Pub Date : 2025-03-17DOI: 10.1016/j.jcv.2025.105781
Cyrus Hawkins , Elizabeth Waddilove , Philippa C. Matthews , Marion Delphin
Background
Outcomes of chronic Hepatitis B (CHB) infection have been increasingly associated with various metabolic syndromes, including metabolic-dysfunction associated steatotic liver disease (MASLD), with a potential for impact on liver disease progression. There is some evidence that metformin, a widely used anti-diabetic drug, may reduce hepatocellular carcinoma (HCC) incidence in people living with Hepatitis B Virus (HBV), but with little to no evidence of impact on the virus itself in vivo. However, previous in vitro studies suggest metformin may have a direct impact on HBV replication, although the mechanism remains unclear.
Objectives
We aimed to investigate the impact of metformin on HBV replication in vitro.
Study design
Hepatocyte cell lines constitutively expressing HBV (HepAD38) were treated once or thrice with escalating doses of metformin, using lamivudine and water as controls. We monitored cellular cytotoxicity as well as HBV biomarkers (HBeAg, HBsAg, HBV DNA and RNA) throughout the assay.
Results
We did not observe any impact of metformin on HBV replication after a single dose or three repeated treatments.
Conclusions
In HepAD38 cells, HBV replication is not impacted by metformin treatment. This contrasts with prior in vitro data but is in line with clinical evidence that suggests metformin acts through an influence on liver disease progression rather than a direct antiviral impact on HBV itself.
{"title":"Impact of metformin on HBV replication: No evidence of suppression in vitro","authors":"Cyrus Hawkins , Elizabeth Waddilove , Philippa C. Matthews , Marion Delphin","doi":"10.1016/j.jcv.2025.105781","DOIUrl":"10.1016/j.jcv.2025.105781","url":null,"abstract":"<div><h3>Background</h3><div>Outcomes of chronic Hepatitis B (CHB) infection have been increasingly associated with various metabolic syndromes, including metabolic-dysfunction associated steatotic liver disease (MASLD), with a potential for impact on liver disease progression. There is some evidence that metformin, a widely used anti-diabetic drug, may reduce hepatocellular carcinoma (HCC) incidence in people living with Hepatitis B Virus (HBV), but with little to no evidence of impact on the virus itself <em>in vivo</em>. However, previous <em>in vitro</em> studies suggest metformin may have a direct impact on HBV replication, although the mechanism remains unclear.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the impact of metformin on HBV replication <em>in vitro</em>.</div></div><div><h3>Study design</h3><div>Hepatocyte cell lines constitutively expressing HBV (HepAD38) were treated once or thrice with escalating doses of metformin, using lamivudine and water as controls. We monitored cellular cytotoxicity as well as HBV biomarkers (HBeAg, HBsAg, HBV DNA and RNA) throughout the assay.</div></div><div><h3>Results</h3><div>We did not observe any impact of metformin on HBV replication after a single dose or three repeated treatments.</div></div><div><h3>Conclusions</h3><div>In HepAD38 cells, HBV replication is not impacted by metformin treatment. This contrasts with prior <em>in vitro</em> data but is in line with clinical evidence that suggests metformin acts through an influence on liver disease progression rather than a direct antiviral impact on HBV itself.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105781"},"PeriodicalIF":4.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-11DOI: 10.1016/j.jcv.2025.105778
Ichiro Morioka , Yasumasa Kakei , Takumi Imai , Kazumichi Fujioka , Naoto Takahashi , Tetsushi Yoshikawa , Hiroyuki Moriuchi , Yoshinori Ito , Akira Oka , for the Japanese Congenital Cytomegalovirus Study Group
Objective
To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months.
Study design
We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of "Improved hearing" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed.
Results
At 3 years, among 48 ears from 24 infants, the number of "improved hearing," which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including “maintaining normal hearing” or “maintaining normal hearing or the same degree of hearing impairment”, the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period.
Conclusion
Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.
{"title":"Three-year hearing outcomes in infants with congenital cytomegalovirus disease treated with oral valganciclovir: Interim results of a six-year follow-up study in Japan","authors":"Ichiro Morioka , Yasumasa Kakei , Takumi Imai , Kazumichi Fujioka , Naoto Takahashi , Tetsushi Yoshikawa , Hiroyuki Moriuchi , Yoshinori Ito , Akira Oka , for the Japanese Congenital Cytomegalovirus Study Group","doi":"10.1016/j.jcv.2025.105778","DOIUrl":"10.1016/j.jcv.2025.105778","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months.</div></div><div><h3>Study design</h3><div>We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of \"Improved hearing\" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed.</div></div><div><h3>Results</h3><div>At 3 years, among 48 ears from 24 infants, the number of \"improved hearing,\" which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including “maintaining normal hearing” or “maintaining normal hearing or the same degree of hearing impairment”, the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period.</div></div><div><h3>Conclusion</h3><div>Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105778"},"PeriodicalIF":4.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610261","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 : 2025-03-11DOI: 10.1016/j.jcv.2025.105779
Alissa Moore , Mariam El-Zein , Ann N. Burchell , Pierre-Paul Tellier , François Coutlée , Eduardo L. Franco
Background
Understanding human papillomavirus (HPV) transmission dynamics within couples is necessary for optimal vaccine catch-up strategies. We used data from the Transmission Reduction and Prevention with HPV Vaccination (TRAP-HPV) study to estimate sex-specific incidence and transmission rates.
