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Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic: A randomised clinical trial 评估在 COVID-19 大流行期间接种卡介苗对老年人非特异性感染保护的效果:随机临床试验。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-17 DOI: 10.1016/j.jinf.2024.106319
Anne Marie Rosendahl Madsen , Lise Gehrt , Frederik Schaltz-Buchholzer , Sören Möller , Rikke Christiansen , Lars Schellerup , Lene Annette Norberg , Tyra Grove Krause , Sebastian Nielsen , Mette Bliddal , Peter Aaby , Christine Stabell Benn

Objectives

The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens.

Methods

Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI).

Results

The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78–1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75–1.26) or all-cause hospitalisations (1.10, 0.80–1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10–1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70–0.95) but not among those >75 years (1.14, 0.88–1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50–0.85).

Conclusion

BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination.

Trial registration

ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov.

Summary

In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.
目的:卡介苗(Bacillus Calmette-Guérin,BCG)可诱导非特异性保护,预防无关感染。我们测试了卡介苗对丹麦老年人感染风险的影响:单盲随机对照试验,包括 1,676 名年龄大于 65 岁的志愿者。参与者按 1:1 的比例随机接受卡介苗或安慰剂治疗,并随访 12 个月。主要结果是急性感染导致医疗接触。次要结果是经证实的 SARS-CoV-2 感染、自我报告的呼吸道症状和全因住院。数据采用 Cox 回归模型进行分析,估算出危险比(HR)和 95% 的置信区间(CI):卡介苗和安慰剂的急性感染发病率分别为每100人年52.1例和58.2例(HR=0.89,95% CI=0.78-1.02)。卡介苗对 SARS-CoV-2 感染(0.97,0.75-1.26)或全因住院(1.10,0.80-1.50)没有影响,但卡介苗与更多呼吸道症状(1.21,1.10-1.33)相关。卡介苗降低了 75 岁参与者的急性感染发病率(1.14,0.88-1.47)。在入组前接种过 COVID-19 疫苗的参与者中,卡介苗与较低的急性感染发病率相关(0.65,0.50-0.85):卡介苗总体上并未降低丹麦老年人的急性感染风险,但其效果因年龄组和接种 COVID-19 疫苗而异:试验注册:ClinicalTrials.gov(NCT04542330)和欧盟临床试验注册(EudraCT 编号 2020-003904-15)。摘要:在一项针对丹麦老年人的随机临床试验中,卡介苗接种并未降低急性感染的总体风险,但卡介苗接种可降低参与者的风险。
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引用次数: 0
Assessment of neutralizing antibody response as a correlate of protection against symptomatic SARS-CoV-2 infections after administration of two doses of the CoronaVac inactivated COVID-19 vaccine: A phase III randomized controlled trial 评估中和抗体反应作为接种两剂 CoronaVac COVID-19 灭活疫苗后对无症状 SARS-CoV-2 感染的保护作用的相关因素:III期随机对照试验。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-16 DOI: 10.1016/j.jinf.2024.106315
Xinhua Chen , Xing Meng , Qianhui Wu , Wey Wen Lim , Qianqian Xin , Benjamin J. Cowling , Weining Meng , Hongjie Yu , Dimas Tadeu Covasa

Background

The emergence of variants of concerns of SARS-CoV-2 highlights the need for comprehensively elucidating the correlates of protection for different COVID-19 vaccine types. Inactivated COVID-19 vaccines are currently amongst the most widely administered vaccines globally. However, investigations into the correlates of protection for inactivated COVID-19 vaccines are relatively rare.

Methods

Data from a phase III double-blind, randomized, placebo-controlled clinical trial (NCT0445659) that evaluated the efficacy and safety of the CoronaVac vaccine in healthcare professionals were utilized in this secondary analysis. Additionally, the correlation between neutralizing antibody levels measured by micro-cytopathic effect (CPE) neutralization assay and the occurrence of laboratory-confirmed infections was assessed using neutralizing antibodies measured in blood samples collected on day 28 after receiving two doses of the vaccine. Finally, the protective threshold required to provide 50% protection against symptomatic illness and virus infections was estimated.

