Pub Date : 2024-09-30DOI: 10.1016/j.jinf.2024.106289
Ying Liu , Daojun Yu , Kaixuan Wang , Qing Ye
Pertussis (or whooping cough) is a highly infectious acute respiratory disease primarily caused by Bordetella pertussis, which is also one of the most important causes of infant death worldwide. The widespread use of vaccines has greatly reduced the morbidity and mortality of pertussis. However, since the 1980s, in a number of countries with high vaccine coverage, the incidence of pertussis has risen again after remaining low for many years, with outbreaks even occurring in some areas. The peak onset of pertussis is shifting from infancy to adolescence, and adolescence is becoming the main source of infection for infants. Despite the increasing incidence of pertussis, serological findings suggest that the true prevalence of the disease may be significantly underestimated. Therefore, in this narrative review, we summarize the pathogenic process and immune characteristics of bacteria, the diagnosis and treatment of diseases, as well as vaccination and prevalence of pertussis at home and abroad, and attempt to analyze the causes and influencing factors of pertussis resurgence and summarize some prevention and control strategies to assist in improving the understanding of pertussis and preventing unexpected outbreaks.
{"title":"Global resurgence of pertussis: A perspective from China","authors":"Ying Liu , Daojun Yu , Kaixuan Wang , Qing Ye","doi":"10.1016/j.jinf.2024.106289","DOIUrl":"10.1016/j.jinf.2024.106289","url":null,"abstract":"<div><div>Pertussis (or whooping cough) is a highly infectious acute respiratory disease primarily caused by <em>Bordetella pertussis</em>, which is also one of the most important causes of infant death worldwide. The widespread use of vaccines has greatly reduced the morbidity and mortality of pertussis. However, since the 1980s, in a number of countries with high vaccine coverage, the incidence of pertussis has risen again after remaining low for many years, with outbreaks even occurring in some areas. The peak onset of pertussis is shifting from infancy to adolescence, and adolescence is becoming the main source of infection for infants. Despite the increasing incidence of pertussis, serological findings suggest that the true prevalence of the disease may be significantly underestimated. Therefore, in this narrative review, we summarize the pathogenic process and immune characteristics of bacteria, the diagnosis and treatment of diseases, as well as vaccination and prevalence of pertussis at home and abroad, and attempt to analyze the causes and influencing factors of pertussis resurgence and summarize some prevention and control strategies to assist in improving the understanding of pertussis and preventing unexpected outbreaks.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106289"},"PeriodicalIF":14.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.jinf.2024.106300
Muhammed D. Aksu , Tijmen van der Ent , Zhenhua Zhang , Anca L. Riza , Aline H. de Nooijer , Isis Ricaño-Ponce , Nico Janssen , Job J. Engel , Ioana Streata , Helga Dijkstra , Heidi Lemmers , Inge Grondman , Valerie A.C.M. Koeken , Eleni Antoniadou , Nikolaos Antonakos , Frank L. van de Veerdonk , Yang Li , Evangelos J. Giamarellos-Bourboulis , Mihai G. Netea , Athanasios Ziogas
Objectives
IL-1α/β and TNF are closely linked to the pathology of severe COVID-19 and sepsis. The soluble forms of their receptors, functioning as decoy receptors, exhibit inhibitory effects. However, little is known about their regulation in severe bacterial and viral infections, which we aimed to investigate in this study.
Methods
The circulating soluble receptors of TNF (sTNFR1 and sTNFR2) and IL-1α/β (sIL-1R1, sIL-1R2) were evaluated in the plasma of patients with COVID-19, severe bacterial infections, and sepsis and compared with healthy controls. Additionally, IL1R1, IL1R2, TNFRSF1A, and TNFRSF1B expression was evaluated at the single cell level in PBMCs derived from COVID-19 or sepsis patients.
Results
Plasma concentrations of sIL-1R1, sTNFR1, and sTNFR2 were significantly higher in COVID-19 patients compared to healthy subjects. Notably, sIL-1R1 levels were particularly elevated in ICU COVID-19 patients, and transcriptome analysis indicated heightened IL1R1 expression in PBMCs from severe COVID-19 patients. In severe bacterial infections, only sTNFR1 and sTNFR2 exhibited increased levels compared to healthy controls. Sepsis patients had decreased sIL-1R1 plasma concentrations but elevated sIL-1R2, sTNFR1, and sTNFR2 levels compared to healthy individuals, reflecting the heightened expression due to the increased numbers of monocytes present in sepsis. Finally, elevated concentrations of sIL-1R2, sTNFR1, and sTNFR2 were moderately associated with reduced 28-day survival in sepsis patients.
Conclusion
Our study reveals distinct regulation of plasma concentrations of soluble IL-1 receptors in COVID-19 and sepsis. Moreover, soluble TNF receptors 1 and 2 consistently rise in all conditions and show a positive correlation with disease severity in sepsis.