Methods
The TRAP-HPV study enrolled (2014–2022) new (≤6 months) heterosexual couples aged 18+ in Montreal, Canada. The study employed a 2 × 2 factorial design. Participants (n = 308) were randomized into four groups: neither partner vaccinated against HPV, only the male partner vaccinated against HPV, only the female partner vaccinated against HPV, or both partners vaccinated against HPV. Genital samples, collected at 0, 2, 4, 6, 9, and 12 months, were genotyped for 36 HPV types. We performed time-to-event analyses for vaccine-targeted HPVs (6/11/16/18/31/33/45/52/58) and HPVs phylogenetically related (35/39/44/59/67/68/70) and unrelated (26/34/40/42/51/53/54/56/61/62/66/69/71/72/73/81/82/83/84/89) to vaccine-targeted types, using type-specific HPV infections as the unit of analysis.
Results
Participants had a mean age of 25.5 years (SD 6.0), and a median of 6 (IQR: 2–15) lifetime sexual partners. Among males, incidence rates (in events/1000 months) were 0.99 (95 % CI: 0.17–3.07) and 1.67 (95 % CI: 0.75–3.51) in the two groups with vaccinated males versus 2.42 (95 % CI: 0.97–7.63) and 3.35 (95 % CI: 1.95–6.30) in the groups with unvaccinated males. Results were similar for the three HPV groups.
Conclusions
There was no consistent pattern of protection against incident HPV detection in females and no indication that recent vaccination was associated with lower transmission in discordant couples or with protection for one’s partner. Findings should not be generalized to younger populations.
{"title":"Human papillomavirus incidence and transmission by vaccination status among heterosexual couples","authors":"Alissa Moore , Mariam El-Zein , Ann N. Burchell , Pierre-Paul Tellier , François Coutlée , Eduardo L. Franco","doi":"10.1016/j.jcv.2025.105779","DOIUrl":"10.1016/j.jcv.2025.105779","url":null,"abstract":"<div><h3>Background</h3><div>Understanding human papillomavirus (HPV) transmission dynamics within couples is necessary for optimal vaccine catch-up strategies. We used data from the Transmission Reduction and Prevention with HPV Vaccination (TRAP-HPV) study to estimate sex-specific incidence and transmission rates.</div></div><div><h3>Methods</h3><div>The TRAP-HPV study enrolled (2014–2022) new (≤6 months) heterosexual couples aged 18+ in Montreal, Canada. The study employed a 2 × 2 factorial design. Participants (n = 308) were randomized into four groups: neither partner vaccinated against HPV, only the male partner vaccinated against HPV, only the female partner vaccinated against HPV, or both partners vaccinated against HPV. Genital samples, collected at 0, 2, 4, 6, 9, and 12 months, were genotyped for 36 HPV types. We performed time-to-event analyses for vaccine-targeted HPVs (6/11/16/18/31/33/45/52/58) and HPVs phylogenetically related (35/39/44/59/67/68/70) and unrelated (26/34/40/42/51/53/54/56/61/62/66/69/71/72/73/81/82/83/84/89) to vaccine-targeted types, using type-specific HPV infections as the unit of analysis.</div></div><div><h3>Results</h3><div>Participants had a mean age of 25.5 years (SD 6.0), and a median of 6 (IQR: 2–15) lifetime sexual partners. Among males, incidence rates (in events/1000 months) were 0.99 (95 % CI: 0.17–3.07) and 1.67 (95 % CI: 0.75–3.51) in the two groups with vaccinated males versus 2.42 (95 % CI: 0.97–7.63) and 3.35 (95 % CI: 1.95–6.30) in the groups with unvaccinated males. Results were similar for the three HPV groups.</div></div><div><h3>Conclusions</h3><div>There was no consistent pattern of protection against incident HPV detection in females and no indication that recent vaccination was associated with lower transmission in discordant couples or with protection for one’s partner. Findings should not be generalized to younger populations.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105779"},"PeriodicalIF":4.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-07DOI: 10.1016/j.jcv.2025.105775
Karine Alamé , Quentin Le Hingrat , Pierre Catoire , Richard Chocron , Xavier Eyer , Christelle Hermand , Judith Gorlicki , Sarah Addou , Ségolène Brichler , Maud Salmona , David Veyer , Stéphane Marot , Aurélie Schnuriger , Yonathan Freund , Donia Bouzid
Objective
In recent years, there has been increased awareness of the impact of respiratory syncytial virus (RSV) on adult health, especially in elderly patients. Unlike influenza infection, its presentation and patient outcomes are not well studied. The aim of this study was to compare clinical outcomes in emergency department patients infected by RSV vs influenza.
