Pub Date : 2025-07-07DOI: 10.1016/j.jcv.2025.105833
Noah Brazer , Venice Servellita , Chengshi Jin , Abiodun Foresythe , Miriam Oseguera , Jenny Nguyen , Nanami Sumimoto , Hee Jae Huh , Andries Feder , Sanchita Bhattacharya , Surabhi Bhaskar , Alicia Sotomayor-Gonzalez , Prachi Saldhi , Chris Choi , Grace X. Li , Komal Gopchandani , Ashley Tippett , Hui-Mien Hsiao , Mark D. Gonzalez , Dalia Gulick , Charles Y. Chiu
We performed virus whole-genome sequencing of 6916 upper respiratory swabs from adults and children from March 2020 to May 2023 and collected clinical metadata to assess differences in SARS-CoV-2 variant severity and symptomatology. Multivariable logistic regression showed a severity peak with Delta, which had the highest likelihood of severe infection. In children, another peak was observed with BA.4/BA.5, which was associated with more severe infection than both prior (BA.1) and later (BQ.1, BF.7, and XBB) Omicron variants. In contrast, BA.4/BA.5 in adults was associated with less severe infection than BA.1. Genome-wide association studies revealed that nonstructural protein 5 (nsp5, also called 3C-chymotrypsin-like protease), the Paxlovid target, and the spike N-terminal domain were strongly associated with severity. Kmers (contiguous nucleotide sequences of a fixed length k) from these regions matched the prototype Wuhan sequence exactly, corroborating decreases in severity over time. One kmer in the spike gene region was conserved in Delta genomes, with the kmer retained in higher proportions in patients with more severe infection. Our results show, with the exception of Delta, decreases in severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.
{"title":"Differential severity of SARS-CoV-2 variant infections in children and adults with COVID-19","authors":"Noah Brazer , Venice Servellita , Chengshi Jin , Abiodun Foresythe , Miriam Oseguera , Jenny Nguyen , Nanami Sumimoto , Hee Jae Huh , Andries Feder , Sanchita Bhattacharya , Surabhi Bhaskar , Alicia Sotomayor-Gonzalez , Prachi Saldhi , Chris Choi , Grace X. Li , Komal Gopchandani , Ashley Tippett , Hui-Mien Hsiao , Mark D. Gonzalez , Dalia Gulick , Charles Y. Chiu","doi":"10.1016/j.jcv.2025.105833","DOIUrl":"10.1016/j.jcv.2025.105833","url":null,"abstract":"<div><div>We performed virus whole-genome sequencing of 6916 upper respiratory swabs from adults and children from March 2020 to May 2023 and collected clinical metadata to assess differences in SARS-CoV-2 variant severity and symptomatology. Multivariable logistic regression showed a severity peak with Delta, which had the highest likelihood of severe infection. In children, another peak was observed with BA.4/BA.5, which was associated with more severe infection than both prior (BA.1) and later (BQ.1, BF.7, and XBB) Omicron variants. In contrast, BA.4/BA.5 in adults was associated with less severe infection than BA.1. Genome-wide association studies revealed that nonstructural protein 5 (nsp5, also called 3C-chymotrypsin-like protease), the Paxlovid target, and the spike N-terminal domain were strongly associated with severity. Kmers (contiguous nucleotide sequences of a fixed length k) from these regions matched the prototype Wuhan sequence exactly, corroborating decreases in severity over time. One kmer in the spike gene region was conserved in Delta genomes, with the kmer retained in higher proportions in patients with more severe infection. Our results show, with the exception of Delta, decreases in severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"180 ","pages":"Article 105833"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-05DOI: 10.1016/j.jcv.2025.105832
Lance D. Presser , Amani Yousef , Elaine McCulloch , Julia Schaumburg , Adam Meijer
Background
Respiratory syncytial virus (RSV) is a common pathogen causing mostly mild-symptoms, but in young infants and elderly individuals it can lead to severe disease and death. After the SARS-CoV-2 pandemic, more focus on and testing of patients with respiratory symptoms occurred, which led to an increase in RSV detections. Also, newly developed vaccines and prophylactic and therapeutic antibodies against RSV have been approved for use, increasing attention on the need for quality RSV diagnostics.
Objectives
The goal of this study was a broad analysis of the external quality assessment (EQA) data for RSV using data from Quality Control for Molecular Diagnostics (QCMD).
Results
Using the QCMD data, performance of NAATs for detecting RSV was evaluated on an average of 67 laboratories per year, in an average of 21 countries across the WHO Europe region. The results of these EQAs show that the performance of laboratories for RSV molecular diagnostics in the WHO Europe region is good; overall correct scores for core samples between 96.8 % and 99.2 % for RSV-A and between 96.0 % and 100 % for RSV-B for the years 2020–2023. For the years 2020–2023, more tests were performed using commercial assays (63.5–82.0 %) than in-house assays (18.0–36.5 %).
Conclusions
Based on analysis of data from the QCMD RSV EQA program during the years 2020–2023, we conclude molecular diagnostics for RSV in laboratories from WHO Europe region are being performed with high-quality. However, with increases in testing, numerous diagnostic assays being used by laboratories, and possible viral changes to newly introduced vaccines and prophylactic/therapeutic antibodies, continued quality assessment of RSV diagnostics is recommended.
