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The Nicaraguan Pediatric Influenza Cohort Study, 2011-2019: influenza incidence, seasonality, and transmission 尼加拉瓜儿童流感队列研究,2011-2019:流感发病率、季节性和传播
Hannah E Maier, G. Kuan, L. Gresh, G. Chowell, K. Bakker, R. López, N. Sanchez, Brenda López, Amy J Schiller, S. Ojeda, E. Harris, A. Balmaseda, A. Gordon
Background. Children account for a large portion of global influenza burden and transmission, and a better understanding of influenza in children is needed to improve prevention and control strategies. Methods. To examine the incidence and transmission of influenza we conducted a prospective community-based study of children aged 0-14 years in Managua, Nicaragua between 2011 and 2019. Participants were provided with medical care through study physicians and symptomatic influenza was confirmed by RT-PCR. Wavelet analyses were used to examine seasonality. Generalized growth models (GGMs) were used to estimate effective reproduction numbers. Results. From 2011-2019, 3,016 children participated, with an average of ~1,800 participants per year and median follow-up time of 5 years per child, and 48.3% of the cohort in 2019 had been enrolled their entire lives. The overall incidence rates per 100 person-years were 14.5 symptomatic influenza cases (95%CI: 13.9-15.1) and 1.0 influenza-associated ALRI case (95%CI: 0.8-1.1). Symptomatic influenza incidence peaked at age 9-11 months. Infants born during peak influenza circulation had lower incidence in the first year of their lives. The mean effective reproduction number was 1.2 (range 1.02-1.49), and we observed significant annual patterns for influenza and influenza A, and a 2.5-year period for influenza B. Conclusions. This study provides important information for understanding influenza epidemiology and informing influenza vaccine policy. These results will aid in informing strategies to reduce the burden of influenza.
背景。儿童占全球流感负担和传播的很大一部分,需要更好地了解儿童流感,以改进预防和控制战略。方法。为了检查流感的发病率和传播,我们在2011年至2019年期间对尼加拉瓜马那瓜0-14岁儿童进行了一项前瞻性社区研究。研究医生为参与者提供医疗护理,并通过RT-PCR证实有症状的流感。小波分析用于检验季节性。使用广义生长模型(GGMs)估计有效繁殖数。结果。从2011年到2019年,共有3016名儿童参与,平均每年约1800名参与者,每个儿童的中位随访时间为5年,2019年队列中48.3%的儿童终身参与。每100人年的总发病率为14.5例有症状的流感病例(95%CI: 13.9-15.1)和1.0例流感相关的ALRI病例(95%CI: 0.8-1.1)。有症状的流感发病率在9-11个月大时达到高峰。在流感流行高峰期出生的婴儿在其生命的第一年发病率较低。平均有效繁殖数为1.2(范围1.02-1.49),我们观察到流感和甲型流感的年周期显著,乙型流感的周期为2.5年。本研究为了解流感流行病学和制定流感疫苗政策提供了重要信息。这些结果将有助于为减轻流感负担的战略提供信息。
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引用次数: 6
A Link Between Obesity and Coronavirus Disease 2019 肥胖与2019冠状病毒病之间的联系
S. Deresinski
Martinez-Colòn GJ, Ratnasari K, Chen H, et al. SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19. bioRxiv 2021.10.24.465626; doi: https:// doi.org/10.1101/2021.10.24.465626. Adipose tissue has previously been shown to serve as a reservoir for influenza A virus as well as human immunodeficiency virus, and obesity is associated with unfavorable outcomes of influenza A virus infection [1]. Obesity is also a strong independent risk factor for coronavirus disease 2019 (COVID-19) infection, as well as for disease severity and associated mortality. Although obesity, especially with associated insulin resistance, is known to be a proinflammatory and hypercoagulable state, the reasons for the detrimental relationship between obesity and COVID-19 have remained undefined. In order to examine the potential role of adipose tissue in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the pathophysiology of the inflammatory response in COVID19, Martinez-Colòn et al secured freshly obtained subcutaneous, visceral, pericardial, and epicardial tissues from individuals undergoing bariatric or cardiac surgery. In addition, they obtained multiple samples