{"title":"Regulation of plasma soluble receptors of TNF and IL-1 in patients with COVID-19 differs from that observed in sepsis","authors":"Muhammed D. Aksu , Tijmen van der Ent , Zhenhua Zhang , Anca L. Riza , Aline H. de Nooijer , Isis Ricaño-Ponce , Nico Janssen , Job J. Engel , Ioana Streata , Helga Dijkstra , Heidi Lemmers , Inge Grondman , Valerie A.C.M. Koeken , Eleni Antoniadou , Nikolaos Antonakos , Frank L. van de Veerdonk , Yang Li , Evangelos J. Giamarellos-Bourboulis , Mihai G. Netea , Athanasios Ziogas","doi":"10.1016/j.jinf.2024.106300","DOIUrl":"10.1016/j.jinf.2024.106300","url":null,"abstract":"<div><h3>Objectives</h3><div>IL-1α/β and TNF are closely linked to the pathology of severe COVID-19 and sepsis. The soluble forms of their receptors, functioning as decoy receptors, exhibit inhibitory effects. However, little is known about their regulation in severe bacterial and viral infections, which we aimed to investigate in this study.</div></div><div><h3>Methods</h3><div>The circulating soluble receptors of TNF (sTNFR1 and sTNFR2) and IL-1α/β (sIL-1R1, sIL-1R2) were evaluated in the plasma of patients with COVID-19, severe bacterial infections, and sepsis and compared with healthy controls. Additionally, <em>IL1R1</em>, <em>IL1R2</em>, <em>TNFRSF1A</em>, and <em>TNFRSF1B</em> expression was evaluated at the single cell level in PBMCs derived from COVID-19 or sepsis patients.</div></div><div><h3>Results</h3><div>Plasma concentrations of sIL-1R1, sTNFR1, and sTNFR2 were significantly higher in COVID-19 patients compared to healthy subjects. Notably, sIL-1R1 levels were particularly elevated in ICU COVID-19 patients, and transcriptome analysis indicated heightened <em>IL1R1</em> expression in PBMCs from severe COVID-19 patients. In severe bacterial infections, only sTNFR1 and sTNFR2 exhibited increased levels compared to healthy controls. Sepsis patients had decreased sIL-1R1 plasma concentrations but elevated sIL-1R2, sTNFR1, and sTNFR2 levels compared to healthy individuals, reflecting the heightened expression due to the increased numbers of monocytes present in sepsis. Finally, elevated concentrations of sIL-1R2, sTNFR1, and sTNFR2 were moderately associated with reduced 28-day survival in sepsis patients.</div></div><div><h3>Conclusion</h3><div>Our study reveals distinct regulation of plasma concentrations of soluble IL-1 receptors in COVID-19 and sepsis. Moreover, soluble TNF receptors 1 and 2 consistently rise in all conditions and show a positive correlation with disease severity in sepsis.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106300"},"PeriodicalIF":14.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.jinf.2024.106299
Z.T. Wolie , J.A. Roberts , Y.M. Wale , S. Unwin , K. McCarthy , F.B. Sime
Objective
To review the literature on parenteral carbapenems in OPAT and present comprehensive evidence on their safety, efficacy, and stability.
Methods
A systematic review following PRISMA guidelines was conducted through 17 January 2024, using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to find relevant articles.
Results
Ertapenem (1 g QD) in OPAT showed high clinical (81–97%) and microbiological (67–90.9%) success rates. Ertapenem (1 g QD) was also comparable to piperacillin/tazobactam (3.375 g every 6 h) for complicated skin infections and superior to cefazolin (2 g every 8 h) and oxacillin (2 g every 4–6 h) for various infections. Ertapenem monotherapy, once daily, achieved an 81% clinical cure rate for urinary tract infections. Additionally, subcutaneous ertapenem in OPAT showed outcomes comparable to parenteral routes. Meropenem continuous infusion (CI) may also be considered safe and effective in selected patient populations; however, its use in OPAT as a CI is limited due to stability concerns.
Conclusion
Parenteral carbapenems are effective, and well-tolerated OPAT treatment options; nonetheless, further studies are warranted to optimize the stability and/or dosing regimens of meropenem and enable its wider use.
