Clinical Research Department, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Hospital for Tropical Diseases, University College London Hospital, London, UK.
Barcelona Institute for Global Health, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Lancet Infect Dis. 2021 May;21(5):629-636. doi: 10.1016/S1473-3099(20)30985-3. Epub 2021 Feb 2.
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 × 10 copies per mL to 24% when the index case had a viral load of 1 × 10 copies per mL or higher (adjusted odds ratio per log 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 × 10 copies per mL to greater than 66% for those with an initial viral load of 1 × 10 copies per mL or higher (hazard ratio per log 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 × 10 copies per mL to 6 days (4-8) for those with an initial viral load between 1 × 10 and 1 × 10 copies per mL, and 5 days (3-8) for those with an initial viral load higher than 1 × 10 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.
关于哪些变量会影响严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的传播风险、出现有症状 COVID-19 的风险，尤其是与病毒载量的关系，目前数据有限。我们旨在分析与 COVID-19 确诊病例及其接触者相关联的数据，以探讨与 SARS-CoV-2 传播相关的因素。
在这项队列研究中，患者是在 2020 年 3 月 17 日至 4 月 28 日期间进行的一项随机对照试验的一部分被招募，该试验旨在评估羟氯喹是否能降低 SARS-CoV-2 的传播。通过加泰罗尼亚流行病监测应急服务的电子登记册确定 COVID-19 患者及其接触者。我们分析的 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 天内没有报告其住所或工作场所出现 SARS-CoV-2 感染的症状。纳入的接触者为最近有接触史且在入组前 7 天内无 COVID-19 样症状的成年人。通过对鼻咽拭子进行定量 PCR 测量接触者的病毒载量，并在入组时、第 14 天以及参与者报告出现 COVID-19 样症状时进行评估。我们使用回归分析评估传播风险和出现有症状疾病以及潜伏期动态。我们评估了病毒载量与病例特征（年龄、性别、报告症状出现后的天数，以及是否存在发热、咳嗽、呼吸困难、鼻炎和嗅觉丧失）之间的关系，以及与传播风险之间的关系索引病例和接触者的特征。
我们确定了 314 例 COVID-19 患者，其中 282 例（90%）有至少一个接触者（共 753 个接触者），导致 282 个聚集性病例。282 个聚集性病例中有 90 个（32%）有至少一个传播事件。二级发病率为 17%（753 个接触者中的 125 个），当指数病例的病毒载量低于 1×10 拷贝/mL 时，发病率为 12%，当指数病例的病毒载量为 1×10 拷贝/mL 或更高时，发病率为 24%（病毒载量每增加一个对数，调整后的优势比为 1·3，95%CI 1·1-1·5）。传播风险的增加还与家庭接触（3·0，1·59-5·65）和接触者的年龄（每年：1·02，1·01-1·04）有关。449 名接触者基线时的 PCR 结果为阳性。449 名接触者中有 28 名（6%）在第一次就诊时有症状。在第一次就诊时无症状的 421 名接触者中，181 名（43%）出现有症状 COVID-19，从最初病毒载量低于 1×10 拷贝/mL 的接触者的大约 38%到初始病毒载量为 1×10 拷贝/mL 或更高的接触者的大于 66%（病毒载量每增加一个对数，风险比为 1·12，95%CI 1·05-1·20；p=0·0006）。有症状疾病的发病时间中位数从最初病毒载量低于 1×10 拷贝/mL 的接触者的 7 天（5-10）减少到最初病毒载量为 1×10 到 1×10 拷贝/mL 的接触者的 6 天（4-8），和最初病毒载量高于 1×10 拷贝/mL 的接触者的 5 天（3-8）。
在我们的研究中，指数病例的病毒载量是 SARS-CoV-2 传播的主要驱动因素。接触者的病毒载量与有症状 COVID-19 的风险密切相关，并呈剂量依赖性缩短 COVID-19 的潜伏期。
YoMeCorono，加泰罗尼亚政府。
Zotero 插件