from autopsy material of patients who died with COVID-19. Stromal vascular cells (SVCs) were separated from mature adipocytes by collagenase digestion of these tissues. The investigators demonstrated in vitro infection of SVCs and, by flow cytometry, that viral N protein expression was primarily restricted to macrophages. Angiotensin-converting enzyme 2 (ACE-2) expression was, however, very limited in SVCs, with its detection in only approximately 3% of macrophages and with none detected in other tissue types. The macrophages that were infectable were predominantly (85%) type C2, while >11% were C12. Infected C2 macrophages had enrichment of interleukin 10–associated signaling pathways as well as of chemokine and other pathways associated with the innate immune system. At the same time, there was reduced enrichment in host cell translation machinery. Both freshly isolated mature adipocytes and adipocytes differentiated in in vitro culture were susceptible to infection. Genomic RNA and positive sense subgenomic RNA consistent with productive infection were detected. Preadipocytes were not infected but had undergone proinflammatory activation as associates of infected SVCs. In vivo infection of adipose tissue was also demonstrated. SARS-CoV-2 was detected in epicardial, visceral, and subcutaneous adipose tissue as well as in lung, heart, and kidney. The highest concentrations were found in lung, followed by adipose tissue. The investigators have provided evidence that contributes to our understanding of the relationship between obesity and COVID-19 risk. They demonstrated that SARS-CoV-2 primarily infects macrophages in SVCs and that it enters these cells by a means that appears to be independent of host cell ACE-2 expression. This leads
Martinez-Colòn GJ, Ratnasari K,陈海,等。SARS-CoV-2感染人类脂肪组织并引发与严重COVID-19一致的炎症反应。bioRxiv 2021.10.24.465626;Doi: https://doi.org/10.1101/2021.10.24.465626。脂肪组织先前已被证明是甲型流感病毒和人类免疫缺陷病毒的储存库,肥胖与甲型流感病毒感染的不良后果有关[1]。肥胖也是2019冠状病毒病(COVID-19)感染以及疾病严重程度和相关死亡率的一个强大的独立风险因素。虽然肥胖,特别是与胰岛素抵抗相关的肥胖,已知是一种促炎和高凝状态,但肥胖与COVID-19之间有害关系的原因仍不明确。为了研究脂肪组织在严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染中的潜在作用以及covid - 19中炎症反应的病理生理学,Martinez-Colòn等人从接受减肥或心脏手术的患者身上获取了新鲜的皮下、内脏、心包和心外膜组织。此外,他们还从COVID-19死亡患者的尸检材料中获得了多个样本。通过胶原酶消化从成熟脂肪细胞中分离基质血管细胞(SVCs)。研究人员证实体外感染SVCs,并通过流式细胞术证实病毒N蛋白的表达主要局限于巨噬细胞。然而,血管紧张素转换酶2 (ACE-2)在SVCs中的表达非常有限,仅在约3%的巨噬细胞中检测到,在其他组织类型中未检测到。可感染的巨噬细胞以C2型为主(85%),C12型占11%以上。感染的C2巨噬细胞富集白细胞介素10相关信号通路以及趋化因子等与先天免疫系统相关的通路。同时,宿主细胞翻译机制中的富集量减少。新鲜分离的成熟脂肪细胞和体外培养分化的脂肪细胞均易受感染。检测到与生产性感染一致的基因组RNA和阳性亚基因组RNA。前脂肪细胞未被感染,但作为感染的SVCs的附属细胞经历了促炎激活。体内脂肪组织感染也被证实。在心外膜、内脏和皮下脂肪组织以及肺、心脏和肾脏中检测到SARS-CoV-2。肺中浓度最高,其次是脂肪组织。研究人员提供的证据有助于我们理解肥胖与COVID-19风险之间的关系。他们证明,SARS-CoV-2主要感染SVCs中的巨噬细胞,并通过一种似乎独立于宿主细胞ACE-2表达的方式进入这些细胞。这导致受影响的脂肪组织的促炎途径和细胞因子和血管因子的分泌上调。
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引用次数: 0
Omicron Variant Escapes Therapeutic Monoclonal Antibodies (mAbs) Including Recently Released Evusheld®, Contrary to 8 Prior Main Variant of Concern (VOC) Omicron变体逃避治疗性单克隆抗体(mab),包括最近发布的Evusheld®,与之前的8种主要关注变体(VOC)相反
Céline Boschi, P. Colson, Audrey Bancod, V. Moal, B. La Scola
Monocolonal antibodies (mAbs) are currently used for active immunization of COVID-19 in immunocompromised patients. We herein show that in spite there are variations in susceptibility to available mAbs that are authorized for clinical use in France tested on the original B.1.1 virus and 9 variants of concern or of interest, the cocktail casirivimab/imdevimab (REGN-CoV-2) showed a major synergistic effect. However, none of the four mAbs either alone or in combination neutralized the new Omicron variant. Our data strongly warrant a reinforcement of protective measures against infection for immunocompromised patients.