Methods
This was a multicenter retrospective study in seven emergency departments (ED) in France. Patients with a laboratory-confirmed RSV or influenza infection in the ED were included between January 2017 and December 2022. The primary endpoint was in-hospital mortality truncated at day 28. Secondary endpoints included one year occurrence of thrombo-embolic event, acute coronary syndrome, and stroke.
Results
3397 patient charts were screened, and 3224 were analyzed. Of these, 551 (17 %) patients had RSV-positive PCR, and 2673 (83 %) had influenza-positive PCR. Patients with RSV were older (median age 73 vs. 68; difference, −5.00 % points [CI, −4.0 to −6.0 % points])), and had more comorbidities (15.0 % vs 22.0 % difference, −6.92 % points [CI, −10.6 to −3.21 % points])), compared to those with influenza. There was no significant difference in in-hospital mortality rate at day 28: 3.82 % for influenza vs. 4.72 % for RSV (adjusted OR 0.93, 95 %CI [0.59–1.46] p = 0.73). There was no significant difference in the occurrence of the secondary endpoints.
Conclusions
In this large study of ED patients, although RSV patients were more fragile, no significant differences were found in in-hospital mortality or the occurrence of cardiovascular or thromboembolic events between RSV and influenza infections.
目的近年来，呼吸道合胞病毒（RSV）对成人特别是老年患者健康影响的认识日益提高。与流感感染不同，其表现和患者预后尚未得到很好的研究。本研究的目的是比较急诊科感染RSV和流感患者的临床结果。方法对法国7个急诊科（ED）进行多中心回顾性研究。纳入了2017年1月至2022年12月期间在急诊科实验室确诊的RSV或流感感染患者。主要终点是第28天的住院死亡率。次要终点包括一年内发生血栓栓塞事件、急性冠状动脉综合征和中风。结果共筛选患者病历3397份，分析病历3224份。其中，551例（17%）患者PCR呈rsv阳性，2673例（83%）PCR呈流感阳性。RSV患者年龄较大(中位年龄73 vs 68；差异，−5.00个百分点[CI，−4.0至−6.0个百分点])))，并且与流感患者相比有更多的合并症（15.0% vs 22.0%差异，−6.92个百分点[CI，−10.6至−3.21个百分点]）)。第28天的住院死亡率无显著差异：流感患者为3.82%，RSV患者为4.72%（校正OR 0.93, 95% CI [0.59-1.46] p = 0.73）。次要终点的发生率无显著差异。结论在这项针对ED患者的大型研究中，虽然RSV患者更脆弱，但在院内死亡率、心血管或血栓栓塞事件的发生方面，RSV与流感感染之间没有显著差异。
{"title":"Comparison of patients presenting to emergency departments infected with respiratory syncytial virus versus influenza virus: A retrospective cohort study","authors":"Karine Alamé , Quentin Le Hingrat , Pierre Catoire , Richard Chocron , Xavier Eyer , Christelle Hermand , Judith Gorlicki , Sarah Addou , Ségolène Brichler , Maud Salmona , David Veyer , Stéphane Marot , Aurélie Schnuriger , Yonathan Freund , Donia Bouzid","doi":"10.1016/j.jcv.2025.105775","DOIUrl":"10.1016/j.jcv.2025.105775","url":null,"abstract":"<div><h3>Objective</h3><div>In recent years, there has been increased awareness of the impact of respiratory syncytial virus (RSV) on adult health, especially in elderly patients. Unlike influenza infection, its presentation and patient outcomes are not well studied. The aim of this study was to compare clinical outcomes in emergency department patients infected by RSV vs influenza.</div></div><div><h3>Methods</h3><div>This was a multicenter retrospective study in seven emergency departments (ED) in France. Patients with a laboratory-confirmed RSV or influenza infection in the ED were included between January 2017 and December 2022. The primary endpoint was in-hospital mortality truncated at day 28. Secondary endpoints included one year occurrence of thrombo-embolic event, acute coronary syndrome, and stroke.</div></div><div><h3>Results</h3><div>3397 patient charts were screened, and 3224 were analyzed. Of these, 551 (17 %) patients had RSV-positive PCR, and 2673 (83 %) had influenza-positive PCR. Patients with RSV were older (median age 73 vs. 68; difference, −5.00 % points [CI, −4.0 to −6.0 % points])), and had more comorbidities (15.0 % vs 22.0 % difference, −6.92 % points [CI, −10.6 to −3.21 % points])), compared to those with influenza. There was no significant difference in in-hospital mortality rate at day 28: 3.82 % for influenza vs. 4.72 % for RSV (adjusted OR 0.93, 95 %CI [0.59–1.46] p = 0.73). There was no significant difference in the occurrence of the secondary endpoints.</div></div><div><h3>Conclusions</h3><div>In this large study of ED patients, although RSV patients were more fragile, no significant differences were found in in-hospital mortality or the occurrence of cardiovascular or thromboembolic events between RSV and influenza infections.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105775"},"PeriodicalIF":4.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579492","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 : 2025-03-06DOI: 10.1016/j.jcv.2025.105776
Joachim Bourdin , Maud Salmona , Nadhira Fidouh , Sébastien Fouéré , Jérôme LeGoff , Sarah Maylin
