) tested positive for rHEV IgG compared to 551 (6·6%) for HEV IgG. Increasing age predicted rHEV seropositivity (OR:1·03; 95% CI:1·01–1·05); persons with bloodborne pathogens did not exhibit higher rHEV seroprevalence.
Conclusions
rHEV is a sporadic cause of hepatitis in humans with disproportionate clinical significance for immunocompromised hosts. Although clearly linked to rat epizootics, routes of rHEV transmission remain enigmatic.
{"title":"Epidemiology and clinical characteristics of rat hepatitis E virus infection in humans","authors":"Jianwen Situ , Tsz Chung Wong , Shusheng Wu , Zhiyu Li , Estie Hon Kiu Shun , Siu Fung Stanley Ho , Cyril Chik Yan Yip , Kelvin Hon Yin Lo , James Yiu Hung Tsoi , Weihui Ma , Andrew Tsz King Lo , Jayden Yiu , Esmond Yan Tik Ng , Ming Yeung Kwong , Christina Yuen Ling Ip , Hiu Laam Chung , Nicholas Foo Siong Chew , Yonghao Liang , Weiwei Mao , Xiaodan Ma , Siddharth Sridhar","doi":"10.1016/j.jinf.2025.106667","DOIUrl":"10.1016/j.jinf.2025.106667","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Rocahepevirus ratti</em> genotype 1 (rHEV), commonly known as rat hepatitis E virus, is a recently identified cause of viral hepatitis. We compared rHEV infections with conventional hepatitis E and measured rHEV seroprevalence in a large diverse human serum cohort.</div></div><div><h3>Methods</h3><div>Patients with hepatitis (n=2018) were tested for rHEV RNA in the context of a real-world clinical service in Hong Kong. rHEV IgG seroprevalence in various risk groups was measured using a validated immunoassay. Commensal rats were tested for rHEV RNA and sequences were compared with human-derived strains.</div></div><div><h3>Results</h3><div>From 2017 to 2025, 22 human rHEV infections were identified. Of these, 14 (63·6%) were immunocompromised compared to 22/78 (28·2%) conventional HEV patients (p<0.01). Hepatitis was milder in rHEV patients, but most immunocompromised rHEV patients progressed to chronic infection. Rat-derived rHEV belonged to two subtypes, one of which infected humans. Of 8294 individuals, 57 (0·7%) tested positive for rHEV IgG compared to 551 (6·6%) for HEV IgG. Increasing age predicted rHEV seropositivity (OR:1·03; 95% CI:1·01–1·05); persons with bloodborne pathogens did not exhibit higher rHEV seroprevalence.</div></div><div><h3>Conclusions</h3><div>rHEV is a sporadic cause of hepatitis in humans with disproportionate clinical significance for immunocompromised hosts. Although clearly linked to rat epizootics, routes of rHEV transmission remain enigmatic.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 1","pages":"Article 106667"},"PeriodicalIF":11.9,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.jinf.2025.106666
Yi-Yu Lyu , Yu-Shan Zhang , Jie-Hao Tai , Jun-Li Yan , Wen Huang , Wen-Wen Chu , Min Yang , Qiang Zhou , Yi-Le Wu
Objectives
A prospective multicenter study was conducted to elucidate the phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae (CRE) colonization and infection strains.
Methods
Strains were collected within one year from ten intensive care units (ICUs) in Anhui Province, China. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed.
Results
Among 310 colonization and 108 infection strains, Klebsiella pneumoniae predominated (74.4%), followed by Escherichia coli (18.4%). Resistance rates were low to tigecycline (2.6%) and colistin (4.2%) and high (>97.9%) to carbapenems, cephalosporins, and β-lactam/β-lactamase inhibitor combinations. Both sequence types (STs) and capsular serotypes showed substantial geographic diversity. ST11 was the predominant ST, while ST15-KL19 (34.4%) was the most frequent combination in colonization and infection strains. Notably, the ST48-KL62 clone was significantly more prevalent in infection strains than in colonization strains. Moreover, 86.6% of strains produced carbapenemases, primarily blaKPC-2 (64.4%), and 1.9% co-produced KPC- and MBL-type enzymes. High-risk E. coli ST167 strains carrying blaNDM-5 were identified. All CRKp carried biosynthetic genes for the siderophore (e.g., fepABCDG, iutA, iroEN). Virulence factors, including iucABCD, irp1/2, ybtAEPQSTUX, and fyuA, were significantly more prevalent in CRKp infection strains. However, ST15-KL19 lacked classic high-virulence factors (e.g., iucABCD, rmpA, rmpA2). Closely related strains were found within and across hospitals, indicating regional spread and intra-hospital transmission.