单克隆抗体(mab)目前用于免疫功能低下患者的COVID-19主动免疫。我们在此表明,尽管对法国授权临床使用的现有单克隆抗体的易感性存在差异,但在对原B.1.1病毒和9种关注或感兴趣的变体进行测试时,鸡尾酒casirivimab/imdevimab (REGN-CoV-2)显示出主要的协同效应。然而,这四种单克隆抗体无论是单独的还是组合的都不能中和新的欧米克隆变体。我们的数据强烈要求加强免疫功能低下患者的感染保护措施。
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引用次数: 11
Effectiveness of BNT162b2 and mRNA-1273 Second Doses and Boosters for SARS-CoV-2 infection and SARS-CoV-2 Related Hospitalizations: A Statewide Report from the Minnesota Electronic Health Record Consortium BNT162b2和mRNA-1273二次剂量和增强剂对SARS-CoV-2感染和SARS-CoV-2相关住院治疗的有效性:明尼苏达州电子健康记录联盟的全州报告
P. Drawz, M. DeSilva, Peter J. Bodurtha, Gabriela Vazquez Benitez, A. Murray, A. Chamberlain, R. Dudley, S. Waring, A. Kharbanda, Daniel P Murphy, Miriam H. Muscoplat, V. Meléndez, K. Margolis, Lynn McFarling, Roxana A. Lupu, T. Winkelman, Steven M. Johnson
Using vaccine data combined with electronic health records, we report that mRNA boosters provide greater protection than a two-dose regimen against SARS-CoV-2 infection and related hospitalizations. The benefit of a booster was more evident in the elderly and those with comorbidities. These results support the case for COVID-19 boosters.
利用疫苗数据与电子健康记录相结合,我们报告mRNA增强剂比双剂量方案对SARS-CoV-2感染和相关住院治疗提供更大的保护。在老年人和有合并症的患者中,增强剂的益处更为明显。这些结果支持了COVID-19助推器的情况。
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引用次数: 9
COVID-19 Severity among Women of Reproductive Age with Symptomatic Laboratory-Confirmed SARS-CoV-2 by Pregnancy Status – United States, Jan 1, 2020 – Dec 25, 2021 美国,2020年1月1日至2021年12月25日,按妊娠状况对有症状的实验室确诊的SARS-CoV-2育龄妇女的COVID-19严重程度
P. Strid, L. Zapata, Van T. Tong, Laura D. Zambrano, K. Woodworth, Aspen P. Riser, R. Galang, S. Gilboa, S. Ellington
Abstract Background Information on the severity of COVID-19 attributable to the Delta variant in the United States among pregnant people is limited. We assessed the risk for severe COVID-19 by pregnancy status in the period of Delta variant predominance compared with the pre-Delta period. Methods Laboratory-confirmed SARS-CoV-2 infections among symptomatic women of reproductive age (WRA) were assessed. We calculated adjusted risk ratios for severe disease including intensive care unit (ICU) admission, receipt of invasive ventilation or extracorporeal membrane oxygenation (ECMO), and death comparing the pre-Delta period (January 1, 2020 – June 26, 2021) and the Delta period (June 27, 2021 – December 25, 2021) for pregnant and nonpregnant WRA. Results Compared with the pre-Delta period, the risk of ICU admission during the Delta period was 41% higher (adjusted risk ratio [aRR] 1.41; 95% CI, 1.17-1.69) for pregnant WRA and 9% higher (aRR 1.09; 95% CI, 1.00-1.18) for nonpregnant WRA. The risk of invasive ventilation or ECMO was higher for pregnant (aRR 1.83; 95% CI, 1.26-2.65) and nonpregnant WRA (aRR 1.34; 95% CI, 1.17-1.54) in the Delta period. During the Delta period, the risk of death was 3.33 (95% CI, 2.48-4.46) times the risk in the pre-Delta period among pregnant WRA and 1.62 (95% CI, 1.49-1.77) among nonpregnant WRA. Conclusions Compared with the pre-Delta period, pregnant and nonpregnant WRA were at increased risk for severe COVID-19 in the Delta period.