目的回顾有关 OPAT 中肠外碳青霉烯类药物的文献，并提供有关其安全性、有效性和稳定性的全面证据：方法：使用 PubMed、Embase、Web of Science、Scopus 和 Cochrane 图书馆查找相关文章，按照 PRISMA 指南进行了系统性综述（截至 2024 年 1 月 17 日）：厄他培南（1 克 QD）在 OPAT 中的临床成功率（81%-97%）和微生物成功率（67%-90.9%）都很高。在治疗复杂性皮肤感染方面，厄他培南（1 克 QD）的疗效与哌拉西林/他唑巴坦（3.375 克，每 6 小时一次）相当；在治疗各种感染方面，厄他培南（1 克 QD）的疗效优于头孢唑啉（2 克，每 8 小时一次）和氧西林（2 克，每 4-6 小时一次）。厄他培南单药治疗尿路感染，每日一次，临床治愈率达 81%。此外，在 OPAT 中皮下注射厄他培南的疗效与肠外途径相当。美罗培南持续输注（CI）在特定患者群体中也被认为是安全有效的；但由于稳定性问题，其在 OPAT 中作为 CI 的使用受到了限制：结论：肠外碳青霉烯类是有效且耐受性良好的 OPAT 治疗选择；然而，还需要进一步研究以优化美罗培南的稳定性和/或给药方案，使其得到更广泛的应用。
{"title":"Outpatient parenteral antimicrobial therapy with carbapenems: A systematic review","authors":"Z.T. Wolie , J.A. Roberts , Y.M. Wale , S. Unwin , K. McCarthy , F.B. Sime","doi":"10.1016/j.jinf.2024.106299","DOIUrl":"10.1016/j.jinf.2024.106299","url":null,"abstract":"<div><h3>Objective</h3><div>To review the literature on parenteral carbapenems in OPAT and present comprehensive evidence on their safety, efficacy, and stability.</div></div><div><h3>Methods</h3><div>A systematic review following PRISMA guidelines was conducted through 17 January 2024, using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to find relevant articles.</div></div><div><h3>Results</h3><div>Ertapenem (1 g QD) in OPAT showed high clinical (81–97%) and microbiological (67–90.9%) success rates. Ertapenem (1 g QD) was also comparable to piperacillin/tazobactam (3.375 g every 6 h) for complicated skin infections and superior to cefazolin (2 g every 8 h) and oxacillin (2 g every 4–6 h) for various infections. Ertapenem monotherapy, once daily, achieved an 81% clinical cure rate for urinary tract infections. Additionally, subcutaneous ertapenem in OPAT showed outcomes comparable to parenteral routes. Meropenem continuous infusion (CI) may also be considered safe and effective in selected patient populations; however, its use in OPAT as a CI is limited due to stability concerns.</div></div><div><h3>Conclusion</h3><div>Parenteral carbapenems are effective, and well-tolerated OPAT treatment options; nonetheless, further studies are warranted to optimize the stability and/or dosing regimens of meropenem and enable its wider use.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106299"},"PeriodicalIF":14.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-29DOI: 10.1016/j.jinf.2024.106297
Ankush Dehlia, Mark A. Guthridge
Objectives
Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.
Methods
Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.
Results
We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%−60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.
Conclusions
Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardised diagnosis, management and the recruitment for clinical studies in the future.
{"title":"The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis","authors":"Ankush Dehlia, Mark A. Guthridge","doi":"10.1016/j.jinf.2024.106297","DOIUrl":"10.1016/j.jinf.2024.106297","url":null,"abstract":"<div><h3>Objectives</h3><div>Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.</div></div><div><h3>Methods</h3><div>Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.</div></div><div><h3>Results</h3><div>We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%−60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.</div></div><div><h3>Conclusions</h3><div>Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardised diagnosis, management and the recruitment for clinical studies in the future.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106297"},"PeriodicalIF":14.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.jinf.2024.106293
Peter D. Kirwan , Sarah Foulkes , Katie Munro , Dominic Sparkes , Jasleen Singh , Amanda Henry , Angela Dunne , Jean Timeyin , Sophie Russell , Jameel Khawam , Debbie Blick , Ashley D. Otter , Nipunadi Hettiarachchi , Michelle D. Cairns , Christopher H. Jackson , Shaun Seaman , Colin S. Brown , SIREN Study Group , Ana Atti , Jasmin Islam , Susan Hopkins
Objectives
Bivalent original/BA.4–5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in the autumn of 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation.
Methods
Between October 2023 to March 2024, 2867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection.
Results
Half of the participants (1422) received a booster during October 2023 (280 bivalent, 1142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (−55.4 to 53.6%) at 0–2 months and 4.2% (−46.4 to 37.3%) at 2–4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0–2 months, and 24.1% (−0.7 to 42.9%) at 2–4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection.
Conclusions
Monovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations that target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs.