Background
The landscape of diagnostic assays for detecting herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) antibodies (IgG) has evolved over time. This study aims to evaluate the analytical performance of Alinity-i chemiluminescence immunoassays in detecting specific anti-HSV-1 and HSV-2 IgG.
Methods
A retrospective analysis was conducted on 157 serum samples collected from 155 patients between June 2023 and July 2024. Three assays were compared: Alinity® HSV-1 and HSV-2 IgG (Abbott), Liaison® HSV-1 and HSV-2 Type Specific IgG (Diasorin), and BioPlex® 2200 HSV-1 & HSV-2 IgG (Bio-Rad). Results were interpreted based on index values. The Anti-HSV-1/HSV-2-gG2 EUROLINE Western blot was used to provide definitive conclusions in cases of discordant results.
Results
The sensitivities and specificities of the Alinity-i assays were respectively 98 % and 100 % for HSV-1 IgG and 92 % and 98 % for HSV-2 IgG. The interpretation concordance among the three assays was high with Cohen's kappa values ranging from 0.82 to 0.90. Of the 27 discordant samples, Western-blot analysis identified false negatives as follows: 2 and 14 for Liaison, 3 and 5 for Alinity-i, and 2 and 0 for BioPlex, for HSV-1 and HSV-2 IgG respectively. Additionally, Western Blot revealed false positives in 3 Liaison and 1 BioPlex sample for HSV-1, and in 1 Liaison and 2 Alinity-i samples for HSV-2.
Conclusion
The Alinity-i HSV-1 and HSV-2 IgG serology demonstrated excellent sensitivities and specificities compared to Liaison and BioPlex assays. These findings underline the efficacy of Alinity-i in clinical diagnostics, suggesting it as a reliable tool for HSV-1 and HSV-2 antibody detection in diverse patient populations.
{"title":"Evaluation of the analytical performances of the Alinity-i HSV-1 IgG and HSV-2 IgG chemiluminescent immunoassays","authors":"Joachim Bourdin , Maud Salmona , Nadhira Fidouh , Sébastien Fouéré , Jérôme LeGoff , Sarah Maylin","doi":"10.1016/j.jcv.2025.105776","DOIUrl":"10.1016/j.jcv.2025.105776","url":null,"abstract":"<div><h3>Background</h3><div>The landscape of diagnostic assays for detecting herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) antibodies (IgG) has evolved over time. This study aims to evaluate the analytical performance of Alinity-i chemiluminescence immunoassays in detecting specific anti-HSV-1 and HSV-2 IgG.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on 157 serum samples collected from 155 patients between June 2023 and July 2024. Three assays were compared: Alinity® HSV-1 and HSV-2 IgG (Abbott), Liaison® HSV-1 and HSV-2 Type Specific IgG (Diasorin), and BioPlex® 2200 HSV-1 & HSV-2 IgG (Bio-Rad). Results were interpreted based on index values. The Anti-HSV-1/HSV-2-gG2 EUROLINE Western blot was used to provide definitive conclusions in cases of discordant results.</div></div><div><h3>Results</h3><div>The sensitivities and specificities of the Alinity-i assays were respectively 98 % and 100 % for HSV-1 IgG and 92 % and 98 % for HSV-2 IgG. The interpretation concordance among the three assays was high with Cohen's kappa values ranging from 0.82 to 0.90. Of the 27 discordant samples, Western-blot analysis identified false negatives as follows: 2 and 14 for Liaison, 3 and 5 for Alinity-i, and 2 and 0 for BioPlex, for HSV-1 and HSV-2 IgG respectively. Additionally, Western Blot revealed false positives in 3 Liaison and 1 BioPlex sample for HSV-1, and in 1 Liaison and 2 Alinity-i samples for HSV-2.</div></div><div><h3>Conclusion</h3><div>The Alinity-i HSV-1 and HSV-2 IgG serology demonstrated excellent sensitivities and specificities compared to Liaison and BioPlex assays. These findings underline the efficacy of Alinity-i in clinical diagnostics, suggesting it as a reliable tool for HSV-1 and HSV-2 antibody detection in diverse patient populations.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105776"},"PeriodicalIF":4.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563361","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 : 2025-03-06DOI: 10.1016/j.jcv.2025.105777
Mengying Gao , Lin Zhao , Qing Dong , Xiaofei Zhang , Lianfeng Li , Di Zhao , Qi Zhou , Yanli Xu , Peiyu Zhen , Shan Lu , Jiaqi Zhao , Wenya Tian , Guoyao Zu , Shuo Zhou , Bingbing Gu , Xiaokun Li , Minling Xu , Wuchun Cao
Background
Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) represents a novel bunyavirus that poses significant public health challenges. As a key prognostic indicator of clinical outcome, the viral load determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is relatively inaccurate and incomparable across different studies. Digital PCR (dPCR) has recently proved to be a more ideal tool for viral load assessment.
Objective
To develop a dPCR-based S-segment-specific method for SFTSV viral load monitoring and evaluate its performance in clinical samples.
Study design
Specific dPCR was developed using primers/probes for the N region in the S segment of the SFTSV genome. The performance of dPCR was confirmed using serial dilutions of viral cultures, and dPCR viral load quantification was compared with the result of RT-qPCR in 166 suspected SFTS patients.
Results
DPCR demonstrated superior sensitivity with a detection limit of 190.5 copies/mL, high linearity, and good reproducibility. Six false negative samples were detected by dPCR among the 28 RT-qPCR negative samples. The correlation between RT-qPCR and dPCR was low at a low viral load level. Both dPCR and RT-qPCR were important risk factors for severity and mortality by the multivariate logistic regression analysis The accurate viral load based on dPCR has a strong predictive ability for patient outcomes and shows significant correlation with multiple host response markers.
Conclusion
The results suggest that dPCR is a highly sensitive alternative to the measurement of SFTSV and should be considered for clinical utilization in patients with suspected SFTS.
{"title":"Development and evaluation of the digital PCR-based method for clinical monitoring of viral loads during severe fever with thrombocytopenia syndrome virus infection","authors":"Mengying Gao , Lin Zhao , Qing Dong , Xiaofei Zhang , Lianfeng Li , Di Zhao , Qi Zhou , Yanli Xu , Peiyu Zhen , Shan Lu , Jiaqi Zhao , Wenya Tian , Guoyao Zu , Shuo Zhou , Bingbing Gu , Xiaokun Li , Minling Xu , Wuchun Cao","doi":"10.1016/j.jcv.2025.105777","DOIUrl":"10.1016/j.jcv.2025.105777","url":null,"abstract":"<div><h3>Background</h3><div>Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) represents a novel bunyavirus that poses significant public health challenges. As a key prognostic indicator of clinical outcome, the viral load determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is relatively inaccurate and incomparable across different studies. Digital PCR (dPCR) has recently proved to be a more ideal tool for viral load assessment.</div></div><div><h3>Objective</h3><div>To develop a dPCR-based S-segment-specific method for SFTSV viral load monitoring and evaluate its performance in clinical samples.</div></div><div><h3>Study design</h3><div>Specific dPCR was developed using primers/probes for the N region in the S segment of the SFTSV genome. The performance of dPCR was confirmed using serial dilutions of viral cultures, and dPCR viral load quantification was compared with the result of RT-qPCR in 166 suspected SFTS patients.</div></div><div><h3>Results</h3><div>DPCR demonstrated superior sensitivity with a detection limit of 190.5 copies/mL, high linearity, and good reproducibility. Six false negative samples were detected by dPCR among the 28 RT-qPCR negative samples. The correlation between RT-qPCR and dPCR was low at a low viral load level. Both dPCR and RT-qPCR were important risk factors for severity and mortality by the multivariate logistic regression analysis The accurate viral load based on dPCR has a strong predictive ability for patient outcomes and shows significant correlation with multiple host response markers.</div></div><div><h3>Conclusion</h3><div>The results suggest that dPCR is a highly sensitive alternative to the measurement of SFTSV and should be considered for clinical utilization in patients with suspected SFTS.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105777"},"PeriodicalIF":4.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579491","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 : 2025-02-17DOI: 10.1016/j.jcv.2025.105774
Anne Thierbach , Veronica Di Cristanziano , Kirsten A. Eberhardt , Martin Pirkl , Gertrud Steger , Eva Heger , Rolf Kaiser , Manuel Koch , Florian Klein , Dominic Rauschning , Jakob J. Malin
Background
Immunocompromised individuals, hemato-oncologic diseases or post-transplantation included, are, due to impaired immune response, at increased risk for severe and prolonged COVID-19. Observational Studies showed that SARS-CoV-2 RNAemia has been associated with poorer prognosis and higher disease severity.