背景在美国孕妇中Delta变异导致的COVID-19严重程度的信息有限。我们评估了Delta型变异优势期和前Delta期妊娠状况对重症COVID-19的风险。方法对有症状的育龄妇女(WRA)实验室确诊的SARS-CoV-2感染情况进行评估。我们计算了严重疾病的调整风险比,包括重症监护病房(ICU)入住、接受有创通气或体外膜氧合(ECMO)和死亡,并比较了妊娠期和非妊娠期WRA的Delta期(2020年1月1日- 2021年6月26日)和Delta期(2021年6月27日- 2021年12月25日)。结果与Delta期前相比,Delta期住院风险增高41%(调整风险比[aRR] 1.41;妊娠期WRA的95% CI为1.17-1.69),比妊娠期WRA高9% (aRR 1.09;95% CI, 1.00-1.18)。孕妇有创通气或ECMO的风险更高(aRR 1.83;95% CI, 1.26-2.65)和非妊娠期WRA (aRR 1.34;95% CI, 1.17-1.54)。在Delta期,怀孕WRA的死亡风险是Delta期前的3.33倍(95% CI, 2.48-4.46),非怀孕WRA的死亡风险是1.62倍(95% CI, 1.49-1.77)。结论与三角洲期前相比,妊娠期和非妊娠期WRA发生重症COVID-19的风险增加。
{"title":"COVID-19 Severity among Women of Reproductive Age with Symptomatic Laboratory-Confirmed SARS-CoV-2 by Pregnancy Status – United States, Jan 1, 2020 – Dec 25, 2021","authors":"P. Strid, L. Zapata, Van T. Tong, Laura D. Zambrano, K. Woodworth, Aspen P. Riser, R. Galang, S. Gilboa, S. Ellington","doi":"10.21203/rs.3.rs-1090075/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-1090075/v1","url":null,"abstract":"Abstract Background Information on the severity of COVID-19 attributable to the Delta variant in the United States among pregnant people is limited. We assessed the risk for severe COVID-19 by pregnancy status in the period of Delta variant predominance compared with the pre-Delta period. Methods Laboratory-confirmed SARS-CoV-2 infections among symptomatic women of reproductive age (WRA) were assessed. We calculated adjusted risk ratios for severe disease including intensive care unit (ICU) admission, receipt of invasive ventilation or extracorporeal membrane oxygenation (ECMO), and death comparing the pre-Delta period (January 1, 2020 – June 26, 2021) and the Delta period (June 27, 2021 – December 25, 2021) for pregnant and nonpregnant WRA. Results Compared with the pre-Delta period, the risk of ICU admission during the Delta period was 41% higher (adjusted risk ratio [aRR] 1.41; 95% CI, 1.17-1.69) for pregnant WRA and 9% higher (aRR 1.09; 95% CI, 1.00-1.18) for nonpregnant WRA. The risk of invasive ventilation or ECMO was higher for pregnant (aRR 1.83; 95% CI, 1.26-2.65) and nonpregnant WRA (aRR 1.34; 95% CI, 1.17-1.54) in the Delta period. During the Delta period, the risk of death was 3.33 (95% CI, 2.48-4.46) times the risk in the pre-Delta period among pregnant WRA and 1.62 (95% CI, 1.49-1.77) among nonpregnant WRA. Conclusions Compared with the pre-Delta period, pregnant and nonpregnant WRA were at increased risk for severe COVID-19 in the Delta period.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73353480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Correlates of COVID-19 Vaccine Hesitancy among People who Inject Drugs in the San Diego-Tijuana Border Region 圣地亚哥-蒂华纳边境地区注射吸毒者中COVID-19疫苗犹豫的相关因素
S. Strathdee, D. Abramovitz, Alicia Y Harvey-Vera, Carlos F. Vera, G. Rangel, Irina Artamonova, T. Patterson, Rylie A Mitchell, A. Bazzi
Background: People who inject drugs (PWID) are vulnerable to acquiring SARS-CoV-2 but their barriers to COVID-19 vaccination are under-studied. We examined correlates of COVID-19 vaccine hesitancy among PWID in the U.S.-Mexico border region, of whom only 7.6% had received [≥]one COVID-19 vaccine dose by September, 2021. Methods: Between October, 2020 and September, 2021, participants aged [≥]18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month completed surveys and SARS-CoV-2, HIV, and HCV serologic testing. Logistic regressions with robust standard error estimation via generalized estimating equations identified factors associated with COVID-19 vaccine hesitancy, defined as being unsure or unwilling to receive COVID-19 vaccines. Results: Of 393 participants, 127 (32.3%) were vaccine hesitant. Older participants, those with greater food insecurity, and those with greater concern about acquiring SARS-CoV-2 were more willing to be vaccinated. Higher numbers of chronic health conditions, having access to a smart phone or computer, and citing social media as one's most important source of COVID-19 information were independently associated with vaccine hesitancy. COVID-19-related disinformation was independently associated with vaccine hesitancy (adjusted odds ratio: 1.51 per additional conspiracy theory endorsed; 95% confidence interval: 1.31-1.74). Conclusions: Nearly one third of PWID in the San Diego-Tijuana border region reported COVID-19 vaccine hesitancy, which was significantly influenced by exposure to disinformation. Interventions that improve accurate knowledge and trust in COVID-19 vaccines are needed to increase vaccination in this vulnerable population.