Conclusions
This study not only characterizes the distinct regional and genomic distribution patterns of CRE but also associates specific clones and virulence determinants with infection risk, thereby providing molecular markers to identify high-risk carriers and facilitate targeted treatment, prevention, and control measures.
{"title":"Phenotypic and genotypic characterization of colonization and infection with carbapenem-resistant Enterobacteriaceae: A prospective cohort study in China","authors":"Yi-Yu Lyu , Yu-Shan Zhang , Jie-Hao Tai , Jun-Li Yan , Wen Huang , Wen-Wen Chu , Min Yang , Qiang Zhou , Yi-Le Wu","doi":"10.1016/j.jinf.2025.106666","DOIUrl":"10.1016/j.jinf.2025.106666","url":null,"abstract":"<div><h3>Objectives</h3><div>A prospective multicenter study was conducted to elucidate the phenotypic and genotypic characteristics of carbapenem-resistant <em>Enterobacteriaceae</em> (CRE) colonization and infection strains.</div></div><div><h3>Methods</h3><div>Strains were collected within one year from ten intensive care units (ICUs) in Anhui Province, China. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed.</div></div><div><h3>Results</h3><div>Among 310 colonization and 108 infection strains, <em>Klebsiella pneumoniae</em> predominated (74.4%), followed by <em>Escherichia coli</em> (18.4%). Resistance rates were low to tigecycline (2.6%) and colistin (4.2%) and high (>97.9%) to carbapenems, cephalosporins, and <em>β</em>-lactam/<em>β-</em>lactamase inhibitor combinations. Both sequence types (STs) and capsular serotypes showed substantial geographic diversity. ST11 was the predominant ST, while ST15-KL19 (34.4%) was the most frequent combination in colonization and infection strains. Notably, the ST48-KL62 clone was significantly more prevalent in infection strains than in colonization strains. Moreover, 86.6% of strains produced carbapenemases, primarily <em>bla</em><sub>KPC-2</sub> (64.4%), and 1.9% co-produced KPC- and MBL-type enzymes. High-risk <em>E. coli</em> ST167 strains carrying <em>bla</em><sub>NDM-5</sub> were identified. All CR<em>Kp</em> carried biosynthetic genes for the siderophore (e.g., <em>fepABCDG</em>, <em>iutA</em>, <em>iroEN</em>). Virulence factors, including <em>iucABCD</em>, <em>irp1/2</em>, <em>ybtAEPQSTUX</em>, and <em>fyuA</em>, were significantly more prevalent in CR<em>Kp</em> infection strains. However, ST15-KL19 lacked classic high-virulence factors (e.g., <em>iucABCD</em>, <em>rmpA</em>, <em>rmpA2</em>). Closely related strains were found within and across hospitals, indicating regional spread and intra-hospital transmission.</div></div><div><h3>Conclusions</h3><div>This study not only characterizes the distinct regional and genomic distribution patterns of CRE but also associates specific clones and virulence determinants with infection risk, thereby providing molecular markers to identify high-risk carriers and facilitate targeted treatment, prevention, and control measures.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 1","pages":"Article 106666"},"PeriodicalIF":11.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1016/j.jinf.2025.106665
Murielle Baltazar , Laura C. Jacques , Teerawit Audshasai , Marie O'Brien , Aras Kadioglu
Objectives
Streptococcus pneumoniae serotype 1 (S1) is a major cause of invasive pneumococcal disease. Despite its high attack rate, S1 exhibits a low carriage prevalence within the population, which raises questions about the relationship between nasopharyngeal carriage and transmission of hypervirulent strains between individuals. We compared the transmission dynamics of S1 to serotypes 2 (S2) and 3 (S3) using a novel model of transmission in adolescent mice.