{"title":"Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024","authors":"Peter D. Kirwan , Sarah Foulkes , Katie Munro , Dominic Sparkes , Jasleen Singh , Amanda Henry , Angela Dunne , Jean Timeyin , Sophie Russell , Jameel Khawam , Debbie Blick , Ashley D. Otter , Nipunadi Hettiarachchi , Michelle D. Cairns , Christopher H. Jackson , Shaun Seaman , Colin S. Brown , SIREN Study Group , Ana Atti , Jasmin Islam , Susan Hopkins","doi":"10.1016/j.jinf.2024.106293","DOIUrl":"10.1016/j.jinf.2024.106293","url":null,"abstract":"<div><h3>Objectives</h3><div>Bivalent original/BA.4–5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in the autumn of 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation.</div></div><div><h3>Methods</h3><div>Between October 2023 to March 2024, 2867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection.</div></div><div><h3>Results</h3><div>Half of the participants (1422) received a booster during October 2023 (280 bivalent, 1142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (−55.4 to 53.6%) at 0–2 months and 4.2% (−46.4 to 37.3%) at 2–4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0–2 months, and 24.1% (−0.7 to 42.9%) at 2–4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection.</div></div><div><h3>Conclusions</h3><div>Monovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations that target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106293"},"PeriodicalIF":14.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.jinf.2024.106295
Linda Petrone , Daniela Peruzzu , Anna Maria Gerarda Altera , Andrea Salmi , Valentina Vanini , Gilda Cuzzi , Andrea Coppola , Valeria Mellini , Gina Gualano , Fabrizio Palmieri , Sudhasini Panda , Bjoern Peters , Alessandro Sette , Cecilia Sofie Lindestam Arlehamn , Delia Goletti
Background
Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the Mycobacterium tuberculosis (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.
Methods
In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay.
Results
ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p < 0.0001) and decreases during TB therapy (p = 0.0002). Flow cytometry confirms that ATB116-specific CD4+ T-cell response associated with Mtb regardless of infection/disease (p < 0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p = 0.016; p = 0.0242, respectively). CD4+ T cell-specific response decreases after TB therapy completion. The antigen-specific CD8+ T-cell response mirrors the CD4+ response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.
Conclusion
We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design.
背景：确定阶段特异性抗原对于开发结核病（TB）诊断和疫苗至关重要。在一个结核病低流行的国家，我们研究了结核分枝杆菌（Mtb）特异性免疫反应的特征，该免疫反应与结核病相关：在这项前瞻性观察横断面研究中，我们招募了健康供体（HD）、结核病患者和结核感染者（TBI）在基线和治疗结束时进行研究。用酶联免疫吸附试验、流式细胞术和多重检测法鉴定了多肽池刺激全血后的 T 细胞反应：结果：无论感染/患病情况如何，ATB116 特异性 IFN-γ 反应（通过酶联免疫吸附试验）都与 Mtb 显著相关（p+ T 细胞反应与 Mtb 相关，无论感染/患病情况如何（p+ T 细胞特异性反应在结核病治疗完成后下降）。抗原特异性 CD8+ T 细胞反应反映了 CD4+ 反应。最后，多重检测分析表明，ATB116 在结核病和创伤性脑损伤中都能诱导多种免疫因子：我们描述了结核病治疗对 Mtb 多肽池免疫反应的调节。这些结果对于我们了解结核病的免疫发病机制和疫苗设计非常重要：在本研究中生成和/或分析的原始数据将在 INMI 机构资料库（rawdata.inmi.it）中提供，但需注册。从按发表年份排序的文章列表中选择感兴趣的文章，即可找到相关数据。访问数据无需付费。如果应用程序出现故障，可直接通过电子邮件将请求发送至 biblioteca@inmi.it。
{"title":"Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection","authors":"Linda Petrone , Daniela Peruzzu , Anna Maria Gerarda Altera , Andrea Salmi , Valentina Vanini , Gilda Cuzzi , Andrea Coppola , Valeria Mellini , Gina Gualano , Fabrizio Palmieri , Sudhasini Panda , Bjoern Peters , Alessandro Sette , Cecilia Sofie Lindestam Arlehamn , Delia Goletti","doi":"10.1016/j.jinf.2024.106295","DOIUrl":"10.1016/j.jinf.2024.106295","url":null,"abstract":"<div><h3>Background</h3><div>Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the <em>Mycobacterium tuberculosis</em> (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.</div></div><div><h3>Methods</h3><div>In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay.</div></div><div><h3>Results</h3><div>ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p < 0.0001) and decreases during TB therapy (p = 0.0002). Flow cytometry confirms that ATB116-specific CD4<sup>+</sup> T-cell response associated with Mtb regardless of infection/disease (p < 0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p = 0.016; p = 0.0242, respectively). CD4<sup>+</sup> T cell-specific response decreases after TB therapy completion. The antigen-specific CD8<sup>+</sup> T-cell response mirrors the CD4<sup>+</sup> response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.</div></div><div><h3>Conclusion</h3><div>We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106295"},"PeriodicalIF":14.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.jinf.2024.106285
Chijioke Bennett , Zaheer Hoosain , Anthonet Koen , Umesh Lalloo , Cheryl Louw , Vongane Maluleke , Faeezah Patel , Gabriella Benade , Esme Louise Venter , Shirley Galbiati , Vivek Shinde , Shabir A. Madhi , on behalf of the Study 2019nCoV-505 Investigators Group
Background
Response data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status.