{"title":"Evaluation of molecular detection for respiratory syncytial viruses in World Health Organization Europe region laboratories, 2020–2023","authors":"Lance D. Presser , Amani Yousef , Elaine McCulloch , Julia Schaumburg , Adam Meijer","doi":"10.1016/j.jcv.2025.105832","DOIUrl":"10.1016/j.jcv.2025.105832","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory syncytial virus (RSV) is a common pathogen causing mostly mild-symptoms, but in young infants and elderly individuals it can lead to severe disease and death. After the SARS-CoV-2 pandemic, more focus on and testing of patients with respiratory symptoms occurred, which led to an increase in RSV detections. Also, newly developed vaccines and prophylactic and therapeutic antibodies against RSV have been approved for use, increasing attention on the need for quality RSV diagnostics.</div></div><div><h3>Objectives</h3><div>The goal of this study was a broad analysis of the external quality assessment (EQA) data for RSV using data from Quality Control for Molecular Diagnostics (QCMD).</div></div><div><h3>Results</h3><div>Using the QCMD data, performance of NAATs for detecting RSV was evaluated on an average of 67 laboratories per year, in an average of 21 countries across the WHO Europe region. The results of these EQAs show that the performance of laboratories for RSV molecular diagnostics in the WHO Europe region is good; overall correct scores for core samples between 96.8 % and 99.2 % for RSV-A and between 96.0 % and 100 % for RSV-B for the years 2020–2023. For the years 2020–2023, more tests were performed using commercial assays (63.5–82.0 %) than in-house assays (18.0–36.5 %).</div></div><div><h3>Conclusions</h3><div>Based on analysis of data from the QCMD RSV EQA program during the years 2020–2023, we conclude molecular diagnostics for RSV in laboratories from WHO Europe region are being performed with high-quality. However, with increases in testing, numerous diagnostic assays being used by laboratories, and possible viral changes to newly introduced vaccines and prophylactic/therapeutic antibodies, continued quality assessment of RSV diagnostics is recommended.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105832"},"PeriodicalIF":4.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1016/j.jcv.2025.105831
Hong Zhang , Jiaqiang Wang , Xiangqin Liu , Xueru Li , Xuexi Zeng , Qing Luo , Jialing Zhong
Immunodeficiency virus (HIV) antigen/antibody screening assays are highly sensitive and specific, but false-positive (FP) results remain a challenge. Understanding the prevalence and factors associated with these FP results is crucial, especially in high HIV burden regions. A retrospective cohort study of 370,291 patients screened with the ARCHITECT HIV Ag/Ab Combo assay at a Sichuan tertiary hospital (January 2022–December 2023) was conducted. We calculated HIV prevalence and assessed the test's FP rate, sensitivity, specificity and positive predictive value (PPV). Clinical characteristics and associated disease profiles of individuals with FP results were also analyzed. The overall HIV infection rate was 0.17 %. The FP rate for HIV screening was 0.08 %, with higher incidences observed among females, children (aged 0–17 years), and individuals aged 66 and older (P < 0.001). The mean signal-to-cutoff ratio (S/CO) in true positives (TPs) was significantly higher than that in FPs (576.63 vs. 1.94, P < 0.0001). A receiver operating characteristic (ROC)-determined cutoff of 19.6 provided optimal sensitivity (95.10 %) and specificity (99.99 %). FP results were associated with 18 disease categories, with digestive system disorders being the most prevalent. Malignant tumors, pregnancy, and cerebral infarction were also linked to FPs. These findings highlight the critical need for targeted screening strategies and more precise interpretation protocols to improve diagnostic accuracy. Furthermore, the link between FP results and various non-HIV-related diseases suggests that careful patient characterization may aid in identifying underlying conditions, thereby informing more effective clinical decision-making and public health interventions.