Methods
Donor “index” mice were intranasally infected with S1, S2, S3 or isogenic pneumolysin-deficient mutants and co-housed with naïve recipient “contact” mice. Three days later, all mice were infected with influenza A virus (IAV). Pneumococcal transmission was analysed during colonisation alone and co-infection with IAV by quantification of the nasal shedding and nasopharyngeal bacterial density in both index and contact mice. The role of the polysaccharide capsule and toxin pneumolysin, as well as biofilm production in shedding and transmission, and the host nasopharyngeal immune response, were investigated.
Results
We show that S1 was shed at significantly greater levels than S2 and S3 in index mice, which led to significantly higher shedding and transmission rates in contact mice. S1 produced less biofilm and a thick capsule that promoted its increased shedding and transmission. Interestingly, pneumococcal acquisition led to pneumolysin-dependant macrophage recruitment in the nasopharynx of contact mice.
Conclusion
Our results show that rapid and high transmission rate of serotype 1 is a key factor for its success in disseminating quickly within the population and causing outbreaks.
{"title":"Hypervirulent serotype 1 pneumococci display high levels of nasal shedding and rapid onward transmission","authors":"Murielle Baltazar , Laura C. Jacques , Teerawit Audshasai , Marie O'Brien , Aras Kadioglu","doi":"10.1016/j.jinf.2025.106665","DOIUrl":"10.1016/j.jinf.2025.106665","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Streptococcus pneumoniae</em> serotype 1 (S1) is a major cause of invasive pneumococcal disease. Despite its high attack rate, S1 exhibits a low carriage prevalence within the population, which raises questions about the relationship between nasopharyngeal carriage and transmission of hypervirulent strains between individuals. We compared the transmission dynamics of S1 to serotypes 2 (S2) and 3 (S3) using a novel model of transmission in adolescent mice.</div></div><div><h3>Methods</h3><div>Donor “index” mice were intranasally infected with S1, S2, S3 or isogenic pneumolysin-deficient mutants and co-housed with naïve recipient “contact” mice. Three days later, all mice were infected with influenza A virus (IAV). Pneumococcal transmission was analysed during colonisation alone and co-infection with IAV by quantification of the nasal shedding and nasopharyngeal bacterial density in both index and contact mice. The role of the polysaccharide capsule and toxin pneumolysin, as well as biofilm production in shedding and transmission, and the host nasopharyngeal immune response, were investigated.</div></div><div><h3>Results</h3><div>We show that S1 was shed at significantly greater levels than S2 and S3 in index mice, which led to significantly higher shedding and transmission rates in contact mice. S1 produced less biofilm and a thick capsule that promoted its increased shedding and transmission. Interestingly, pneumococcal acquisition led to pneumolysin-dependant macrophage recruitment in the nasopharynx of contact mice.</div></div><div><h3>Conclusion</h3><div>Our results show that rapid and high transmission rate of serotype 1 is a key factor for its success in disseminating quickly within the population and causing outbreaks.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 1","pages":"Article 106665"},"PeriodicalIF":11.9,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.jinf.2025.106664
Molin Yue , Sojin Lee , Shiyue Tao , Geizecler Tomazetto , Kristin Yahner , Hui Liu , Matthew C. Lee , Mary Patricia Nowalk , Richard K. Zimmerman , Monika Johnson , William MacDonald , Erick Forno , Wei Chen , Nader Shaikh
Prediction of outcomes of SARS-CoV-2 infection remains challenging, particularly in the early days following exposure. To better understand the heterogeneity of disease progression, we investigated the early immune response in the upper respiratory tract using transcriptomic analysis, comparing individuals who remained asymptomatic to those who developed symptoms of COVID-19. We conducted a study of 74 individuals (43 children, 31 adults) with confirmed SARS-CoV-2 infection. Mid-turbinate nasal swabs were collected during the first few days of infection and again one week later. We performed a paired analysis comparing baseline and follow-up nasal human gene expression. Additionally, we conducted a predictive analysis to identify transcripts associated with the development of symptomatic infection. From the differentially expressed transcripts in both analyses, we developed a predictive model to assess the likelihood of symptomatic disease. We also compared gene expression patterns between children and adults. A robust interferon response in the upper respiratory tract was strongly associated with the development of symptomatic infection. A panel of five interferon-stimulated genes (TAP2, DDX60, IFIT5, APOL6, and IFI6) predicted symptomatic infection with reasonable accuracy (area under the curve = 0.84). Notably, adaptive immune responses, including T-cell activation and cytokine signaling, differed substantially between children and adults. Our findings suggest that early measurement of interferon-stimulated gene expression may help identify individuals at risk of developing symptomatic COVID-19.