Methods
This phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18–65 years. PLWH were randomised 1:1:1 to receive NVX-CoV2373 on day 0 (D0) and either D21 (2-DoseD0/D21) or D70 (2-DoseD0/D70), or on D0, D21, and D70 (3-Dose). HIV-uninfected participants were randomised 1:1 to each 2-Dose regimen. PLWH were stratified into well-controlled and less–well-controlled subgroups. The primary immunologic endpoint included serum IgG and neutralising antibody responses (per geometric mean fold rise [GMFR] in titre and seroconversion rate) to ancestral SARS-CoV-2 at D35 (2-DoseD0/D21) and D84 (2-DoseD0/D70 and 3-Dose). The primary safety endpoints were participants with an unsolicited adverse event through D84, at D120, and at D180, or reactogenicity ≤7 days post-vaccination.
Results
Of 288 PLWH, 98, 96, and 94 were randomised into the 2-DoseD0/D21, 2-DoseD0/D70, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-DoseD0/D21 (n = 47) or 2-DoseD0/D70 (n = 49) regimens. Most (>85%) of the population were SARS-CoV-2 positive at baseline. Ancestral anti-spike IgG GMFRs in PLWH and HIV-uninfected participants, respectively, were 12·4 and 12·9 (D35) and 12·2 and 13·6 (D84). Comparable outcomes occurred across dosing regimens and in well-controlled and less–well-controlled PLWH. Microneutralization GMFRs at D84 in PLWH and HIV-uninfected participants, respectively, were: 6·9 and 10·1 (2-DoseD0/D21), 11·0 and 11·3 (2-DoseD0/D70), and 17·2 (PLWH 3-Dose). Antibody responses against BA.1 trended similar to those against the ancestral virus. Safety outcomes were comparable among PLWH and HIV-uninfected participants.
Conclusion
This study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals.
{"title":"Immunogenicity and safety of SARS-CoV-2 recombinant spike protein vaccine in South African people living with and without HIV-1 infection: A phase 2 randomised trial","authors":"Chijioke Bennett , Zaheer Hoosain , Anthonet Koen , Umesh Lalloo , Cheryl Louw , Vongane Maluleke , Faeezah Patel , Gabriella Benade , Esme Louise Venter , Shirley Galbiati , Vivek Shinde , Shabir A. Madhi , on behalf of the Study 2019nCoV-505 Investigators Group","doi":"10.1016/j.jinf.2024.106285","DOIUrl":"10.1016/j.jinf.2024.106285","url":null,"abstract":"<div><h3>Background</h3><div>Response data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status.</div></div><div><h3>Methods</h3><div>This phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18–65 years. PLWH were randomised 1:1:1 to receive NVX-CoV2373 on day 0 (D0) and either D21 (2-Dose<sub>D0/D21</sub>) or D70 (2-Dose<sub>D0/D70</sub>), or on D0, D21, and D70 (3-Dose). HIV-uninfected participants were randomised 1:1 to each 2-Dose regimen. PLWH were stratified into well-controlled and less–well-controlled subgroups. The primary immunologic endpoint included serum IgG and neutralising antibody responses (per geometric mean fold rise [GMFR] in titre and seroconversion rate) to ancestral SARS-CoV-2 at D35 (2-Dose<sub>D0/D21</sub>) and D84 (2-Dose<sub>D0/D70</sub> and 3-Dose). The primary safety endpoints were participants with an unsolicited adverse event through D84, at D120, and at D180, or reactogenicity ≤7 days post-vaccination.</div></div><div><h3>Results</h3><div>Of 288 PLWH, 98, 96, and 94 were randomised into the 2-Dose<sub>D0/D21</sub>, 2-Dose<sub>D0/D70</sub>, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-Dose<sub>D0/D21</sub> (n = 47) or 2-Dose<sub>D0/D70</sub> (n = 49) regimens. Most (>85%) of the population were SARS-CoV-2 positive at baseline. Ancestral anti-spike IgG GMFRs in PLWH and HIV-uninfected participants, respectively, were 12·4 and 12·9 (D35) and 12·2 and 13·6 (D84). Comparable outcomes occurred across dosing regimens and in well-controlled and less–well-controlled PLWH. Microneutralization GMFRs at D84 in PLWH and HIV-uninfected participants, respectively, were: 6·9 and 10·1 (2-Dose<sub>D0/D21</sub>), 11·0 and 11·3 (2-Dose<sub>D0/D70</sub>), and 17·2 (PLWH 3-Dose). Antibody responses against BA.1 trended similar to those against the ancestral virus. Safety outcomes were comparable among PLWH and HIV-uninfected participants.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106285"},"PeriodicalIF":14.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.jinf.2024.106296
Maisie Vollans , Julie Day , Susie Cant , Jordan Hood , A. Marm Kilpatrick , Laura D. Kramer , Alexander Vaux , Jolyon Medlock , Thomas Ward , Robert S. Paton
West Nile Virus (WNV) is a mosquito-borne pathogen that primarily infects birds. Infections can spillover to humans and cause a spectrum of clinical symptoms, including WNV neuroinvasive disease. The extrinsic incubation period (EIP) is the time taken for a mosquito to become infectious following the ingestion of an infected blood meal. Characterising how the EIP varies with temperature is an essential part of predicting the impact and transmission dynamics of WNV. We re-analyse existing experimental data using Bayesian time delay models, allowing us to account for variation in how quickly individual mosquitoes developed disseminated WNV infections. In these experiments, cohorts of Culex pipiens mosquitoes were infected with WNV and kept under different temperature conditions, being checked for disseminated infection at defined timepoints. We find that EIPs are best described with a Weibull distribution and become shorter log-linearly with temperature. Under 18°C, less than 1% of infected Cx. pipiens had a disseminated infection after 5 days, compared to 9.73% (95% CrI: 7.97 to 11.54) at 25°C and 42.20% (95% CrI: 38.32 to 46.60) at 30°C. In the hottest experimental temperature treatment (32°C), the EIP50 was estimated at 3.78 days (CrI: 3.42 to 4.15) compared to over 100 days in the coolest treatment (15°C). The variance of EIPs was found to be much larger at lower temperatures than higher temperatures, highlighting the importance of characterising the time delay distribution associated with the EIP. We additionally demonstrate a competitive advantage of WNV strain WN02 over NY99, where the former infects mosquitoes more quickly at colder temperatures than the latter. This research contributes crucial parameters to the WNV literature, providing essential insights for modellers and those planning interventions.