背景:注射吸毒者(PWID)容易感染SARS-CoV-2,但他们接种COVID-19疫苗的障碍尚未得到充分研究。我们检查了美墨边境地区PWID中COVID-19疫苗犹豫的相关因素,其中只有7.6%的人在2021年9月之前接种了[≥]一剂COVID-19疫苗。方法:在2020年10月至2021年9月期间,来自美国加利福尼亚州圣地亚哥和墨西哥下加利福尼亚州蒂华纳的年龄[≥]18岁的注射吸毒者完成了调查和SARS-CoV-2、HIV和HCV血清学检测。通过广义估计方程进行鲁棒标准误差估计的Logistic回归确定了与COVID-19疫苗犹豫相关的因素,犹豫被定义为不确定或不愿接种COVID-19疫苗。结果:在393名参与者中,127名(32.3%)对疫苗犹豫。年龄较大的参与者、粮食不安全程度较高的参与者以及更担心感染SARS-CoV-2的参与者更愿意接种疫苗。患有慢性疾病、使用智能手机或电脑以及将社交媒体作为COVID-19信息的最重要来源的人数较多,与疫苗犹豫独立相关。与covid -19相关的虚假信息与疫苗犹豫独立相关(调整后的优势比:每增加一个支持的阴谋论1.51;95%置信区间:1.31-1.74)。结论:圣地亚哥-蒂华纳边境地区近三分之一的PWID报告了COVID-19疫苗犹豫,这受到虚假信息暴露的显着影响。需要采取干预措施,提高对COVID-19疫苗的准确认识和信任,以增加这一弱势人群的疫苗接种。
{"title":"Correlates of COVID-19 Vaccine Hesitancy among People who Inject Drugs in the San Diego-Tijuana Border Region","authors":"S. Strathdee, D. Abramovitz, Alicia Y Harvey-Vera, Carlos F. Vera, G. Rangel, Irina Artamonova, T. Patterson, Rylie A Mitchell, A. Bazzi","doi":"10.1101/2021.10.29.21265669","DOIUrl":"https://doi.org/10.1101/2021.10.29.21265669","url":null,"abstract":"Background: People who inject drugs (PWID) are vulnerable to acquiring SARS-CoV-2 but their barriers to COVID-19 vaccination are under-studied. We examined correlates of COVID-19 vaccine hesitancy among PWID in the U.S.-Mexico border region, of whom only 7.6% had received [≥]one COVID-19 vaccine dose by September, 2021. Methods: Between October, 2020 and September, 2021, participants aged [≥]18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month completed surveys and SARS-CoV-2, HIV, and HCV serologic testing. Logistic regressions with robust standard error estimation via generalized estimating equations identified factors associated with COVID-19 vaccine hesitancy, defined as being unsure or unwilling to receive COVID-19 vaccines. Results: Of 393 participants, 127 (32.3%) were vaccine hesitant. Older participants, those with greater food insecurity, and those with greater concern about acquiring SARS-CoV-2 were more willing to be vaccinated. Higher numbers of chronic health conditions, having access to a smart phone or computer, and citing social media as one's most important source of COVID-19 information were independently associated with vaccine hesitancy. COVID-19-related disinformation was independently associated with vaccine hesitancy (adjusted odds ratio: 1.51 per additional conspiracy theory endorsed; 95% confidence interval: 1.31-1.74). Conclusions: Nearly one third of PWID in the San Diego-Tijuana border region reported COVID-19 vaccine hesitancy, which was significantly influenced by exposure to disinformation. Interventions that improve accurate knowledge and trust in COVID-19 vaccines are needed to increase vaccination in this vulnerable population.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90069614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
Age-Specific Changes in Virulence Associated with SARS-CoV-2 Variants of Concern 与SARS-CoV-2变体相关的毒力的年龄特异性变化
D. Fisman, A. Tuite
Background: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of SARS-CoV-2. The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs is similar across the age spectrum, or is limited to some age groups, is unknown. Methods: We created a retrospective cohort of people in Ontario, Canada testing positive for SARS-CoV-2 and screened for VOCs, with dates of test report between February 7 and August 30, 2021 (n=233,799). Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate the effects of N501Y-postive or Delta VOC infections on infection severity, using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, time, health unit, vaccination status, comorbidities, immune compromise, long-term care residence, healthcare worker status, and pregnancy. Results: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death in younger and older adults, compared to infections where a VOC was not detected. Delta VOC increased hospitalization risk in children under 10 by a factor of 2.5 (adjusted odds ratio, 95% confidence interval: 1.2 to 5.1) compared to non-VOC. For most VOC-outcome combinations there was no heterogeneity in adverse outcomes by age. However, there was an inverse relationship between age and relative increase in risk of death with delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals. Interpretation: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.