Objective
The aim of this study was to investigate the occurrence of RNAemia and its association with anti-SARS-CoV-2 antibodies in immunocompromised COVID-19 patients. Risk factors for RNAemia were included in the analysis.
Study design
A retrospective study was conducted in 55 immunocompromised patients tested positive for SARS-CoV-2, who received treatment with monoclonal antibodies (mAb) between December 2021 and March 2022. Serological and virological tests were performed before mAb administration and clinical data were collected from electronic health records.
Results
Out of 55 patients, 35 % showed SARS-CoV-2 RNAemia. RNAemia was present in the 2 reported fatal cases. It was associated with negative testing for anti-receptor binding domain (RBD) IgG, anti-S2 domain of spike protein (S2) IgG and a lower leukocyte count. No association was found between previous COVID-19 vaccinations and the risk for RNAemia in immunocompromised patients.
Conclusion
The study underscores the importance of humoral response in controlling SARS-CoV-2 replication. RNAemia can serve as a potential biomarker for disease severity in immunocompromised individuals. Therefore, it should be considered in clinical settings for appropriate therapy decisions. Further research is needed to evaluate the pathophysiology and implications of RNAemia in immunodeficient patients with COVID-19.
{"title":"High rate of RNAemia and impaired immunity in patients with immunodeficiency in the vaccination era","authors":"Anne Thierbach , Veronica Di Cristanziano , Kirsten A. Eberhardt , Martin Pirkl , Gertrud Steger , Eva Heger , Rolf Kaiser , Manuel Koch , Florian Klein , Dominic Rauschning , Jakob J. Malin","doi":"10.1016/j.jcv.2025.105774","DOIUrl":"10.1016/j.jcv.2025.105774","url":null,"abstract":"<div><h3>Background</h3><div>Immunocompromised individuals, hemato-oncologic diseases or post-transplantation included, are, due to impaired immune response, at increased risk for severe and prolonged COVID-19. Observational Studies showed that SARS-CoV-2 RNAemia has been associated with poorer prognosis and higher disease severity.</div></div><div><h3>Objective</h3><div>The aim of this study was to investigate the occurrence of RNAemia and its association with anti-SARS-CoV-2 antibodies in immunocompromised COVID-19 patients. Risk factors for RNAemia were included in the analysis.</div></div><div><h3>Study design</h3><div>A retrospective study was conducted in 55 immunocompromised patients tested positive for SARS-CoV-2, who received treatment with monoclonal antibodies (mAb) between December 2021 and March 2022. Serological and virological tests were performed before mAb administration and clinical data were collected from electronic health records.</div></div><div><h3>Results</h3><div>Out of 55 patients, 35 % showed SARS-CoV-2 RNAemia. RNAemia was present in the 2 reported fatal cases. It was associated with negative testing for anti-receptor binding domain (RBD) IgG, anti-S2 domain of spike protein (S2) IgG and a lower leukocyte count. No association was found between previous COVID-19 vaccinations and the risk for RNAemia in immunocompromised patients.</div></div><div><h3>Conclusion</h3><div>The study underscores the importance of humoral response in controlling SARS-CoV-2 replication. RNAemia can serve as a potential biomarker for disease severity in immunocompromised individuals. Therefore, it should be considered in clinical settings for appropriate therapy decisions. Further research is needed to evaluate the pathophysiology and implications of RNAemia in immunodeficient patients with COVID-19.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105774"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1016/j.jcv.2025.105771
Mark Anderson , Lara Teodoro , Fiona Harley , Eduardo Almaraz , Ana Vallari , Carolyn Strobel , Barbara Harris , Todd V. Meyer , Nicaise Ndembi , Dora Mbanya , Linda James , Souleymane Mboup , Jean-Christophe Plantier , Gavin Cloherty , Mary Rodgers
Background
HIV displays exceptionally high virus diversity that can impact detection by diagnostic assays, which rely on sequence conservation.