免疫缺陷病毒（HIV）抗原/抗体筛选测定是高度敏感和特异性的，但假阳性（FP）结果仍然是一个挑战。了解这些计划生育结果的流行情况和相关因素至关重要，特别是在艾滋病毒高负担地区。对四川省某三级医院（2022年1月- 2023年12月）采用ARCHITECT HIV Ag/Ab组合检测筛查的370,291例患者进行回顾性队列研究。我们计算HIV流行率，并评估该检测的FP率、敏感性、特异性和阳性预测值（PPV）。分析了FP结果个体的临床特征和相关疾病概况。总体HIV感染率为0.17%。HIV筛查的计划生育率为0.08%，在女性、儿童（0-17岁）和66岁及以上的人群中发病率较高(P <；0.001)。真阳性（TPs）的平均信号截止比（S/CO）显著高于FPs (576.63 vs. 1.94, P <；0.0001)。受试者工作特征（ROC）确定的截止值为19.6，提供了最佳的灵敏度（95.10%）和特异性（99.99%）。FP结果与18种疾病相关，其中消化系统疾病最为普遍。恶性肿瘤、妊娠和脑梗死也与FPs有关。这些发现强调了有针对性的筛查策略和更精确的解释方案的迫切需要，以提高诊断的准确性。此外，计划生育结果与各种非艾滋病毒相关疾病之间的联系表明，仔细描述患者特征可能有助于确定潜在疾病，从而为更有效的临床决策和公共卫生干预提供信息。
{"title":"False-positive results in fourth-generation HIV screening tests: Prevalence and associated factors in Sichuan, a high HIV burden province of China","authors":"Hong Zhang , Jiaqiang Wang , Xiangqin Liu , Xueru Li , Xuexi Zeng , Qing Luo , Jialing Zhong","doi":"10.1016/j.jcv.2025.105831","DOIUrl":"10.1016/j.jcv.2025.105831","url":null,"abstract":"<div><div>Immunodeficiency virus (HIV) antigen/antibody screening assays are highly sensitive and specific, but false-positive (FP) results remain a challenge. Understanding the prevalence and factors associated with these FP results is crucial, especially in high HIV burden regions. A retrospective cohort study of 370,291 patients screened with the ARCHITECT HIV Ag/Ab Combo assay at a Sichuan tertiary hospital (January 2022–December 2023) was conducted. We calculated HIV prevalence and assessed the test's FP rate, sensitivity, specificity and positive predictive value (PPV). Clinical characteristics and associated disease profiles of individuals with FP results were also analyzed. The overall HIV infection rate was 0.17 %. The FP rate for HIV screening was 0.08 %, with higher incidences observed among females, children (aged 0–17 years), and individuals aged 66 and older (<em>P</em> < 0.001). The mean signal-to-cutoff ratio (S/CO) in true positives (TPs) was significantly higher than that in FPs (576.63 vs. 1.94, <em>P</em> < 0.0001). A receiver operating characteristic (ROC)-determined cutoff of 19.6 provided optimal sensitivity (95.10 %) and specificity (99.99 %). FP results were associated with 18 disease categories, with digestive system disorders being the most prevalent. Malignant tumors, pregnancy, and cerebral infarction were also linked to FPs. These findings highlight the critical need for targeted screening strategies and more precise interpretation protocols to improve diagnostic accuracy. Furthermore, the link between FP results and various non-HIV-related diseases suggests that careful patient characterization may aid in identifying underlying conditions, thereby informing more effective clinical decision-making and public health interventions.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105831"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-25DOI: 10.1016/j.jcv.2025.105830
Devy M. Emperador , Leanna Sayyad , Monica Brady , Jessica Rowland , Inna Krapiunaya , Isabella Eckerle , Emmanuel Agogo , Daniel G. Bausch , Joel M. Montgomery , John D. Klena
Background
Nucleic acid-based assays are the diagnostic gold standard for filoviruses, including Ebola (EBOV) and Sudan (SUDV) viruses. However, outbreaks in areas with limited laboratory infrastructure highlight the need for simpler diagnostic tests that can be rapidly and safely used in the field.
Methods
We evaluated eight antigen rapid diagnostic tests (Ag-RDTs) for their ability to detect EBOV and SUDV. Analytical panels using virus cell slurries were used to assess limit of detection, and clinical samples were tested to determine sensitivity and specificity.
Results