{"title":"Upper airway transcriptomics early after SARS-CoV-2 infection to identify individuals likely to develop symptomatic infection","authors":"Molin Yue , Sojin Lee , Shiyue Tao , Geizecler Tomazetto , Kristin Yahner , Hui Liu , Matthew C. Lee , Mary Patricia Nowalk , Richard K. Zimmerman , Monika Johnson , William MacDonald , Erick Forno , Wei Chen , Nader Shaikh","doi":"10.1016/j.jinf.2025.106664","DOIUrl":"10.1016/j.jinf.2025.106664","url":null,"abstract":"<div><div>Prediction of outcomes of SARS-CoV-2 infection remains challenging, particularly in the early days following exposure. To better understand the heterogeneity of disease progression, we investigated the early immune response in the upper respiratory tract using transcriptomic analysis, comparing individuals who remained asymptomatic to those who developed symptoms of COVID-19. We conducted a study of 74 individuals (43 children, 31 adults) with confirmed SARS-CoV-2 infection. Mid-turbinate nasal swabs were collected during the first few days of infection and again one week later. We performed a paired analysis comparing baseline and follow-up nasal human gene expression. Additionally, we conducted a predictive analysis to identify transcripts associated with the development of symptomatic infection. From the differentially expressed transcripts in both analyses, we developed a predictive model to assess the likelihood of symptomatic disease. We also compared gene expression patterns between children and adults. A robust interferon response in the upper respiratory tract was strongly associated with the development of symptomatic infection. A panel of five interferon-stimulated genes (<em>TAP2</em>, <em>DDX60</em>, <em>IFIT5</em>, <em>APOL6</em>, and <em>IFI6</em>) predicted symptomatic infection with reasonable accuracy (area under the curve = 0.84). Notably, adaptive immune responses, including T-cell activation and cytokine signaling, differed substantially between children and adults. Our findings suggest that early measurement of interferon-stimulated gene expression may help identify individuals at risk of developing symptomatic COVID-19.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 1","pages":"Article 106664"},"PeriodicalIF":11.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jinf.2025.106659
TianYuan Zhu , JiaYu Guo , Dong Zhang , Li Weng , JinMin Peng , QiWen Yang , Bin Du
Objectives
To compare the clinical utility of DNA- and RNA-metagenomic next-generation sequencing (mNGS) for pathogen detection in lower respiratory tract infections (LRTIs), and evaluate strategies to optimize RNA-mNGS performance.
Methods
We retrospectively analyzed 82 patients with suspected LRTI undergoing simultaneous DNA-mNGS and RNA-mNGS testing. The concordance of two methods in detecting microorganisms was assessed. Performance in detecting causative pathogens was compared using multi-label classification metrics. Impacts of RNA-mNGS workflow adjustments were evaluated using mock samples.
Results
In a total of 196 microbial detections, DNA-mNGS and RNA-mNGS showed poor overall agreement (Cohen’s κ=0.166, p<0.01). In identifying causative pathogens, RNA-mNGS demonstrated significantly higher precision (1.00 vs. 0.50, p<0.05) and F1 scores (0.80 vs. 0.67, p<0.05) compared to DNA-mNGS. DNA-mNGS possessed higher sensitivity for bacteria, fungi, and atypical pathogens, while RNA-mNGS excelled in detecting RNA viruses. Improved RNA-mNGS sensitivity and significant DNA-RNA read correlations were observed in causative pathogens at high abundance. Neither homogenization nor increased sequencing depth improved RNA-mNGS testing.
Conclusions
DNA-mNGS and RNA-mNGS exhibited low overall consistency. However, RNA-mNGS showed superior precision in identifying causative pathogens in LRTI and additional capacity for RNA virus detections, while DNA-mNGS possessed essential sensitivity for low abundance pathogens.