Results

The risk of infection was negatively correlated with the levels of post-vaccination neutralizing antibodies measured on day 28 after the second dose. A neutralization titer of 30 (95% CI: 2–56) was predicted to provide 50% efficacy against symptomatic infection, whilst a titer of 42 (95% CI: 24–62) was predicted to provide 50% efficacy against total infection. Lastly, a neutralization titer of 247 (95% CI: 139–506) or higher was required to achieve 80% or higher protection against symptomatic infections.

Conclusions

The results highlight the value of neutralizing antibody response as a correlate of protection, which can be used to inform future vaccine development and implementation. Further studies of immune correlates of protection for other vaccines are warranted.
背景:令人担忧的 SARS-CoV-2 变异株的出现凸显了全面阐明不同 COVID-19 疫苗类型的保护相关性的必要性。COVID-19 灭活疫苗是目前全球接种最广泛的疫苗之一。然而,对 COVID-19 灭活疫苗保护相关性的调查却相对较少:本二次分析采用了一项 III 期双盲、随机、安慰剂对照临床试验(NCT0445659)的数据,该试验评估了 CoronaVac 疫苗对医护人员的有效性和安全性。此外,还利用接种两剂疫苗后第 28 天采集的血样中测得的中和抗体,评估了微小细胞病理效应 (CPE) 中和测定法测得的中和抗体水平与实验室确诊感染发生率之间的相关性。最后,还估算了对无症状疾病和病毒感染提供 50%保护所需的保护阈值:结果:感染风险与接种第二剂疫苗后第 28 天测得的接种后中和抗体水平呈负相关。预测中和滴度为 30(95% CI:2-56)时,对无症状感染的有效率为 50%,而滴度为 42(95% CI:24-62)时,对全部感染的有效率为 50%。最后,中和滴度达到247(95% CI:139-506)或更高,才能对无症状感染产生80%或更高的保护作用:结论:研究结果凸显了中和抗体反应作为保护相关因素的价值,可为未来疫苗的开发和实施提供参考。有必要进一步研究其他疫苗的免疫保护相关性。
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引用次数: 0
Mechanisms and implications of IgG4 responses to SARS-CoV-2 and other repeatedly administered vaccines IgG4 对 SARS-CoV-2 和其他重复接种疫苗的反应机制和影响。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-16 DOI: 10.1016/j.jinf.2024.106317
Anthony M. Marchese , Louis Fries , Hadi Beyhaghi , Muruga Vadivale , Mingzhu Zhu , Shane Cloney-Clark , Joyce S. Plested , Amy W. Chung , Lisa M. Dunkle , Raj Kalkeri
Vaccine-induced immunoglobulin G (IgG) profiles can vary with respect to the predominant subclasses that characterize the response. Among IgG subclasses, IgG4 is reported to have anti-inflammatory properties, but can also exhibit reduced capacity for virus neutralization and activation of Fc-dependent effector functions. Here, we review evidence that IgG4 subclass responses can be disproportionately increased in response to some types of vaccines targeting an array of diseases, including pertussis, HIV, malaria, and COVID-19. The basis for enhanced IgG4 induction by vaccines is poorly understood but may be associated with platform- or dose regimen–specific differences in antigen exposure and/or cytokine stimulation. The clinical implications of vaccine-induced IgG4 responses remain uncertain, though collective evidence suggests that proportional increases in IgG4 might reduce vaccine antigen-specific immunity. Additional work is needed to determine underlying mechanisms and to elucidate what role IgG4 may play in modifications of vaccine-induced immunity to disease.
疫苗诱导的免疫球蛋白 G (IgG) 可因反应的主要亚类而有所不同。据报道,在 IgG 亚类中,IgG4 具有抗炎特性,但也会表现出中和病毒和激活 Fc 依赖性效应器功能的能力下降。在此,我们回顾了一些证据,这些证据表明,在接种某些类型的疫苗时,IgG4 亚类的反应会不成比例地增加,这些疫苗针对的疾病包括百日咳、艾滋病、疟疾和 COVID-19。疫苗诱导 IgG4 增高的原因尚不清楚,但可能与抗原暴露和/或细胞因子刺激的平台或剂量方案特异性差异有关。疫苗诱导的 IgG4 反应对临床的影响仍不确定,但有综合证据表明,IgG4 的比例增加可能会降低疫苗抗原特异性免疫力。还需要做更多的工作来确定潜在的机制,并阐明 IgG4 在改变疫苗诱导的疾病免疫中可能扮演的角色。
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引用次数: 0
Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study 假体关节感染抑制性抗菌治疗的全球实践差异:一项横断面调查研究。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-15 DOI: 10.1016/j.jinf.2024.106316
Jaap L.J. Hanssen , Maaike G.J. Gademan , Marjan Wouthuyzen-Bakker , Joshua S. Davis , David Dewar , Laurens Manning , David Campbell , Joffrey van Prehn , Andy O. Miller , Robert J.P. van der Wal , Henrica M.J. van der Linden , Nicolás W. Cortés-Penfield , Alex Soriano , Mark G.J. de Boer , Henk Scheper