Five Ag-RDTs detected EBOV and three detected SUDV, although clinical sensitivity was low (20–40 % for EBOV, 33 % for SUDV), improving only with higher viral loads. All assays demonstrated 100 % clinical specificity with no cross-reactivity.
Discussion
Although none of the evaluated Ag-RDTs are suitable for routine diagnosis, some may be useful in high viral load contexts such as cadaver testing. Our findings highlight the need to improve Ag-RDT sensitivity or develop high-sensitivity point-of-care molecular diagnostics.
{"title":"Laboratory evaluation of antigen rapid diagnostic tests to detect Ebola and Sudan viruses","authors":"Devy M. Emperador , Leanna Sayyad , Monica Brady , Jessica Rowland , Inna Krapiunaya , Isabella Eckerle , Emmanuel Agogo , Daniel G. Bausch , Joel M. Montgomery , John D. Klena","doi":"10.1016/j.jcv.2025.105830","DOIUrl":"10.1016/j.jcv.2025.105830","url":null,"abstract":"<div><h3>Background</h3><div>Nucleic acid-based assays are the diagnostic gold standard for filoviruses, including Ebola (EBOV) and Sudan (SUDV) viruses. However, outbreaks in areas with limited laboratory infrastructure highlight the need for simpler diagnostic tests that can be rapidly and safely used in the field.</div></div><div><h3>Methods</h3><div>We evaluated eight antigen rapid diagnostic tests (Ag-RDTs) for their ability to detect EBOV and SUDV. Analytical panels using virus cell slurries were used to assess limit of detection, and clinical samples were tested to determine sensitivity and specificity.</div></div><div><h3>Results</h3><div>Five Ag-RDTs detected EBOV and three detected SUDV, although clinical sensitivity was low (20–40 % for EBOV, 33 % for SUDV), improving only with higher viral loads. All assays demonstrated 100 % clinical specificity with no cross-reactivity.</div></div><div><h3>Discussion</h3><div>Although none of the evaluated Ag-RDTs are suitable for routine diagnosis, some may be useful in high viral load contexts such as cadaver testing. Our findings highlight the need to improve Ag-RDT sensitivity or develop high-sensitivity point-of-care molecular diagnostics.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105830"},"PeriodicalIF":4.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “A prospective study of plasma and bronchoalveolar lavage fluid CMV DNA load quantification for the diagnosis and outcome of CMV pneumonitis in immunocompromised hosts” [J. Clin. Virol. 155 (2022) 105243]","authors":"Gasit Saksirisampant , Theerasuk Kawamatawong , Kawin Promsombat , Warawut Sukkasem , Somprasong Liamsombut , Ekawat Pasomsub , Jackrapong Bruminhent","doi":"10.1016/j.jcv.2025.105829","DOIUrl":"10.1016/j.jcv.2025.105829","url":null,"abstract":"","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105829"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-18DOI: 10.1016/j.jcv.2025.105828
Evelyn Stelzl , Annemarie Berger , Sandra Ciesek , Antonella Olivero , Pietro Lampertico , Annapaola Callegaro , Sara Uceda Renteria , Albert Heim , Stephan W. Aberle , David N. Springer , Heiner Wedemeyer , Birgit Bremer , Lisa Sandmann , André Reinhardt , Beatrix Gey , Christian Früchtel , Harald H. Kessler
Background
The management of chronic hepatitis delta requires reliable test systems for the detection and quantification of hepatitis delta virus (HDV) RNA. The aim of this study was to obtain comparable results between seven European laboratories using the new RoboGene HDV RNA Quantification Kit 3.0 (Roboscreen GmbH) in combination with different test systems consisting of different nucleic acid extraction and amplification/detection platforms.