{"title":"A comparative study of DNA- and RNA-metagenomic next-generation sequencing for pathogen detection in lower respiratory tract infections","authors":"TianYuan Zhu , JiaYu Guo , Dong Zhang , Li Weng , JinMin Peng , QiWen Yang , Bin Du","doi":"10.1016/j.jinf.2025.106659","DOIUrl":"10.1016/j.jinf.2025.106659","url":null,"abstract":"<div><h3>Objectives</h3><div>To compare the clinical utility of DNA- and RNA-metagenomic next-generation sequencing (mNGS) for pathogen detection in lower respiratory tract infections (LRTIs), and evaluate strategies to optimize RNA-mNGS performance.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 82 patients with suspected LRTI undergoing simultaneous DNA-mNGS and RNA-mNGS testing. The concordance of two methods in detecting microorganisms was assessed. Performance in detecting causative pathogens was compared using multi-label classification metrics. Impacts of RNA-mNGS workflow adjustments were evaluated using mock samples.</div></div><div><h3>Results</h3><div>In a total of 196 microbial detections, DNA-mNGS and RNA-mNGS showed poor overall agreement (Cohen’s κ=0.166, p<0.01). In identifying causative pathogens, RNA-mNGS demonstrated significantly higher precision (1.00 vs. 0.50, p<0.05) and F1 scores (0.80 vs. 0.67, p<0.05) compared to DNA-mNGS. DNA-mNGS possessed higher sensitivity for bacteria, fungi, and atypical pathogens, while RNA-mNGS excelled in detecting RNA viruses. Improved RNA-mNGS sensitivity and significant DNA-RNA read correlations were observed in causative pathogens at high abundance. Neither homogenization nor increased sequencing depth improved RNA-mNGS testing.</div></div><div><h3>Conclusions</h3><div>DNA-mNGS and RNA-mNGS exhibited low overall consistency. However, RNA-mNGS showed superior precision in identifying causative pathogens in LRTI and additional capacity for RNA virus detections, while DNA-mNGS possessed essential sensitivity for low abundance pathogens.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106659"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jinf.2025.106661
Lina Wang , Zhongyuan Zhao , Yuchi Zhao , Shengjie Dong , Shangxiang Feng , Li Cao , Kun Song
Objectives
The aim of this meta-analysis was to assess the diagnostic performance of metagenomic next-generation sequencing and targeted next-generation sequencing for periprosthetic joint infection (PJI).
Background
Next-generation sequencing (NGS) is increasingly used for diagnosing periprosthetic joint infection (PJI), but its clinical utility remains poorly defined. Discrepancies between metagenomic NGS (mNGS) and targeted NGS (tNGS) results pose a significant clinical challenge for PJI diagnosis. To address this, we conducted a systematic review and meta-analysis comparing the diagnostic accuracy of mNGS and tNGS for PJI.
Methods
This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus from inception through June 1, 2025. Two reviewers independently extracted data and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the hierarchical summary receiver operating characteristic curve (AUC) were calculated.
Results
Following screening and eligibility assessment, 23 studies were included in the analysis. The pooled sensitivity and specificity for diagnosing PJI were 0.89 (95% CI: 0.84–0.93) and 0.92 (95% CI: 0.89–0.95) for mNGS, and 0.84 (95% CI: 0.74–0.91) and 0.97 (95% CI: 0.88–0.99) for tNGS. The DORs were 58.56 (95% CI: 38.41–89.26) for mNGS and 106.67 (95% CI: 40.93–278.00) for tNGS. The areas under the summary receiver-operating characteristic curves (AUCs) were 0.935 (95% CI: 0.90–0.95) for mNGS and 0.911 (95% CI: 0.85–0.95) for tNGS. Comparisons of DOR and AUC between mNGS and tNGS revealed no statistically significant differences (P > 0.05).
Conclusions
This meta-analysis indicates that mNGS demonstrates higher sensitivity and a numerically greater AUC than tNGS for diagnosing PJI, with acceptable specificity, although the difference in AUC was not statistically significant. Conversely, tNGS exhibits higher specificity and DOR, alongside acceptable sensitivity, making it valuable for confirming PJI. Overall, the diagnostic accuracy of both next-generation sequencing (NGS) methods is comparable, with each possessing distinct advantages and limitations.
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