背景:新型关注变异体(VOCs)与SARS-CoV-2的传染性和毒力增加有关。SARS-CoV-2的毒力与年龄密切相关。新型挥发性有机化合物毒性的相对增加是否在整个年龄范围内相似,还是仅限于某些年龄组,目前尚不清楚。方法:我们在加拿大安大略省建立了一个回顾性队列,对SARS-CoV-2检测呈阳性并进行了voc筛查,检测报告日期为2021年2月7日至8月30日(n= 233799)。病例分为n501y阳性VOC,可能的Delta VOC或未检测到VOC。我们构建了特定年龄的逻辑回归模型,以住院、重症监护病房(ICU)入院和死亡为结果变量,评估n501y阳性或Delta VOC感染对感染严重程度的影响。模型根据性别、时间、卫生单位、疫苗接种状况、合并症、免疫损害、长期护理住所、卫生保健工作者状况和怀孕进行了调整。结果:与未检测到挥发性有机化合物的感染相比,n501y阳性或δ型挥发性有机化合物感染与年轻人和老年人住院、ICU住院和死亡风险的显著升高相关。与非挥发性有机化合物相比,10岁以下儿童的住院风险增加了2.5倍(校正优势比,95%置信区间:1.2至5.1)。对于大多数voc结局组合,不良结局在年龄方面没有异质性。然而,年龄与δ VOC死亡风险的相对增加之间存在反比关系,年轻年龄组的死亡风险相对增加高于老年人。解释:在所有年龄组中,SARS-CoV-2挥发性有机化合物似乎与感染的相对毒性增加有关,尽管年轻个体的绝对结果数量较低,使得这些年龄组的估计不准确。
{"title":"Age-Specific Changes in Virulence Associated with SARS-CoV-2 Variants of Concern","authors":"D. Fisman, A. Tuite","doi":"10.1101/2021.09.25.21264097","DOIUrl":"https://doi.org/10.1101/2021.09.25.21264097","url":null,"abstract":"Background: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of SARS-CoV-2. The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs is similar across the age spectrum, or is limited to some age groups, is unknown. Methods: We created a retrospective cohort of people in Ontario, Canada testing positive for SARS-CoV-2 and screened for VOCs, with dates of test report between February 7 and August 30, 2021 (n=233,799). Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate the effects of N501Y-postive or Delta VOC infections on infection severity, using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, time, health unit, vaccination status, comorbidities, immune compromise, long-term care residence, healthcare worker status, and pregnancy. Results: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death in younger and older adults, compared to infections where a VOC was not detected. Delta VOC increased hospitalization risk in children under 10 by a factor of 2.5 (adjusted odds ratio, 95% confidence interval: 1.2 to 5.1) compared to non-VOC. For most VOC-outcome combinations there was no heterogeneity in adverse outcomes by age. However, there was an inverse relationship between age and relative increase in risk of death with delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals. Interpretation: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77606198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Long Term Accuracy of SARS-CoV-2 Interferon-γ Release Assay and its Application in Household Investigation SARS-CoV-2干扰素γ释放法的长期准确性及其在入户调查中的应用
K. Murugesan, P. Jagannathan, J. Altamirano, Y. Maldonado, H. Bonilla, K. Jacobson, J. Parsonnet, J. Andrews, R. Shi, S. Boyd, B. Pinsky, U. Singh, N. Banaei
Background: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. Methods: The performance of a whole blood interferon-gamma (IFN-{gamma}) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific CD4 and CD8 T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. Results: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-{gamma} response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. Conclusions: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.