Methods
Correction factors (CFs) were determined to harmonize HDV RNA concentrations using the 1st WHO International Standard for HDV RNA (WHO IS HDV RNA). Limits of detection (LODs) were determined using a dilution series of the WHO IS HDV RNA. Reference material was used for accuracy testing. In addition, 20 dilutions of plasma sample pools obtained from untreated chronic hepatitis D patients were analyzed.
Results
The CFs ranged from 14 to 10,000 depending on the test system used. The calculated CFs were used for subsequent quantification. LODs ranged from <2.2 to >575 IU/mL. When accuracy was determined, the two lowest HDV RNA concentrations were not detected by the test system with the lowest sensitivity. When dilutions of pooled samples were tested, 7 of 140 results were reported as negative from all centers.
Conclusions
Test-specific CFs must be determined to harmonize HDV RNA quantification. Appropriate platforms for HDV RNA extraction are essential to achieve an adequate detection limit. Both high sensitivity and accurate quantification are important for the accurate monitoring of the response to existing anti-HDV treatment and for clinical trials of novel anti-HDV drugs.
背景：慢性丁型肝炎的管理需要可靠的检测系统来检测和定量丁型肝炎病毒（HDV） RNA。本研究的目的是在七个欧洲实验室之间使用新的RoboGene HDV RNA定量试剂盒3.0 (Roboscreen GmbH)，结合由不同核酸提取和扩增/检测平台组成的不同测试系统，获得可比结果。方法采用WHO第1版HDV RNA国际标准（WHO IS HDV RNA）测定校正因子（CFs）以协调HDV RNA浓度。检测限（lod）使用稀释系列WHO IS HDV RNA确定。采用标准物质进行精度检验。此外，还分析了未经治疗的慢性丁型肝炎患者血浆样品池的20个稀释度。根据所使用的测试系统，CFs的范围从14到10,000。计算出的cf用于随后的量化。LODs范围为2.2至575 IU/mL。当准确度确定时，两个最低的HDV RNA浓度没有被最低灵敏度的测试系统检测到。当对合并样本进行稀释检测时，所有中心报告的140个结果中有7个为阴性。结论必须确定病毒特异性CFs以协调HDV RNA的定量。适当的HDV RNA提取平台对于达到足够的检测限至关重要。高灵敏度和准确的定量对于准确监测现有抗hdv治疗的反应和新型抗hdv药物的临床试验至关重要。
{"title":"Accurate quantification using the new RoboGene HDV RNA Quantification Kit 3.0: A European multicenter study","authors":"Evelyn Stelzl , Annemarie Berger , Sandra Ciesek , Antonella Olivero , Pietro Lampertico , Annapaola Callegaro , Sara Uceda Renteria , Albert Heim , Stephan W. Aberle , David N. Springer , Heiner Wedemeyer , Birgit Bremer , Lisa Sandmann , André Reinhardt , Beatrix Gey , Christian Früchtel , Harald H. Kessler","doi":"10.1016/j.jcv.2025.105828","DOIUrl":"10.1016/j.jcv.2025.105828","url":null,"abstract":"<div><h3>Background</h3><div>The management of chronic hepatitis delta requires reliable test systems for the detection and quantification of hepatitis delta virus (HDV) RNA. The aim of this study was to obtain comparable results between seven European laboratories using the new RoboGene HDV RNA Quantification Kit 3.0 (Roboscreen GmbH) in combination with different test systems consisting of different nucleic acid extraction and amplification/detection platforms.</div></div><div><h3>Methods</h3><div>Correction factors (CFs) were determined to harmonize HDV RNA concentrations using the 1st WHO International Standard for HDV RNA (WHO IS HDV RNA). Limits of detection (LODs) were determined using a dilution series of the WHO IS HDV RNA. Reference material was used for accuracy testing. In addition, 20 dilutions of plasma sample pools obtained from untreated chronic hepatitis D patients were analyzed.</div></div><div><h3>Results</h3><div>The CFs ranged from 14 to 10,000 depending on the test system used. The calculated CFs were used for subsequent quantification. LODs ranged from <2.2 to >575 IU/mL. When accuracy was determined, the two lowest HDV RNA concentrations were not detected by the test system with the lowest sensitivity. When dilutions of pooled samples were tested, 7 of 140 results were reported as negative from all centers.</div></div><div><h3>Conclusions</h3><div>Test-specific CFs must be determined to harmonize HDV RNA quantification. Appropriate platforms for HDV RNA extraction are essential to achieve an adequate detection limit. Both high sensitivity and accurate quantification are important for the accurate monitoring of the response to existing anti-HDV treatment and for clinical trials of novel anti-HDV drugs.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105828"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-11DOI: 10.1016/j.jcv.2025.105826
Carine Bokop , Nisha Dhar , Alane Izu , Jayendrie Thaver-Kleitman , Nishi Prabdial-sing , Musa Mohammed Ali , Godwin Akaba , Hellen C. Barsosio , James A. Berkley , Manisha Madhai Beck , Tolossa E. Chaka , Clare L. Cutland , Phurb Dorji , Maksuda Islam , Adama Mamby Keita , Feleke Belachew Lema , Nubwa Medugu , Stella Mwakio , Stephen Obaro , Eyinade K. Olateju , Shabir A. Madhi
Background
Newborns infected with Hepatitis B Virus (HBV) are at risk of chronic liver disease and hepatocellular carcinoma.
Objectives
This study investigated the prevalence of HBV infection among pregnant women and cord blood Hepatitis B surface antigen (HBsAg) positivity of their newborns in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa.
Study design
Randomly selected paired maternal and cord blood samples (n = 101 each site) taken at delivery were tested for HBsAg and Hepatitis B extractable antigen (HBeAg) in the women using a chemiluminescent microparticle immunoassay. Similarly, cord blood sample of newborn was assessed for HBsAg reactivity. HBV DNA was quantified using the Xpert® HBV viral load assay, followed by genotyping.
Results