{"title":"Modelling the temperature dependent extrinsic incubation period of West Nile Virus using Bayesian time delay models","authors":"Maisie Vollans , Julie Day , Susie Cant , Jordan Hood , A. Marm Kilpatrick , Laura D. Kramer , Alexander Vaux , Jolyon Medlock , Thomas Ward , Robert S. Paton","doi":"10.1016/j.jinf.2024.106296","DOIUrl":"10.1016/j.jinf.2024.106296","url":null,"abstract":"<div><div>West Nile Virus (WNV) is a mosquito-borne pathogen that primarily infects birds. Infections can spillover to humans and cause a spectrum of clinical symptoms, including WNV neuroinvasive disease. The extrinsic incubation period (EIP) is the time taken for a mosquito to become infectious following the ingestion of an infected blood meal. Characterising how the EIP varies with temperature is an essential part of predicting the impact and transmission dynamics of WNV. We re-analyse existing experimental data using Bayesian time delay models, allowing us to account for variation in how quickly individual mosquitoes developed disseminated WNV infections. In these experiments, cohorts of <em>Culex pipiens</em> mosquitoes were infected with WNV and kept under different temperature conditions, being checked for disseminated infection at defined timepoints. We find that EIPs are best described with a Weibull distribution and become shorter log-linearly with temperature. Under 18°C, less than 1% of infected <em>Cx. pipiens</em> had a disseminated infection after 5 days, compared to 9.73% (95% CrI: 7.97 to 11.54) at 25°C and 42.20% (95% CrI: 38.32 to 46.60) at 30°C. In the hottest experimental temperature treatment (32°C), the EIP<sub>50</sub> was estimated at 3.78 days (CrI: 3.42 to 4.15) compared to over 100 days in the coolest treatment (15°C). The variance of EIPs was found to be much larger at lower temperatures than higher temperatures, highlighting the importance of characterising the time delay distribution associated with the EIP. We additionally demonstrate a competitive advantage of WNV strain WN02 over NY99, where the former infects mosquitoes more quickly at colder temperatures than the latter. This research contributes crucial parameters to the WNV literature, providing essential insights for modellers and those planning interventions.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106296"},"PeriodicalIF":14.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.jinf.2024.106294
Valentina Mazzotta , Fulvia Mazzaferri , Simone Lanini , Massimo Mirandola , Alessandro Cozzi Lepri , Alessandra Vergori , Alessia Savoldi , Andrea Santoro , Gaia Maccarrone , Ilaria Mastrorosa , Omar Simonetti , Federico De Zottis , Emanuele Nicastri , Giulia Rosini , Laura Rovigo , Lorenzo Tavernaro , Loredana Sarmati , Carlo Tascini , Enrico Girardi , Anna Maria Cattelan , Evelina Tacconelli
<div><h3>Background</h3><div>The clinical effectiveness of early therapies for mild-to-moderate COVID-19, comparing antivirals and monoclonal antibodies (mAbs) during the Omicron era, has not been conclusively assessed through a post-approval comparative trial. We present a pooled analysis of two randomized clinical trials conducted during Omicron waves.</div></div><div><h3>Methods</h3><div>The MANTICO2/MONET trial is a pooled analysis of two multicentric, independent, phase-4, three-arm, superiority, randomized, open-label trials. Nonhospitalized patients with early mild-to-moderate COVID-19 (≤5 days after symptoms’ onset) and at least one risk factor for disease progression were randomized 1:1:1 to receive 500 mg of intravenous sotrovimab (SOT) or 600 mg of intramuscular tixagevimab/cilgavimab (TGM/CGM) or oral 5-days course of nirmatrelvir/ritonavir (NMV/r) 300/100 mg BID. Primary outcome was COVID-19-related hospitalization or death within 29 days after randomization. Fisher’s exact test for pooled data and incidence of failure was reported as overall and by arm with respective 95% CI. Pairwise comparisons across the arms were conducted using unadjusted exact logistic regression. An analysis by means of a doubly robust marginal model using augmented inverse probability weighting (AIPW) was also conducted to estimate the potential outcomes (Pom) in each treatment group and their difference by the average treatment effect (ATE). Analysis of symptom persistence within 30 days after randomization was performed using a 2-level hierarchical mixed-effects logistic model with a random intercept at the patient’s level. Point estimates and 95% confidence intervals were adjusted for age and sex and calculated using ANOVA-like methods for the mixed effects logistic model. These trials are registered with the European Clinical Trials Database, EudraCT2021-002612-31 (MANTICO2) and EudraCT2021–004188-28 (MONET) and ClinicalTrials.gov, NCT05321394 (MANTICO2).