Objectives

To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI).

Methods

An online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups.

Results

Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months–3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%).

Conclusions

Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.
目的确定全球在使用抑制性抗菌疗法(SAT)治疗人工关节感染(PJI)方面的差异:方法: 设计了一项在线调查,以调查临床医生对 PJI 采用抑制性抗菌疗法的方法,包括适应症、首选抗菌药物、剂量、疗程和随访。调查对象为四个国际(骨与关节)感染学会和研究小组的成员:受访者包括来自 43 个不同国家的 330 名医生(204 名传染病专家、110 名骨科外科医生、23 名临床微生物学家)(欧洲 134 人,占 41%;大洋洲 112 人,占 34%;北美 51 人,占 16%;其他 33 人,占 10%;总回复率 20%)。在清创、抗生素和种植体保留(DAIR)或一期翻修后,38% 的北美受访者会经常或几乎总是启动 SAT,但只有 6% 的欧洲受访者和 7% 的大洋洲受访者会这样做。在北美洲,治疗葡萄球菌 PJI 的首选 SAT 是口服头孢菌素(39%)和四环素(31%);在欧洲,首选四环素(27%)和抗葡萄球菌青霉素(22%);在大洋洲,首选抗葡萄球菌青霉素(55%)。全球或各地区都没有针对革兰氏阴性 PJI 的首选 SAT 方案。在所有受访者中,从未降低过 SAT 的剂量(126 人,38%)、降低了特定抗生素的剂量(125 人,38%)或降低了所有抗生素的剂量(79 人,24%)。SAT 的处方持续时间为终身(43 人,占 13%)、固定持续时间(6 个月至 3 年不等)(104 人,占 32%)或未确定持续时间(154 人,占 47%):结论:PJI 中的 SAT 治疗方法具有很强的区域性,世界各地的医生对 SAT 的适应症、选择、剂量或持续时间没有达成共识。这反映了数据的匮乏,需要进行高质量的研究,以确定在治疗 PJI 患者时 SAT 的最佳使用方法。
{"title":"Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study","authors":"Jaap L.J. Hanssen ,&nbsp;Maaike G.J. Gademan ,&nbsp;Marjan Wouthuyzen-Bakker ,&nbsp;Joshua S. Davis ,&nbsp;David Dewar ,&nbsp;Laurens Manning ,&nbsp;David Campbell ,&nbsp;Joffrey van Prehn ,&nbsp;Andy O. Miller ,&nbsp;Robert J.P. van der Wal ,&nbsp;Henrica M.J. van der Linden ,&nbsp;Nicolás W. Cortés-Penfield ,&nbsp;Alex Soriano ,&nbsp;Mark G.J. de Boer ,&nbsp;Henk Scheper","doi":"10.1016/j.jinf.2024.106316","DOIUrl":"10.1016/j.jinf.2024.106316","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI).</div></div><div><h3>Methods</h3><div>An online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups.</div></div><div><h3>Results</h3><div>Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months–3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%).</div></div><div><h3>Conclusions</h3><div>Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106316"},"PeriodicalIF":14.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479500","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}
引用次数: 0
Duration of antimicrobial treatment for uncomplicated streptococcal bacteraemia: Another example of shorter is better 无并发症链球菌菌血症的抗菌治疗时间:时间越短越好的另一个例子
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-13 DOI: 10.1016/j.jinf.2024.106313
Nicolas Fourré , Virgile Zimmermann , Laurence Senn , Marion Aruanno , Benoit Guery , Matthaios Papadimitriou-Olivgeris