The overall prevalence of maternal HBsAg positivity was 5.5 % (95 %CI: 0.4 %–7.1 %; n = 50/909). HBsAg positivity was higher in African countries (7.3 %; 95 %CI: 5.4 %–9.6 %; n = 44/606) compared to South Asian countries (2.0 %; 95 %CI: 0.8 %–4.3 %; n = 6/303; p = 0.002). Relative to South Africa, there were higher odds of HBsAg sero-positivity in women from Mozambique ((aOR): 7.7, 95 %CI: 1.6 %–37.8 %) and Mali (aOR: 5.7; 95 %CI: 1.1 %–29.7 %). The rate of HBsAg positivity in cord blood of babies born to HBsAg positive women was 28.0 % (95 %CI: 17.1 %–42.3 %; n = 14/50), including 31.8 % (95 %CI: 19.5–47.4 %; n = 14/44) in African countries. No cord blood HBsAg positivity was observed in South Asia. Genotypic analysis revealed HBV genotypes A (41.7 %) and E (58.3 %) were pre-dominant.
Conclusion
The high rate of cord blood positivity (28.0 %) for HBsAg underscores the urgency of enhancing HBV prevention strategies to meet the World Health Organization’s target of a 90 % reduction in new HBV infections by 2030.
{"title":"Prevalence of hepatitis B virus infection among pregnant women and cord blood hepatitis B surface antigen positive newborns in sub-Saharan Africa and South Asia","authors":"Carine Bokop , Nisha Dhar , Alane Izu , Jayendrie Thaver-Kleitman , Nishi Prabdial-sing , Musa Mohammed Ali , Godwin Akaba , Hellen C. Barsosio , James A. Berkley , Manisha Madhai Beck , Tolossa E. Chaka , Clare L. Cutland , Phurb Dorji , Maksuda Islam , Adama Mamby Keita , Feleke Belachew Lema , Nubwa Medugu , Stella Mwakio , Stephen Obaro , Eyinade K. Olateju , Shabir A. Madhi","doi":"10.1016/j.jcv.2025.105826","DOIUrl":"10.1016/j.jcv.2025.105826","url":null,"abstract":"<div><h3>Background</h3><div>Newborns infected with Hepatitis B Virus (HBV) are at risk of chronic liver disease and hepatocellular carcinoma.</div></div><div><h3>Objectives</h3><div>This study investigated the prevalence of HBV infection among pregnant women and cord blood Hepatitis B surface antigen (HBsAg) positivity of their newborns in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa.</div></div><div><h3>Study design</h3><div>Randomly selected paired maternal and cord blood samples (n = 101 each site) taken at delivery were tested for HBsAg and Hepatitis B extractable antigen (HBeAg) in the women using a chemiluminescent microparticle immunoassay. Similarly, cord blood sample of newborn was assessed for HBsAg reactivity. HBV DNA was quantified using the Xpert® HBV viral load assay, followed by genotyping.</div></div><div><h3>Results</h3><div>The overall prevalence of maternal HBsAg positivity was 5.5 % (95 %CI: 0.4 %–7.1 %; n = 50/909). HBsAg positivity was higher in African countries (7.3 %; 95 %CI: 5.4 %–9.6 %; n = 44/606) compared to South Asian countries (2.0 %; 95 %CI: 0.8 %–4.3 %; n = 6/303; p = 0.002). Relative to South Africa, there were higher odds of HBsAg sero-positivity in women from Mozambique ((aOR): 7.7, 95 %CI: 1.6 %–37.8 %) and Mali (aOR: 5.7; 95 %CI: 1.1 %–29.7 %). The rate of HBsAg positivity in cord blood of babies born to HBsAg positive women was 28.0 % (95 %CI: 17.1 %–42.3 %; n = 14/50), including 31.8 % (95 %CI: 19.5–47.4 %; n = 14/44) in African countries. No cord blood HBsAg positivity was observed in South Asia. Genotypic analysis revealed HBV genotypes A (41.7 %) and E (58.3 %) were pre-dominant.</div></div><div><h3>Conclusion</h3><div>The high rate of cord blood positivity (28.0 %) for HBsAg underscores the urgency of enhancing HBV prevention strategies to meet the World Health Organization’s target of a 90 % reduction in new HBV infections by 2030.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105826"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-11DOI: 10.1016/j.jcv.2025.105825
Conglin Zhao , Shuai Tao , Mengxin Lu , Weixia Li , Han Zhao , Shuangshuang Sun , Weijia Lin , Chong Chen , Qiang Li , Yuxian Huang , Liang Chen
Background
Hepatitis E virus (HEV) is a significant public health concern worldwide. Current diagnostic methods for HEV infection have limitations in terms of accessibility and timeliness.
Objective
To assess the diagnostic performance of the Wantai urinary HEV antigen (Ag) colloidal gold immunochromatographic assay (GICA) in HEV infection.
Methods
This prospective study enrolled 150 patients with suspected acute hepatitis E and 50 healthy controls. Paired urine, fecal, and serum samples were collected during initial clinical evaluation. Serum and fecal HEV RNA levels were quantified via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), with genotyping performed by nested RT-PCR. Serum anti-HEV IgM/IgG levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), and urinary HEV antigen was detected using GICA. Diagnostic accuracy metrics were calculated against the reference standard of HEV RNA detection.
Results
HEV RNA was detected in 58 % (87/150) of suspected cases. All successfully genotyped cases (69 %, 60/87) were HEV genotype 4. All healthy controls tested negative for HEV RNA and urinary HEV Ag.The urinary HEV Ag GICA showed 98.9 % sensitivity and 87.6 % specificity, with high concordance with RT-qPCR (Kappa = 0.85). Longitudinal follow-up revealed viral clearance and liver function normalization in most patients within 3–4 weeks post-symptom onset. 85.7 % of patients achieved urinary HEV Ag negative conversion within 6–7 weeks, while anti-HEV IgM remained positive in all patients at follow-up conclusion.
