Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study.
Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study.
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DOI：
10.1016/s1473-3099(20)30985-3
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Mitjà O
中科院分区：
文献类型：
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作者：
Marks M;Millat-Martinez P;Ouchi D;Roberts CH;Alemany A;Corbacho-Monné M;Ubals M;Tobias A;Tebé C;Ballana E;Bassat Q;Baro B;Vall-Mayans M;G-Beiras C;Prat N;Ara J;Clotet B;Mitjà O
关于哪些变量影响严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）传播风险、症状性COVID-19的发展，特别是与病毒载量的关系，目前缺乏数据。我们旨在分析COVID-19关联指数病例及其接触者的数据，以探索与SARS-CoV-2传播相关的因素。在这项队列研究中，患者被招募作为2020年3月17日至4月28日进行的随机对照试验的一部分，旨在评估羟氯喹是否减少SARS-CoV-2的传播。通过使用加泰罗尼亚（西班牙）流行病学监测紧急服务的电子注册表确定了COVID-19患者及其接触者。我们的分析中纳入的COVID-19患者年龄在18岁或以上，未住院，基线时有定量PCR结果，在入组前5天内出现轻度症状，并且在入组前14天内在其住宿或工作场所没有报告SARS-CoV-2感染症状。接触者包括有近期暴露史且在入组前7天内没有COVID-19样症状的成年人。在入组时、第14天以及参与者报告COVID-19样症状时，通过鼻咽拭子定量PCR测量接触者的病毒载量。我们使用回归分析评估了传播和发展有症状疾病的风险和潜伏动态。我们评估了病毒载量与病例特征（年龄、性别、报告症状出现的天数，以及有无发热、咳嗽、呼吸困难、鼻炎和嗅觉丧失）之间的关系，以及传播风险与指示病例和接触者特征之间的关联。我们确定了314名COVID-19患者，其中282名（90%）至少有一次接触（共753次接触），导致282个集群。在282个集群中，有90个（32%）至少发生了一次传播事件。二次发作率为17%（753名接触者中的125名），从指示病例病毒载量低于1 × 106拷贝/mL时的12%变化到指示病例病毒载量为1 × 1010拷贝/mL或更高时的24%（病毒载量每log 10增加的校正比值比为1.3，95%CI 1.1 - 1.5）。 传播风险增加还与家庭接触（3.0，1.59 - 5.65）和接触者年龄（每年：1.02，1.01 - 1.04）有关。449名接触者在基线时PCR结果呈阳性。449名接触者中有28人（6%）在首次就诊时出现症状。在421名首次就诊时无症状的接触者中，181人（43%）出现了症状性COVID-19，从初始病毒载量低于1 × 107拷贝/mL的接触者中的约38%到初始病毒载量为1 × 1010拷贝/mL或更高的接触者中的66%（病毒载量每log 10增加的风险比为1.12，95% CI 1.05 - 1.20; p= 0.0006）。 至症状性疾病发作的时间从初始病毒载量低于1 × 107拷贝/mL的个体的中位7天（IQR 5-10）缩短至初始病毒载量在1 × 107和1 × 109拷贝/mL之间的个体的6天（4-8），以及初始病毒载量高于1 × 109拷贝/mL的个体的5天（3-8）。 在我们的研究中，指示病例的病毒载量是SARS-CoV-2传播的主要驱动因素。出现症状性COVID-19的风险与基线时接触者的病毒载量密切相关，并以剂量依赖性方式缩短COVID-19的潜伏时间。YoMeCorono，Generalitat de卡塔卢尼亚.摘要的加泰罗尼亚语翻译见补充材料部分。
Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2. In this cohort study, patients were recruited as part of a randomised controlled trial done between March 17 and April 28, 2020, that aimed to assess if hydroxychloroquine reduced transmission of SARS-CoV-2. Patients with COVID-19 and their contacts were identified by use of the electronic registry of the Epidemiological Surveillance Emergency Service of Catalonia (Spain). Patients with COVID-19 included in our analysis were aged 18 years or older, not hospitalised, had quantitative PCR results available at baseline, had mild symptom onset within 5 days before enrolment, and had no reported symptoms of SARS-CoV-2 infections in their accommodation or workplace within the 14 days before enrolment. Contacts included were adults with a recent history of exposure and absence of COVID-19-like symptoms within the 7 days preceding enrolment. Viral load of contacts, measured by quantitative PCR from a nasopharyngeal swab, was assessed at enrolment, at day 14, and whenever the participant reported COVID-19-like symptoms. We assessed risk of transmission and developing symptomatic disease and incubation dynamics using regression analysis. We assessed the relationship of viral load and characteristics of cases (age, sex, number of days from reported symptom onset, and presence or absence of fever, cough, dyspnoea, rhinitis, and anosmia) and associations between risk of transmission and characteristics of the index case and contacts. We identified 314 patients with COVID-19, with 282 (90%) having at least one contact (753 contacts in total), resulting in 282 clusters. 90 (32%) of 282 clusters had at least one transmission event. The secondary attack rate was 17% (125 of 753 contacts), with a variation from 12% when the index case had a viral load lower than 1 × 106 copies per mL to 24% when the index case had a viral load of 1 × 1010 copies per mL or higher (adjusted odds ratio per log10 increase in viral load 1·3, 95% CI 1·1–1·5). Increased risk of transmission was also associated with household contact (3·0, 1·59–5·65) and age of the contact (per year: 1·02, 1·01–1·04). 449 contacts had a positive PCR result at baseline. 28 (6%) of 449 contacts had symptoms at the first visit. Of 421 contacts who were asymptomatic at the first visit, 181 (43%) developed symptomatic COVID-19, with a variation from approximately 38% in contacts with an initial viral load lower than 1 × 107 copies per mL to greater than 66% for those with an initial viral load of 1 × 1010 copies per mL or higher (hazard ratio per log10 increase in viral load 1·12, 95% CI 1·05–1·20; p=0·0006). Time to onset of symptomatic disease decreased from a median of 7 days (IQR 5–10) for individuals with an initial viral load lower than 1 × 107 copies per mL to 6 days (4–8) for those with an initial viral load between 1 × 107 and 1 × 109 copies per mL, and 5 days (3–8) for those with an initial viral load higher than 1 × 109 copies per mL. In our study, the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner. YoMeCorono, Generalitat de Catalunya. For the Catalan translation of the abstract see Supplementary Materials section.