Objectives

Duration of treatment for uncomplicated streptococcal bacteraemia is unknown. The study aims to assess clinical outcomes of patients with uncomplicated streptococcal bacteraemia receiving a short course (5–10 days) of antimicrobial treatment compared to those receiving the traditional, longer duration (11–18 days).

Methods

This retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of uncomplicated streptococcal bacteraemia among adult patients from 2015 to 2023. Clinical failure was defined as mortality, recurrence of bacteraemia by the same streptococcal species and development in bone and joint infection within 120 days.

Results

During the study period, 336 episodes of uncomplicated streptococcal bacteraemia were included. The median duration of antimicrobial treatment was 10 days (interquartile range: 7–14); 184 (55%) and 152 (45%) episodes received a short (5–10 days) and long (11–18 days) duration of antimicrobial treatment, respectively. Forty-three (13%) episodes had clinical failure; 120-day mortality was 11% (36 episodes); recurrence of bacteraemia by the same streptococcal species was observed in 8 episodes (2%). No difference in clinical failure was observed between episodes receiving short and long courses of antimicrobial treatment (10% versus 16%; P 0.143). The Cox multivariable regression model found that a Charlson comorbidity index >4 (aHR 4.87, 95% CI 3.08–7.71), and septic shock (1.67, 1.04–2.67) were associated with clinical failure; a short course of antimicrobial treatment was not associated with clinical failure (0.90, 0.57–1.12).

Conclusions

This study has shown that a short duration of antimicrobial treatment for cases of streptococcal bacteraemia is effective and safe.
目的:无并发症链球菌菌血症的治疗时间尚不清楚。本研究旨在评估接受短疗程(5-10 天)抗菌药物治疗的无并发症链球菌菌血症患者与接受传统长疗程(11-18 天)抗菌药物治疗的患者的临床疗效。临床失败定义为死亡、同一链球菌菌血症复发以及在120天内出现骨关节感染。抗菌治疗的中位持续时间为 10 天(四分位数间距:7-14 天);分别有 184 例(55%)和 152 例(45%)患者接受了短期(5-10 天)和长期(11-18 天)抗菌治疗。43例(13%)临床治疗失败;120天死亡率为11%(36例);8例(2%)再次发生同一链球菌菌血症。接受短疗程和长疗程抗菌治疗的病例在临床失败率上没有差异(10% 对 16%;P 0.143)。Cox多变量回归模型发现,Charlson合并症指数>4(aHR 4.87,95% CI 3.08-7.71)和脓毒性休克(1.67,1.04-2.67)与临床失败有关;抗菌治疗疗程短与临床失败无关(0.90,0.57-1.12)。
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引用次数: 0
Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent 从乌克兰战争受害者体内分离出的耐潘生菌肺炎克雷伯氏菌具有高病毒性。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-11 DOI: 10.1016/j.jinf.2024.106312
Oskar Ljungquist , Michal Magda , Christian G. Giske , Chaitanya Tellapragada , Oleksandr Nazarchuk , Dmytro Dmytriiev , Oskar Thofte , Valdemar Öhnström , Erika Matuschek , Anna M. Blom , Kristian Riesbeck

Objectives

Carbapenem- and colistin-resistant Klebsiella pneumoniae were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant K. pneumoniae are pathogenic and capable of causing disease in a broader context.

