SARS-CoV-2 血清流行率和高危密切接触者的传播风险因素:一项回顾性队列研究。
SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study.
机构信息
National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
National Centre for Infectious Diseases, Singapore; Woodlands Health Campus, National Healthcare Group, Singapore; Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.
出版信息
Lancet Infect Dis. 2021 Mar;21(3):333-343. doi: 10.1016/S1473-3099(20)30833-1. Epub 2020 Nov 2.
BACKGROUND
The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19.
METHODS
This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors.
FINDINGS
Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9-7·1) for 1779 household contacts, 1·3% (0·9-1·9) for 2231 work contacts, and 1·3% (1·0-1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55-69) of COVID-19 diagnoses, and 36% (27-45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82-15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86-16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07-7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21-5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55-6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission.
INTERPRETATION
Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted.
FUNDING
Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.
背景
无症状携带者的比例以及严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)在家庭和非家庭接触者中的传播风险因素仍不清楚。在新加坡,卫生部对每一例确诊的 COVID-19 病例进行广泛的接触追踪,以及对密切接触者实施法律强制隔离和强化健康监测,这为确定社区内 COVID-19 患者的密切接触者的无症状发病率和 SARS-CoV-2 传播风险因素提供了难得的机会。
方法
本回顾性队列研究涉及 2020 年 1 月 23 日至 4 月 3 日期间新加坡所有确诊 COVID-19 病例的密切接触者。家庭接触者定义为与指数 COVID-19 病例同住的人。非家庭密切接触者定义为与指数病例接触至少 30 分钟且距离指数病例 2 米以内的人。新加坡所有 COVID-19 患者均接受住院治疗,仅限医护人员进入。所有密切接触者均接受为期 14 天的隔离,并通过电话每日三次进行症状监测。有症状的接触者接受 SARS-CoV-2 的 PCR 检测。通过密切接触者的 SARS-CoV-2 阳性率来推断二级临床发病率。同意的接触者接受血清学检测和详细的暴露风险评估。贝叶斯模型用于估计漏诊和无症状 SARS-CoV-2 阳性病例的发生率。使用单变量和多变量逻辑回归模型确定 SARS-CoV-2 传播的风险因素。
结果
2020 年 1 月 23 日至 4 月 3 日期间,共确定了与 1114 例经 PCR 确诊的指数病例相关的 7770 名密切接触者(1863 名家庭接触者、2319 名工作接触者和 3588 名社会接触者)。基于症状的 PCR 检测发现 188 例 COVID-19 病例,7582 名密切接触者在隔离期间 SARS-CoV-2 PCR 检测结果均为阴性。在 7518 名(96.8%)有完整数据的密切接触者中,1779 名家庭接触者的二级临床发病率为 5.9%(95%CI 4.9-7.1),2231 名工作接触者为 1.3%(0.9-1.9),3508 名社会接触者为 1.3%(1.0-1.7)。对 1150 名密切接触者(524 名家庭接触者、207 名工作接触者和 419 名社会接触者)的血清学和症状数据进行贝叶斯分析估计,基于症状的 PCR 检测策略漏诊了 62%(95%可信区间 55-69)的 COVID-19 诊断,以及 36%(27-45)的 SARS-CoV-2 感染者无症状。与指数病例同睡一室(多变量比值比[OR]5.38[95%CI 1.82-15.84];p=0.0023)和与指数病例交谈 30 分钟或更长时间(7.86[3.86-16.02];p<0.0001)与家庭接触者中的 SARS-CoV-2 传播有关。在非家庭接触者中,接触超过一个病例(多变量 OR 3.92[95%CI 2.07-7.40],p<0.0001)、与指数病例交谈 30 分钟或更长时间(2.67[1.21-5.88];p=0.015)和与指数病例共用车辆(3.07[1.55-6.08];p=0.0013)与 SARS-CoV-2 传播有关。在家庭和非家庭接触者中,间接接触、共同进餐和共同使用厕所均与 SARS-CoV-2 传播无关。
解释
社区层面的针对性措施应包括保持身体距离和尽量减少言语交流。应检测所有家庭接触者,包括无症状个体。
资金
新加坡卫生部、新加坡国家研究基金会和中国国家自然科学基金。