Conclusion
Urinary HEV Ag GICA demonstrates high diagnostic reliability for acute HEV infection, offering a practical non-invasive option for resource-limited settings.
戊型肝炎病毒（HEV）是世界范围内一个重要的公共卫生问题。目前的HEV感染诊断方法在可及性和及时性方面存在局限性。目的评价万台尿HEV抗原（Ag）胶体金免疫层析法（GICA）对HEV感染的诊断价值。方法本前瞻性研究纳入150例疑似急性戊型肝炎患者和50例健康对照。在最初的临床评估中收集成对的尿液、粪便和血清样本。通过逆转录-定量聚合酶链反应（RT-qPCR）定量血清和粪便HEV RNA水平，并采用巢式RT-PCR进行基因分型。采用酶联免疫吸附试验（ELISA）检测血清抗HEV IgM/IgG水平，采用GICA检测尿HEV抗原。根据HEV RNA检测参考标准计算诊断准确性指标。结果58.8%（87/150）的疑似病例检出shev RNA。所有成功分型的病例（69%,60/87）均为HEV基因4型。所有健康对照者的HEV RNA和尿HEV Ag检测均为阴性。尿HEV Ag GICA的敏感性为98.9%，特异性为87.6%，与RT-qPCR具有较高的一致性（Kappa = 0.85）。纵向随访显示，大多数患者在症状出现后3-4周内病毒清除和肝功能恢复正常。85.7%的患者在6-7周内实现尿HEV Ag阴性转化，而在随访结束时，所有患者的抗HEV IgM均为阳性。结论尿HEV Ag GICA对急性HEV感染具有较高的诊断可靠性，为资源有限的环境提供了一种实用的非侵入性选择。
{"title":"Evaluation of urinary hepatitis E virus antigen colloidal gold immunochromatographic assay in clinical diagnosis of hepatitis E virus infection","authors":"Conglin Zhao , Shuai Tao , Mengxin Lu , Weixia Li , Han Zhao , Shuangshuang Sun , Weijia Lin , Chong Chen , Qiang Li , Yuxian Huang , Liang Chen","doi":"10.1016/j.jcv.2025.105825","DOIUrl":"10.1016/j.jcv.2025.105825","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis E virus (HEV) is a significant public health concern worldwide. Current diagnostic methods for HEV infection have limitations in terms of accessibility and timeliness.</div></div><div><h3>Objective</h3><div>To assess the diagnostic performance of the Wantai urinary HEV antigen (Ag) colloidal gold immunochromatographic assay (GICA) in HEV infection.</div></div><div><h3>Methods</h3><div>This prospective study enrolled 150 patients with suspected acute hepatitis E and 50 healthy controls. Paired urine, fecal, and serum samples were collected during initial clinical evaluation. Serum and fecal HEV RNA levels were quantified via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), with genotyping performed by nested RT-PCR. Serum anti-HEV IgM/IgG levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), and urinary HEV antigen was detected using GICA. Diagnostic accuracy metrics were calculated against the reference standard of HEV RNA detection.</div></div><div><h3>Results</h3><div>HEV RNA was detected in 58 % (87/150) of suspected cases. All successfully genotyped cases (69 %, 60/87) were HEV genotype 4. All healthy controls tested negative for HEV RNA and urinary HEV Ag.The urinary HEV Ag GICA showed 98.9 % sensitivity and 87.6 % specificity, with high concordance with RT-qPCR (Kappa = 0.85). Longitudinal follow-up revealed viral clearance and liver function normalization in most patients within 3–4 weeks post-symptom onset. 85.7 % of patients achieved urinary HEV Ag negative conversion within 6–7 weeks, while anti-HEV IgM remained positive in all patients at follow-up conclusion.</div></div><div><h3>Conclusion</h3><div>Urinary HEV Ag GICA demonstrates high diagnostic reliability for acute HEV infection, offering a practical non-invasive option for resource-limited settings.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105825"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-11DOI: 10.1016/j.jcv.2025.105824
Elizabeth White , Mehyar Khair Baik , Syeda Farah Zahir , Christopher C. Blyth , Jeremy Carr , Nigel W. Crawford , Joshua R. Francis , Helen S. Marshall , Emma Carey , Kristine Macartney , Brendan McMullan , Nicholas Wood , Philip N. Britton , Julia E. Clark , on behalf of the PAEDS network
Background
Management and outcomes of children hospitalised with acute SARS-CoV-2 infection may differ throughout the pandemic or with admission type (clinical COVID-19, incidental COVID-19 or nosocomial infection).
Objectives
Describe the severity, management and outcomes of hospitalised children with acute SARS-CoV-2 infection in Australia across the first 4 years of the pandemic and compare between admission types, SARS-CoV-2 variants, age groups and immune status.
Study design
A multi-centre prospective cohort study of 6009 children aged 0–16 years between January 2020 and June 2023.
Results
Most children (84.3 %) did not receive respiratory support, 33.4 % received antibiotics and 8 % were admitted to intensive care unit (ICU). Infants <6 months old were more likely to be admitted with clinical COVID than older children (12–16 years). Older children were more likely to receive antibiotics (27.8 % vs 43.9 %), corticosteroids (11.3 % vs 34.1%) or ICU admission (5.2 % vs 13.5 %). Compared to immunocompetent children, the immunosuppressed (7.7 %) were more likely to have nosocomial infection (9.5 % vs 3.9 %), receive antibiotics (57 % vs 25 %) or antivirals (18 % vs 4.4 %), but less likely to require respiratory support (93.4 % vs 83.8 %) or ICU admission (3.5 % vs 8 %). Children with nosocomial SARS-CoV-2 infection had higher rates of invasive ventilation (8 %) and ICU admission (21 %) compared to those with clinical (2.1 % and 7.1 % respectively) or incidental COVID-19 (4.8 % and 9.1 % respectively).
Conclusions
Acute COVID-19 generally caused mild disease in hospitalised children, with management and outcomes differing by age and admission type. Similar outcomes were observed across the pandemic. Nosocomial SARS-CoV-2 infection was associated with more severe disease.