Methods
We tested the m-PIMA HIV-1/2 Detect point-of-care (POC) assay (Abbott Rapid Diagnostics) against a diverse HIV panel of 340 serum/plasma specimens and diluted cultured virus isolates for which viral load (VL) and classified sequences were known, including HIV-1 groups M, N, O, P, Circulating Recombinant Forms (CRF), and Unique Recombinant Forms (URF), and HIV-2. An in silico inclusivity analysis of 53,503 HIV-1 and 68 HIV-2 sequences from NCBI was performed to predict performance of m-PIMA HIV-1/2 Detect against a broader range of circulating strains.
Results
m-PIMA HIV-1/2 Detect detected HIV in 329/340 (96.8 %) tested samples. The mean VL was 3.80 (2.09–6.14) log copies/mL. Among samples with HIV VL >4000 copies/mL (3.60 log copies/mL; m-PIMA HIV-1/2 Detect design sensitivity), 181/181 (100 %) were detected. Among samples with VL between 3.0 and 3.6 log copies/mL, m-PIMA HIV-1/2 Detect detected 93/96 (96.9 %), and 55/63 (87.3 %) samples with VL below 3.0 log copies/mL were detected. At least one member from each subtype/CRF and all URFs were detected. In silico analysis identified 2/53,503 (0.0037 %) HIV-1 (both group O) and 1/68 (1.47 %) HIV-2 (subtype F) sequences with target region mutations that decreased identity below a 90 % threshold.
Conclusions
The m-PIMA HIV-1/2 Detect assay detected each of the major circulating HIV strains, including rare divergent strains. In silico analysis predicted that m-PIMA HIV-1/2 Detect would detect the majority of HIV-1 and HIV-2 strains indicating that this assay can detect the full range of HIV viral diversity.
{"title":"Detection of diverse HIV strains by the m-PIMATM HIV-1/2 detect point-of-care assay","authors":"Mark Anderson , Lara Teodoro , Fiona Harley , Eduardo Almaraz , Ana Vallari , Carolyn Strobel , Barbara Harris , Todd V. Meyer , Nicaise Ndembi , Dora Mbanya , Linda James , Souleymane Mboup , Jean-Christophe Plantier , Gavin Cloherty , Mary Rodgers","doi":"10.1016/j.jcv.2025.105771","DOIUrl":"10.1016/j.jcv.2025.105771","url":null,"abstract":"<div><h3>Background</h3><div>HIV displays exceptionally high virus diversity that can impact detection by diagnostic assays, which rely on sequence conservation.</div></div><div><h3>Methods</h3><div>We tested the m-PIMA HIV-1/2 Detect point-of-care (POC) assay (Abbott Rapid Diagnostics) against a diverse HIV panel of 340 serum/plasma specimens and diluted cultured virus isolates for which viral load (VL) and classified sequences were known, including HIV-1 groups M, N, O, P, Circulating Recombinant Forms (CRF), and Unique Recombinant Forms (URF), and HIV-2. An <em>in silico</em> inclusivity analysis of 53,503 HIV-1 and 68 HIV-2 sequences from NCBI was performed to predict performance of m-PIMA HIV-1/2 Detect against a broader range of circulating strains.</div></div><div><h3>Results</h3><div>m-PIMA HIV-1/2 Detect detected HIV in 329/340 (96.8 %) tested samples. The mean VL was 3.80 (2.09–6.14) log copies/mL. Among samples with HIV VL >4000 copies/mL (3.60 log copies/mL; m-PIMA HIV-1/2 Detect design sensitivity), 181/181 (100 %) were detected. Among samples with VL between 3.0 and 3.6 log copies/mL, m-PIMA HIV-1/2 Detect detected 93/96 (96.9 %), and 55/63 (87.3 %) samples with VL below 3.0 log copies/mL were detected. At least one member from each subtype/CRF and all URFs were detected. <em>In silico</em> analysis identified 2/53,503 (0.0037 %) HIV-1 (both group O) and 1/68 (1.47 %) HIV-2 (subtype F) sequences with target region mutations that decreased identity below a 90 % threshold.</div></div><div><h3>Conclusions</h3><div>The m-PIMA HIV-1/2 Detect assay detected each of the major circulating HIV strains, including rare divergent strains. In silico analysis predicted that m-PIMA HIV-1/2 Detect would detect the majority of HIV-1 and HIV-2 strains indicating that this assay can detect the full range of HIV viral diversity.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"177 ","pages":"Article 105771"},"PeriodicalIF":4.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jcv.2024.105757
Kevin Brown , Sabine Ditrich , John Harris , Miren Iturriza , Cherry Kang , Marion Koopmans , Satu Kurkela , Ben Lopman , Mick Mulders , Sarah O'Brien , Jan Vinjé , Hubert Niesters
{"title":"In memoriam David Brown, December 2024","authors":"Kevin Brown , Sabine Ditrich , John Harris , Miren Iturriza , Cherry Kang , Marion Koopmans , Satu Kurkela , Ben Lopman , Mick Mulders , Sarah O'Brien , Jan Vinjé , Hubert Niesters","doi":"10.1016/j.jcv.2024.105757","DOIUrl":"10.1016/j.jcv.2024.105757","url":null,"abstract":"","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"176 ","pages":"Article 105757"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379219","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 : 2025-02-01DOI: 10.1016/j.jcv.2024.105756
Tatiana M. Lanzieri , A. Chantal Caviness , Jill J. Williams , Gail Demmler-Harrison , the Houston Congenital Cytomegalovirus Longitudinal Study Group
Background
Cytomegalovirus (CMV) infection in children is associated with prolonged viral excretion in urine and saliva. This study characterizes CMV urinary excretion in children with congenital (cCMV) and postnatally acquired CMV infection.