Methods

Klebsiella pneumoniae clinical isolates (n = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.

Results

Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in pmrB and phoP genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant K. pneumoniae were more serum-resistant, more virulent against G. mellonella larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The iucA, peg-344, rmpA, rmpC, and rmpD genes were associated with increased virulence in animals.

Conclusions

Pandrug-resistant K. pneumoniae in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.
目的:从在乌克兰医院接受治疗的战争受害者体内分离出抗碳青霉烯类和抗大肠杆菌的肺炎克雷伯氏菌。问题是这些对潘生丁耐药的肺炎克雷伯菌是否具有致病性,是否能在更广泛的范围内致病:方法:对肺炎克雷伯菌临床分离株(n = 37)进行抗生素耐药性检测,并进行全基因组测序(WGS)。此外,还通过血清耐药性和两种不同的动物模型检测了它们的致病性:结果:发现属于序列类型(ST)23、147、307、395 和 512 的分离株携带对碳青霉烯类和头孢菌素的耐药基因。九个分离菌株的 pmrB 和 phoP 基因携带与可乐定耐药性相关的点突变。所有细菌都带有多种毒力基因,耐秋水仙素的分离株各带有 10 种不同的基因。与对秋水仙碱敏感的细菌相比,耐秋水仙碱的肺炎克氏菌对血清的抵抗力更强,对G. mellonella幼虫的毒力更强,在小鼠体内的存活率更高。iucA、peg-344、rmpA、rmpC 和 rmpD 基因与动物毒力增强有关:结论:乌克兰的耐潘生丁肺炎克氏菌具有很强的致病力,并能保持其致病性,因此需要防止其传播。
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引用次数: 0
Synergistic evolution: The dynamic adaptation of SARS-CoV-2 and human protective immunity in the real world 协同进化:SARS-CoV-2 和人类保护性免疫在现实世界中的动态适应。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-10 DOI: 10.1016/j.jinf.2024.106310
Yunhui Li , Xiaohan Zhang , Jingkun Yi , Yuan Chen , Jing Liang , Li Wang , Jiayue Ma , Renlong Zhu , Xiaomei Zhang , Di Hu , Yan Jia , Xiaobo Yu , Yajie Wang

Objectives

SARS-CoV-2 is continually evolving with new variants to evade protective immunity and cause new infections. This study aimed to assess infection-acquired immunity and hybrid immunity against re-infection or severe COVID-19.

Methods

During 2020–2023, we collected 890 serum samples from individuals infected with SARS-CoV-2 variants including wild type, D614G, Alpha, Delta, BA.1, BA.2, BA.2.76, BA.5.2, BF.7, XBB, and EG.5. The levels of serum neutralizing antibodies (NAbs) against 18 diverse SARS-CoV-2 variants were determined using a bead-based high-throughput broad neutralizing-antibody assay.

Results

In the initial wave of the COVID-19 pandemic, >75% of the patients demonstrated robust NAb responses against the ancestral SARS-CoV-2, during a period when vaccines were not yet available. After the emergence of the Omicron variant, the seroprevalence of anti-Omicron NAbs among the patients increased rapidly. By April 2023, when XBB variant was predominant, approximately 80% of the patients demonstrated >50% neutralization against the highly immune-evasive XBB lineages. Three serotypes of SARS-CoV-2, namely non-Omicron, Omicron, and XBB serotypes, were identified, with the strong likelihood of further changes occurring as the virus mutating. Generally, NAbs elicited by a previous serotype could not typically effectively protect against another serotype that emerges later in the evolutionary stages.