{"title":"Management and outcomes of children hospitalised with COVID-19 including incidental and nosocomial infections in Australia 2020–2023: A national surveillance study","authors":"Elizabeth White , Mehyar Khair Baik , Syeda Farah Zahir , Christopher C. Blyth , Jeremy Carr , Nigel W. Crawford , Joshua R. Francis , Helen S. Marshall , Emma Carey , Kristine Macartney , Brendan McMullan , Nicholas Wood , Philip N. Britton , Julia E. Clark , on behalf of the PAEDS network","doi":"10.1016/j.jcv.2025.105824","DOIUrl":"10.1016/j.jcv.2025.105824","url":null,"abstract":"<div><h3>Background</h3><div>Management and outcomes of children hospitalised with acute SARS-CoV-2 infection may differ throughout the pandemic or with admission type (clinical COVID-19, incidental COVID-19 or nosocomial infection).</div></div><div><h3>Objectives</h3><div>Describe the severity, management and outcomes of hospitalised children with acute SARS-CoV-2 infection in Australia across the first 4 years of the pandemic and compare between admission types, SARS-CoV-2 variants, age groups and immune status.</div></div><div><h3>Study design</h3><div>A multi-centre prospective cohort study of 6009 children aged 0–16 years between January 2020 and June 2023.</div></div><div><h3>Results</h3><div>Most children (84.3 %) did not receive respiratory support, 33.4 % received antibiotics and 8 % were admitted to intensive care unit (ICU). Infants <6 months old were more likely to be admitted with clinical COVID than older children (12–16 years). Older children were more likely to receive antibiotics (27.8 % vs 43.9 %), corticosteroids (11.3 % vs 34.1%) or ICU admission (5.2 % vs 13.5 %). Compared to immunocompetent children, the immunosuppressed (7.7 %) were more likely to have nosocomial infection (9.5 % vs 3.9 %), receive antibiotics (57 % vs 25 %) or antivirals (18 % vs 4.4 %), but less likely to require respiratory support (93.4 % vs 83.8 %) or ICU admission (3.5 % vs 8 %). Children with nosocomial SARS-CoV-2 infection had higher rates of invasive ventilation (8 %) and ICU admission (21 %) compared to those with clinical (2.1 % and 7.1 % respectively) or incidental COVID-19 (4.8 % and 9.1 % respectively).</div></div><div><h3>Conclusions</h3><div>Acute COVID-19 generally caused mild disease in hospitalised children, with management and outcomes differing by age and admission type. Similar outcomes were observed across the pandemic. Nosocomial SARS-CoV-2 infection was associated with more severe disease.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105824"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The occurrence of respiratory infections caused by seasonal viruses influenza A/B, RSV and SARS-CoV-2 has increased the demand for rapid diagnostic assays. Comparative performance data of such assays is required.
Methods
In this retrospective study, clinical samples were tested with the STANDARD™ M10 Flu/RSV/SARS-CoV-2 test and the novel Savanna® Respiratory Viral Panel-4 tests, with Xpert® Xpress SARS-CoV-2/Flu/RSV as the reference. All three are RT-PCR tests suitable for point-of-care testing. Discordant results on the Savanna assay were retested with a new research-use-only protocol. Serial dilution testing for all three was performed with an external control.
Results
A total of 141 clinical samples, including 106 specimens positive for at least one virus, were analyzed. The M10 assay showed sensitivities of 100 %, 95.7 %, 97.1 % and 97.0 % for influenza A, B, RSV and SARS-CoV-2, respectively. The Savanna assay showed sensitivities of 92.6 %, 95.7 %, 100 % and 90.9 %. Both assays exhibited high specificity (≥99 %), except for the Savanna assay’s lower specificity for RSV (94.2 %) and SARS-CoV-2 (94.3 %). Savanna had a higher retest rate (5.0 %), while M10 produced only conclusive results. Serial dilution testing showed that Xpert detected three viruses more effectively than the other assays.
Conclusion
Both M10 and Savanna performed well for influenza A/B, but M10 was superior for RSV and SARS-CoV-2 due to false positives with Savanna. The new Savanna protocol showed promise, but further studies are required to confirm these findings. Xpert assay was the most sensitive for detecting low viral amounts.
{"title":"Comparative evaluation of STANDARD™ M10 Flu/RSV/SARS-CoV-2 and Savanna® Respiratory Viral Panel-4 assays for the rapid molecular diagnosis of influenza A/B virus, respiratory syncytial virus and SARS-CoV-2","authors":"Juulia Suominen, Raisa Loginov, Hannimari Kallio-Kokko","doi":"10.1016/j.jcv.2025.105827","DOIUrl":"10.1016/j.jcv.2025.105827","url":null,"abstract":"<div><h3>Background</h3><div>The occurrence of respiratory infections caused by seasonal viruses influenza A/B, RSV and SARS-CoV-2 has increased the demand for rapid diagnostic assays. Comparative performance data of such assays is required.</div></div><div><h3>Methods</h3><div>In this retrospective study, clinical samples were tested with the STANDARD™ M10 Flu/RSV/SARS-CoV-2 test and the novel Savanna® Respiratory Viral Panel-4 tests, with Xpert® Xpress SARS-CoV-2/Flu/RSV as the reference. All three are RT-PCR tests suitable for point-of-care testing. Discordant results on the Savanna assay were retested with a new research-use-only protocol. Serial dilution testing for all three was performed with an external control.</div></div><div><h3>Results</h3><div>A total of 141 clinical samples, including 106 specimens positive for at least one virus, were analyzed. The M10 assay showed sensitivities of 100 %, 95.7 %, 97.1 % and 97.0 % for influenza A, B, RSV and SARS-CoV-2, respectively. The Savanna assay showed sensitivities of 92.6 %, 95.7 %, 100 % and 90.9 %. Both assays exhibited high specificity (≥99 %), except for the Savanna assay’s lower specificity for RSV (94.2 %) and SARS-CoV-2 (94.3 %). Savanna had a higher retest rate (5.0 %), while M10 produced only conclusive results. Serial dilution testing showed that Xpert detected three viruses more effectively than the other assays.</div></div><div><h3>Conclusion</h3><div>Both M10 and Savanna performed well for influenza A/B, but M10 was superior for RSV and SARS-CoV-2 due to false positives with Savanna. The new Savanna protocol showed promise, but further studies are required to confirm these findings. Xpert assay was the most sensitive for detecting low viral amounts.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"179 ","pages":"Article 105827"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号