</div></div><div><h3>Findings</h3><div>Between March 2022 and February 2023, 991 patients (SOT = 332, TGM/CGM = 327, NMV/r = 332) were enrolled in 15 Italian centers. The overall mean age was 66 years; 482 participants (48.80%) were male, and 856 were vaccinated with at least a primary course (86%). Among the 8/991 hospitalizations observed, one resulted in death. The overall estimate of failure was 0.81% (95%CI; 0.35–1.58%). The odds ratio (OR) for the primary outcome in the NMV/r arm compared to the TGM/CGM and SOT arms was 8.41 (95% CI 1.21 to infinity; p = 0.015) and 2.42 (95% CI 0.19 to infinity; p = 0.499), respectively. No significant difference was observed between SOT and TGM/CGM (OR 0.32; 95% CI 0.032–1.83; p = 0.174). Results were similar when we applied the marginal weighted model accounting for potential residual confounding bias. There was no evidence for a difference in the prevalence of symptoms between treatment groups, except for cough, which was higher in the SOT group compared to the
{"title":"Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves","authors":"Valentina Mazzotta , Fulvia Mazzaferri , Simone Lanini , Massimo Mirandola , Alessandro Cozzi Lepri , Alessandra Vergori , Alessia Savoldi , Andrea Santoro , Gaia Maccarrone , Ilaria Mastrorosa , Omar Simonetti , Federico De Zottis , Emanuele Nicastri , Giulia Rosini , Laura Rovigo , Lorenzo Tavernaro , Loredana Sarmati , Carlo Tascini , Enrico Girardi , Anna Maria Cattelan , Evelina Tacconelli","doi":"10.1016/j.jinf.2024.106294","DOIUrl":"10.1016/j.jinf.2024.106294","url":null,"abstract":"<div><h3>Background</h3><div>The clinical effectiveness of early therapies for mild-to-moderate COVID-19, comparing antivirals and monoclonal antibodies (mAbs) during the Omicron era, has not been conclusively assessed through a post-approval comparative trial. We present a pooled analysis of two randomized clinical trials conducted during Omicron waves.</div></div><div><h3>Methods</h3><div>The MANTICO2/MONET trial is a pooled analysis of two multicentric, independent, phase-4, three-arm, superiority, randomized, open-label trials. Nonhospitalized patients with early mild-to-moderate COVID-19 (≤5 days after symptoms’ onset) and at least one risk factor for disease progression were randomized 1:1:1 to receive 500 mg of intravenous sotrovimab (SOT) or 600 mg of intramuscular tixagevimab/cilgavimab (TGM/CGM) or oral 5-days course of nirmatrelvir/ritonavir (NMV/r) 300/100 mg BID. Primary outcome was COVID-19-related hospitalization or death within 29 days after randomization. Fisher’s exact test for pooled data and incidence of failure was reported as overall and by arm with respective 95% CI. Pairwise comparisons across the arms were conducted using unadjusted exact logistic regression. An analysis by means of a doubly robust marginal model using augmented inverse probability weighting (AIPW) was also conducted to estimate the potential outcomes (Pom) in each treatment group and their difference by the average treatment effect (ATE). Analysis of symptom persistence within 30 days after randomization was performed using a 2-level hierarchical mixed-effects logistic model with a random intercept at the patient’s level. Point estimates and 95% confidence intervals were adjusted for age and sex and calculated using ANOVA-like methods for the mixed effects logistic model. These trials are registered with the European Clinical Trials Database, EudraCT2021-002612-31 (MANTICO2) and EudraCT2021–004188-28 (MONET) and ClinicalTrials.gov, NCT05321394 (MANTICO2).</div></div><div><h3>Findings</h3><div>Between March 2022 and February 2023, 991 patients (SOT = 332, TGM/CGM = 327, NMV/r = 332) were enrolled in 15 Italian centers. The overall mean age was 66 years; 482 participants (48.80%) were male, and 856 were vaccinated with at least a primary course (86%). Among the 8/991 hospitalizations observed, one resulted in death. The overall estimate of failure was 0.81% (95%CI; 0.35–1.58%). The odds ratio (OR) for the primary outcome in the NMV/r arm compared to the TGM/CGM and SOT arms was 8.41 (95% CI 1.21 to infinity; p = 0.015) and 2.42 (95% CI 0.19 to infinity; p = 0.499), respectively. No significant difference was observed between SOT and TGM/CGM (OR 0.32; 95% CI 0.032–1.83; p = 0.174). Results were similar when we applied the marginal weighted model accounting for potential residual confounding bias. There was no evidence for a difference in the prevalence of symptoms between treatment groups, except for cough, which was higher in the SOT group compared to the ","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106294"},"PeriodicalIF":14.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.jinf.2024.106284