背景:流行病学调查和T细胞介导的疫苗免疫应答的临床评估需要一种能够敏感检测细胞介导的SARS-CoV-2免疫应答的免疫诊断试验,特别是在可能逃避抗体应答的新变体的背景下。方法:采用全血干扰素- γ (IFN-{γ})释放试验(IGRA)检测SARS-CoV-2抗原特异性CD4和CD8 T细胞,对感染后连续检测10个月的COVID-19恢复期患者和健康献血者进行评价。对有指示病例的家庭接触者应用SARS-CoV-2 IGRA。肝素锂管中新鲜采集的血液不受刺激,用SARS-CoV-2肽池刺激,并用有丝分裂原刺激。结果:IGRA的总体敏感性和特异性为84.5% (153/181;95%置信区间[CI] 79.0-89.0)和86.6% (123/142;95% CI;80.0-91.2)。灵敏度从100% (16/16;感染后0.5个月95% CI为80.6-100)至79.5% (31/39;感染后10个月95% CI 64.4 ~ 89.2) (P<0.01)。在感染后10个月,IFN-{γ}反应仍然相对强劲(分别为3.8和1.3 IU/mL)。14户家庭IGRA阳性率分别为100%(12/12)和65.2% (15/23),IgG阳性率分别为50.0%(6/12)和43.5%(10/23),差异分别为+50% (95% CI +25.4 ~ +74.6)和+21.7% (95% CI +9.23 ~ +42.3)。100%(12/12)的指示病例和73.9%(17/23)的接触者IGRA或IgG阳性。结论:SARS-CoV-2 IGRA是评估细胞介导的SARS-CoV-2免疫应答的有效临床诊断工具。
{"title":"Long Term Accuracy of SARS-CoV-2 Interferon-γ Release Assay and its Application in Household Investigation","authors":"K. Murugesan, P. Jagannathan, J. Altamirano, Y. Maldonado, H. Bonilla, K. Jacobson, J. Parsonnet, J. Andrews, R. Shi, S. Boyd, B. Pinsky, U. Singh, N. Banaei","doi":"10.1101/2021.09.20.21263527","DOIUrl":"https://doi.org/10.1101/2021.09.20.21263527","url":null,"abstract":"Background: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. Methods: The performance of a whole blood interferon-gamma (IFN-{gamma}) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific CD4 and CD8 T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. Results: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-{gamma} response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. Conclusions: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84778364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Measuring Vaccine Efficacy Against Infection and Disease in Clinical Trials: Sources and Magnitude of Bias in Coronavirus Disease 2019 (COVID-19) Vaccine Efficacy Estimates 在临床试验中测量疫苗对感染和疾病的有效性:2019年冠状病毒病(COVID-19)疫苗有效性估计的偏倚来源和程度
L. Williams, N. Ferguson, C. Donnelly, N. Grassly
Background Phase III trials have estimated COVID-19 vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections. Methods We developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic and any SARS-CoV-2 infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections. Results VE against asymptomatic infection measured by PCR or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias towards underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4 to 77.1) and 70.9% (95% UI 49.8 to 80.7) respectively. Conclusion Multiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.
III期试验估计了COVID-19疫苗对有症状和无症状感染的有效性。我们探讨了这些估计中潜在偏差的方向和程度,以及它们对疫苗保护免受感染和突破性感染疾病的影响。方法建立了一个数学模型,该模型考虑了自然免疫和疫苗诱导免疫、血清状态变化以及感染和抗体检测的不完美敏感性和特异性。我们根据一系列疫苗特征和测量方法估计了VE对有症状、无症状和任何SARS-CoV-2感染以及感染后疾病的预期偏倚,以及对包括无症状感染的已发表试验结果的可能总体偏倚。结果对于预防疾病而非感染的疫苗,PCR或血清学检测对无症状感染的VE可能较低或阴性。当无症状感染比有症状感染更不可能被发现,并且疫苗可以防止症状发展时,对任何感染的VE都被高估了。对于基于不完全特异性的测试的估计,特别是在频繁进行测试的情况下,会产生低估的竞争性偏见。我们的模型表明,Oxford-AstraZeneca ChAdOx1和Janssen Ad26.COV2具有相当大的不确定性。对任何感染的S - VE,略高于已发表的偏倚校正值59.0%(95%不确定区间[UI] 38.4至77.1)和70.9% (95% UI为49.8至80.7)。结论多重偏倚可能会影响COVID-19 VE的估计,这可能解释了ChAdOx1和Ad26.COV2之间观察到的差异。年代的疫苗。在解释疗效和有效性研究结果时应考虑这些偏差。
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引用次数: 4
Effectiveness of 13-valent pneumococcal conjugate vaccine against medically-attended lower respiratory tract infection and pneumonia among older adults 13价肺炎球菌结合疫苗对老年人下呼吸道感染和肺炎的有效性
J. Lewnard, K. Bruxvoort, Heidi Fischer, V. Hong, L. Grant, L. Jodar, A. Cane, B. Gessner, S. Tartof