Methods
Children with virologically confirmed cCMV (75 symptomatic and 105 asymptomatic at birth) and 51 children without cCMV were followed through median 11, 18 and 17 years of age, respectively. In children with cCMV, duration of CMV excretion was defined as uninterrupted positive results from initial to last positive culture, and recurrent CMV excretion as ≥1 positive following >1 negative result. CMV urinary excretion in children without cCMV was defined as resulting from postnatally acquired CMV infection.
Results
Mean duration of persistent CMV urinary excretion in children with cCMV was 1.9 (maximum 8.7) years for symptomatic and 2.8 (maximum 9.8) years for asymptomatic children (P = 0.011). Mean duration of CMV excretion was not statistically different for 17 symptomatic children treated with ganciclovir (2.4 years) compared with 58 untreated (1.8 years); P = 0.356. Recurrent excretion occurred in 19 (25 %) symptomatic and 21 (20 %) asymptomatic children, at mean age 4.0 and 6.2 years, respectively (P = 0.084). In 16 (31 %) children with postnatally acquired CMV infection, CMV urinary excretion began at mean age 1.8 (range 0.3–7.3) years.
Conclusions
Both symptomatic and asymptomatic cCMV were associated with persistent long-term CMV excretion in urine, which was significantly longer in asymptomatic cCMV and not influenced by ganciclovir treatment in symptomatic cCMV. CMV urinary excretion was common in young children without cCMV, suggesting rapid CMV acquisition in childhood.
{"title":"Cytomegalovirus urinary excretion in children with congenital and postnatally acquired infection","authors":"Tatiana M. Lanzieri , A. Chantal Caviness , Jill J. Williams , Gail Demmler-Harrison , the Houston Congenital Cytomegalovirus Longitudinal Study Group","doi":"10.1016/j.jcv.2024.105756","DOIUrl":"10.1016/j.jcv.2024.105756","url":null,"abstract":"<div><h3>Background</h3><div>Cytomegalovirus (CMV) infection in children is associated with prolonged viral excretion in urine and saliva. This study characterizes CMV urinary excretion in children with congenital (cCMV) and postnatally acquired CMV infection.</div></div><div><h3>Methods</h3><div>Children with virologically confirmed cCMV (75 symptomatic and 105 asymptomatic at birth) and 51 children without cCMV were followed through median 11, 18 and 17 years of age, respectively. In children with cCMV, duration of CMV excretion was defined as uninterrupted positive results from initial to last positive culture, and recurrent CMV excretion as ≥1 positive following >1 negative result. CMV urinary excretion in children without cCMV was defined as resulting from postnatally acquired CMV infection.</div></div><div><h3>Results</h3><div>Mean duration of persistent CMV urinary excretion in children with cCMV was 1.9 (maximum 8.7) years for symptomatic and 2.8 (maximum 9.8) years for asymptomatic children (<em>P</em> = 0.011). Mean duration of CMV excretion was not statistically different for 17 symptomatic children treated with ganciclovir (2.4 years) compared with 58 untreated (1.8 years); <em>P</em> = 0.356. Recurrent excretion occurred in 19 (25 %) symptomatic and 21 (20 %) asymptomatic children, at mean age 4.0 and 6.2 years, respectively (<em>P</em> = 0.084). In 16 (31 %) children with postnatally acquired CMV infection, CMV urinary excretion began at mean age 1.8 (range 0.3–7.3) years.</div></div><div><h3>Conclusions</h3><div>Both symptomatic and asymptomatic cCMV were associated with persistent long-term CMV excretion in urine, which was significantly longer in asymptomatic cCMV and not influenced by ganciclovir treatment in symptomatic cCMV. CMV urinary excretion was common in young children without cCMV, suggesting rapid CMV acquisition in childhood.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"176 ","pages":"Article 105756"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791864","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}
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