Xingwen Chen , John Balliew , Cici X. Bauer , Jennifer Deegan , Anna Gitter , Blake M. Hanson , Anthony W. Maresso , Michael J. Tisza , Catherine L. Troisi , Janelle Rios , Kristina D. Mena , Eric Boerwinkle , Fuqing Wu
Objectives
Rapid evolution of SARS-CoV-2 has resulted in the emergence of numerous variants, posing significant challenges to public health surveillance. Clinical genome sequencing, while valuable, has limitations in capturing the full epidemiological dynamics of circulating variants in the general population. This study aimed to monitor the SARS-CoV-2 variant community dynamics and evolution using receptor-binding domain (RBD) amplicon sequencing of wastewater samples.
Methods
We sequenced wastewater from El Paso, Texas, over 17 months, compared the sequencing data with clinical genome data, and performed biodiversity analysis to reveal SARS-CoV-2 variant dynamics and evolution.
Results
We identified 91 variants and observed waves of dominant variants transitioning from BA.2 to BA.2.12.1, BA.4&5, BQ.1, and XBB.1.5. Comparison with clinical genome sequencing data revealed earlier detection of variants and identification of unreported outbreaks. Our results also showed strong consistency with clinical data for dominant variants at the local, state, and national levels. Alpha diversity analyses revealed significant seasonal variations, with the highest diversity observed in winter. By segmenting the outbreak into lag, growth, stationary, and decline phases, we found higher variant diversity during the lag phase, likely due to lower inter-variant competition preceding outbreak growth.
Conclusions
Our findings underscore the importance of low transmission periods in facilitating rapid mutation and variant evolution. Our approach, integrating RBD amplicon sequencing with wastewater surveillance, demonstrates effectiveness in tracking viral evolution and understanding variant emergence, thus enhancing public health preparedness.
{"title":"Revealing patterns of SARS-CoV-2 variant emergence and evolution using RBD amplicon sequencing of wastewater","authors":"Xingwen Chen , John Balliew , Cici X. Bauer , Jennifer Deegan , Anna Gitter , Blake M. Hanson , Anthony W. Maresso , Michael J. Tisza , Catherine L. Troisi , Janelle Rios , Kristina D. Mena , Eric Boerwinkle , Fuqing Wu","doi":"10.1016/j.jinf.2024.106284","DOIUrl":"10.1016/j.jinf.2024.106284","url":null,"abstract":"<div><h3>Objectives</h3><div>Rapid evolution of SARS-CoV-2 has resulted in the emergence of numerous variants, posing significant challenges to public health surveillance. Clinical genome sequencing, while valuable, has limitations in capturing the full epidemiological dynamics of circulating variants in the general population. This study aimed to monitor the SARS-CoV-2 variant community dynamics and evolution using receptor-binding domain (RBD) amplicon sequencing of wastewater samples.</div></div><div><h3>Methods</h3><div>We sequenced wastewater from El Paso, Texas, over 17 months, compared the sequencing data with clinical genome data, and performed biodiversity analysis to reveal SARS-CoV-2 variant dynamics and evolution.</div></div><div><h3>Results</h3><div>We identified 91 variants and observed waves of dominant variants transitioning from BA.2 to BA.2.12.1, BA.4&5, BQ.1, and XBB.1.5. Comparison with clinical genome sequencing data revealed earlier detection of variants and identification of unreported outbreaks. Our results also showed strong consistency with clinical data for dominant variants at the local, state, and national levels. Alpha diversity analyses revealed significant seasonal variations, with the highest diversity observed in winter. By segmenting the outbreak into lag, growth, stationary, and decline phases, we found higher variant diversity during the lag phase, likely due to lower inter-variant competition preceding outbreak growth.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the importance of low transmission periods in facilitating rapid mutation and variant evolution. Our approach, integrating RBD amplicon sequencing with wastewater surveillance, demonstrates effectiveness in tracking viral evolution and understanding variant emergence, thus enhancing public health preparedness.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106284"},"PeriodicalIF":14.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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