Importance: In 2014, the US Advisory Committee on Immunization Practices (ACIP) extended existing pneumococcal vaccination recommendations for adults aged [≥]65 years to include 13-valent pneumococcal conjugate vaccine (PCV13), primarily to prevent non-bacteremic pneumonia. Objective: To determine PCV13 effectiveness against all-cause inpatient plus outpatient medically-attended lower-respiratory tract infection (LRTI) and pneumonia among US older adults. Design: Prospective, open cohort study following participants from 2016 to 2019. We conducted analyses in a self-matched framework, comparing outcomes during participants' follow-up periods before and after receipt of PCV13. Setting: Kaiser Permanente Southern California (KPSC) integrated healthcare delivery system. Participants: Adults aged [≥]65 years who received PCV13 between 2016-2019. Exposures: Receipt of PCV13 at ages [≥]65 years, concordant with ACIP guidelines. Main outcomes and measures: We estimated the adjusted hazards ratio (aHR) for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. We computed aHR estimates using Cox proportional hazards models. We defined vaccine effectiveness (VE) as (1-aHR)*100%. We also estimated PCV13-attributable absolute reductions in incidence of LRTI and pneumonia. Results: Observations were available both before and after PCV13 receipt for 42,700 participants. Among these individuals, 1,419 experienced LRTI and 969 experienced pneumonia over approximately 26,000 combined years of follow-up before PCV13 receipt; 3,849 experienced LRTI and 2,727 experienced pneumonia over approximately 74,000 combined years of follow-up after PCV13 receipt. In adjusted analyses, VE was 9.5% (95% confidence interval: 2.2% to 16.3%) against all-cause medically-attended LRTI and 8.8% (-0.2% to 17.0%) against all-cause medically-attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of 23-valent pneumococcal polysaccharide vaccine. We estimated that PCV13 prevented 0.7 (0.2 to 1.4) and 0.5 (0.0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually. Over a five-year time horizon, one case of LRTI and pneumonia, respectively, was prevented for every 27 (14 to 116) and 42 (-97 to 268) individuals receiving PCV13. Conclusions and relevance: PCV13 vaccination among older adults reduced the burden of medically-attended respiratory illness in this population.
重要性:2014年,美国免疫实践咨询委员会(ACIP)扩大了现有的65岁以上成人肺炎球菌疫苗接种建议,包括13价肺炎球菌结合疫苗(PCV13),主要用于预防非菌源性肺炎。目的:确定PCV13对美国老年人全因住院和门诊医疗护理下呼吸道感染(LRTI)和肺炎的有效性。设计:前瞻性、开放式队列研究,2016 - 2019年随访。我们在一个自我匹配的框架中进行了分析,比较了参与者在接受PCV13之前和之后的随访期间的结果。环境:南加州凯撒医疗机构(KPSC)综合医疗保健服务系统。参与者:2016-2019年期间接受PCV13治疗的65岁[≥]成年人。暴露:年龄[≥]65岁接受PCV13,符合ACIP指南。主要结局和测量:我们估计了每个呼吸季节首次LRTI和肺炎发作的调整危险比(aHR),使用自匹配推断框架比较每个参与者暴露于pcv13和未暴露于pcv13的风险时间。我们使用Cox比例风险模型计算aHR估计。我们将疫苗有效性(VE)定义为(1-aHR)*100%。我们还估计了pcv13可导致下呼吸道感染和肺炎发生率的绝对降低。结果:42,700名参与者在接受PCV13之前和之后都有观察结果。在这些个体中,1419人经历了LRTI, 969人经历了肺炎,在接受PCV13之前的随访时间总计约26,000年;在接受PCV13后约74,000年的随访中,3,849例发生LRTI, 2,727例发生肺炎。在校正分析中,全因医务人员参与的LRTI组VE为9.5%(95%可信区间:2.2%至16.3%),全因医务人员参与的肺炎组VE为8.8%(-0.2%至17.0%)。相反,我们没有发现接种23价肺炎球菌多糖疫苗后对LRTI和肺炎有保护作用的证据。我们估计,每年每100名接种疫苗的人中,PCV13分别预防了0.7(0.2至1.4)和0.5(0.0至1.0)例下呼吸道感染和肺炎。在五年的时间范围内,每27例(14至116例)和42例(-97至268例)接受PCV13的个体分别预防1例下呼吸道感染和肺炎。结论和相关性:老年人接种PCV13疫苗减轻了这一人群接受医疗护理的呼吸道疾病负担。
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引用次数: 21
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Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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