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利用强化高分辨率采样研究严重急性呼吸综合征冠状病毒 2 的脱落和家庭传播的自然史。

Natural history of shedding and household transmission of severe acute respiratory syndrome coronavirus 2 using intensive high-resolution sampling.

机构信息

Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.

Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, United States of America.

出版信息

PLoS One. 2024 Jul 25;19(7):e0305300. doi: 10.1371/journal.pone.0305300. eCollection 2024.

Abstract

IMPORTANCE

The COVID-19 pandemic has led to 775 million documented cases and over 7 million deaths worldwide as of March 2024 and is an ongoing health crisis. To limit viral spread within households and in the community, public health officials have recommended self-isolation, self-quarantine of exposed household contacts, and mask use. Yet, risk of household transmission (HHT) may be underestimated due to low frequency of sampling, and risk factors for HHT are not well understood.

OBJECTIVES

To estimate the secondary attack rate of SARS-CoV-2 within households and to define the risk factors for new infections in household members who are in close contact with the index case.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, from March 2020-December 2021 we enrolled 60 households with index cases who tested positive for SARS-CoV-2. All household contacts and index cases were tested daily for SARS-CoV-2 via reverse transcription polymerase chain reaction (RT-PCR) using self-collected anterior nares specimens. Households were followed until all study participants in the household tested negative for SARS-CoV-2 for seven consecutive days. We collected sex, age, race/ethnicity, comorbidities, and relationship to index case for secondary contacts, household level characteristics including primary income, household density, and square feet per person on property. We compared the sociodemographic variables between COVID-19 positive and negative household members and between households where secondary transmission did and did not occur.

MAIN OUTCOMES AND MEASURES

Daily anterior nares swabs were tested for SARS-CoV-2 using RT-PCR, in order to assess duration of nasal shedding of SARS-CoV-2, as well as risk of transmission to secondary household contacts.

RESULTS

Of the 163 participants in this study, 84 (51.5%) were women; median age (IQR) was 36.0 (17.0-54.0) years of age; 78 (47.8%) were white and 48 (29.5%) were Hispanic/LatinX. Of the fifty households with household contacts, at least one secondary case occurred in twenty-six households (52.0%) and forty-five household contacts (43.7%) were infected. Secondary attack rate was lowest among children of index cases (6/23, 26.1%). Modified Poisson regression identified that the risk of transmission to household contacts increases significantly with age (Risk ratio for each increase in years of age = 1.01, 95% CI = 1.00-1.02). Mixed effects regression models identified that participants with chronic diseases, such as asthma, diabetes, cancer, or cardiac disease, had higher Cts at baseline when compared to participants without chronic diseases (6.62, 95% CI: 1.46-11.77, p = 0.02) and show a slower rate of increase in Ct over time (-0.43, 95% CI: -0.77 to -0.09, p = 0.02).

CONCLUSIONS AND RELEVANCE

This study suggests that HHT represents a key source of community-based infection of SARS-CoV-2. Allocation of resources for contact investigations and prevention interventions should focus on the individuals at highest risk of infection in households, especially those with higher density homes.

摘要

重要性

截至 2024 年 3 月,COVID-19 大流行已在全球范围内导致 7.75 亿例确诊病例和超过 700 万人死亡,这是一场持续的健康危机。为了限制家庭和社区内病毒的传播,公共卫生官员建议自我隔离、暴露的家庭接触者自我检疫和佩戴口罩。然而,由于采样频率低,家庭传播(HHT)的风险可能被低估,并且 HHT 的风险因素尚未得到很好的理解。

目的

估计家庭内 SARS-CoV-2 的二次攻击率,并确定与指数病例密切接触的家庭成员中新感染的风险因素。

设计、设置和参与者:在这项前瞻性队列研究中,我们于 2020 年 3 月至 2021 年 12 月招募了 60 户有 SARS-CoV-2 阳性指数病例的家庭。所有家庭接触者和指数病例均通过自我采集前鼻拭子,使用逆转录聚合酶链反应(RT-PCR)每日检测 SARS-CoV-2。家庭一直随访到家庭中所有研究参与者连续 7 天 SARS-CoV-2 检测均为阴性。我们收集了二级接触者的性别、年龄、种族/民族、合并症和与指数病例的关系,以及包括主要收入、家庭密度和人均居住面积在内的家庭水平特征。我们比较了 COVID-19 阳性和阴性家庭成员以及二级传播发生和未发生的家庭之间的社会人口学变量。

主要结果和措施

每天使用 RT-PCR 检测前鼻拭子以评估 SARS-CoV-2 的鼻脱落持续时间,以及向二级家庭接触者传播的风险。

结果

在这项研究的 163 名参与者中,84 名(51.5%)为女性;中位数(IQR)年龄为 36.0(17.0-54.0)岁;78 名(47.8%)为白人,48 名(29.5%)为西班牙裔/拉丁裔。在 50 户有家庭接触者的家庭中,有 26 户(52.0%)至少有一个二级病例,45 名家庭接触者(43.7%)感染。指数病例的子女中传播风险最低(23 例中有 6 例,26.1%)。修正泊松回归发现,与年龄每增加一年相比,向家庭接触者传播的风险显著增加(年龄每增加一年的风险比=1.01,95%CI:1.00-1.02)。混合效应回归模型发现,与没有慢性病的参与者相比,患有哮喘、糖尿病、癌症或心脏病等慢性病的参与者基线时的 Cts 更高(6.62,95%CI:1.46-11.77,p=0.02),并且 Ct 随时间的增加率较慢(-0.43,95%CI:-0.77 至-0.09,p=0.02)。

结论和相关性

这项研究表明,HHT 代表了 SARS-CoV-2 社区感染的一个主要来源。接触者调查和预防干预资源的分配应重点关注家庭中感染风险最高的个体,尤其是那些居住密度较高的家庭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7346/11271927/06101b375149/pone.0305300.g001.jpg

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