Conclusion

Our results firstly demonstrated the synergistic evolution between host immunity and SARS-CoV-2 variants in the real world, which would be helpful to develop future vaccines and public health strategies.
目的:SARS-CoV-2 不断演变出新的变种,以逃避保护性免疫并引起新的感染。本研究旨在评估感染获得的免疫力和针对再感染或严重 COVID-19 的混合免疫力:2020-2023年期间,我们收集了890份感染SARS-CoV-2变体的个体血清样本,包括野生型、D614G、Alpha、Delta、BA.1、BA.2、BA.2.76、BA.5.2、BF.7、XBB和EG.5。使用基于微珠的高通量广谱中和抗体检测法测定了针对 18 种不同 SARS-CoV-2 变体的血清中和抗体(NAbs)水平:结果:在 COVID-19 大流行的最初阶段,超过 75% 的患者对 SARS-CoV-2 的祖先表现出强烈的 NAb 反应,而当时还没有疫苗。欧米克隆变种出现后,患者中抗欧米克隆 NAb 的血清流行率迅速上升。到 2023 年 4 月,当 XBB 变体占主导地位时,约 80% 的患者对具有高度免疫侵袭性的 XBB 株系的中和率大于 50%。目前已确定 SARS-CoV-2 有三种血清型,即非 Omicron、Omicron 和 XBB 血清型,随着病毒的变异,极有可能发生进一步的变化。一般来说,由以前的血清型引起的NAbs通常不能有效保护进化阶段后期出现的另一种血清型:我们的研究结果首次证明了现实世界中宿主免疫力与 SARS-CoV-2 变种之间的协同进化,这将有助于未来疫苗和公共卫生策略的开发。
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引用次数: 0
Epidemiological comparison of emergency department presentations with seasonal influenza or COVID-19 and an outcome of intensive care admission or death: A population-based records linkage study in New South Wales, Australia 季节性流感或 COVID-19 与重症监护入院或死亡结果的急诊科就诊流行病学比较:澳大利亚新南威尔士州的一项基于人口的记录关联研究。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-09 DOI: 10.1016/j.jinf.2024.106307
David J. Muscatello , Nectarios Rose , Kishor Kumar Paul , Sandra Ware , Michael M. Dinh , Mohammed Mohsin , Adam T. Craig , Amalie Dyda , Roberto Forero

Background

COVID-19 and seasonal influenza are endemic causes of morbidity and mortality. This study aimed to compare the epidemiology of severe illness and risk of death among patients following emergency department (ED) presentation with either infection.

Methods

De-identified, population-based, emergency department records in New South Wales, Australia, were probabilistically linked to population-level health outcome databases for the period 1 January 2015 to 28 February 2023. Included were patients allocated an ED diagnosis consistent with an acute respiratory infection. Logistic regression was used to examine the association of infecting virus with risk of a severe outcome (intensive care unit admission or death).

Results

Influenza infection was notified in 2335 and COVID-19 in 5053 patients with a severe outcome. The age distribution was similar for both viruses, except in <15-year-olds, where severe influenza was nearly three times more frequent. Overall, the odds of death among patients with COVID-19 was 1.65 (95% CI 1.43, 1.89) times higher than among those with influenza. This declined to 1.49 (95% CI 1.08, 2.06) times during the COVID-19 Omicron variant period.

Conclusions

The Omicron variant arrived when background population COVID-19 vaccination coverage was >90%. Despite that, death was more frequent for COVID-19 than influenza.
背景:COVID-19和季节性流感是导致发病和死亡的地方性原因。本研究旨在比较在急诊科(ED)就诊的感染者中重症患者的流行病学和死亡风险:方法:将澳大利亚新南威尔士州基于人群的去身份化急诊科记录与人群健康结果数据库进行概率链接,时间跨度为 2015 年 1 月 1 日至 2023 年 2 月 28 日。研究对象包括急诊科诊断为急性呼吸道感染的患者。采用逻辑回归法检测感染病毒与严重后果(入住重症监护室或死亡)风险之间的关联:结果:2335 名患者感染了流感,5053 名出现严重后果的患者感染了 COVID-19。除结论外,两种病毒的年龄分布相似:当人群中 COVID-19 疫苗接种率大于 90% 时,Omicron 变种就会出现。尽管如此,与流感相比,COVID-19的致死率更高。
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引用次数: 0
Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection 在 RSV 感染期间,源自婴儿的人鼻腔器官组织显示出相对增加的易感性、上皮反应和细胞毒性。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-09 DOI: 10.1016/j.jinf.2024.106305
Gina M. Aloisio , Divya Nagaraj , Ashley M. Murray , Emily M. Schultz , Trevor McBride , Letisha Aideyan , Erin G. Nicholson , David Henke , Laura Ferlic-Stark , Anubama Rajan , Amal Kambal , Hannah L. Johnson , Elina Mosa , Fabio Stossi , Sarah E. Blutt , Pedro A. Piedra , Vasanthi Avadhanula

Background

Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.

Methods

We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.

Results

Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines.

Conclusions

Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.
背景:呼吸道合胞病毒(RSV)会导致严重的发病率和死亡率,尤其是在幼儿中。与健康成人相比,儿童感染 RSV 后病情更为严重的原因尚不完全清楚:方法:我们使用来自婴儿和成人的体外人类鼻腔类器官平台,研究在 RSV 复制的初始部位--鼻腔上皮--造成这种疾病差异的潜在机制:结果:婴儿来源的人鼻腔类器官-空气-液体界面(HNO-ALIs)系更容易受到早期RSV复制的影响。此外,与成人相比,婴儿来源的 HNO-ALIs 在统计学上显著引起更大的整体细胞因子反应、更多的粘液分泌和更大的细胞损伤。此外,成人的细胞因子反应与卓越的调节性细胞因子反应有关,这也是细胞损伤少于婴儿的原因:我们的数据凸显了婴儿和成人上呼吸道上皮细胞在细胞水平上对 RSV 感染反应的巨大差异。上皮细胞反应的这些差异可能会导致粘膜纤毛清除功能受损,先天免疫反应失调,从而使婴儿比成人更容易感染更严重的 RSV。
{"title":"Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection","authors":"Gina M. Aloisio ,&nbsp;Divya Nagaraj ,&nbsp;Ashley M. Murray ,&nbsp;Emily M. Schultz ,&nbsp;Trevor McBride ,&nbsp;Letisha Aideyan ,&nbsp;Erin G. Nicholson ,&nbsp;David Henke ,&nbsp;Laura Ferlic-Stark ,&nbsp;Anubama Rajan ,&nbsp;Amal Kambal ,&nbsp;Hannah L. Johnson ,&nbsp;Elina Mosa ,&nbsp;Fabio Stossi ,&nbsp;Sarah E. Blutt ,&nbsp;Pedro A. Piedra ,&nbsp;Vasanthi Avadhanula","doi":"10.1016/j.jinf.2024.106305","DOIUrl":"10.1016/j.jinf.2024.106305","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.</div></div><div><h3>Methods</h3><div>We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.</div></div><div><h3>Results</h3><div>Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines.</div></div><div><h3>Conclusions</h3><div>Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106305"},"PeriodicalIF":14.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401811","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}
引用次数: 0
Highly Pathogenic Avian Influenza A(H5N1) virus infection in dairy cattle: Threat of bird flu has expanded to open-air farmed livestock 奶牛感染高致病性甲型禽流感(H5N1)病毒:禽流感的威胁已扩大到露天饲养的牲畜。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-08 DOI: 10.1016/j.jinf.2024.106311
Yitao Li , Zhihua Sun , Xuefeng Liu , Shuo Wei, Yan Zhang, Yining Fuxiang, Jun Qiao, Hui Zhang, Chencheng Xiao
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引用次数: 0
期刊
Journal of Infection
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