Bavarian Health and Food Safety Authority, Oberschleissheim, Germany; Institute of Social Medicine and Health Systems Research, Otto-von-Guericke-University, Magdeburg, Germany.
Robert Koch Institute, Berlin, Germany.
Lancet Infect Dis. 2020 Aug;20(8):920-928. doi: 10.1016/S1473-3099(20)30314-5. Epub 2020 May 15.
In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates.
A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs.
Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3-4·3) and the median serial interval was 4·0 days (3·0-5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0-99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2-32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6-8·9; 11 of 217) among non-household, high-risk contacts.
Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve.
All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.
2019 年 12 月,在中国武汉新发现的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引发了 COVID-19,这是一种表现出发热、咳嗽且常伴有肺炎的呼吸道疾病。世界卫生组织制定了在全球范围内阻断 SARS-CoV-2 传播的战略目标。2020 年 1 月底,德国巴伐利亚州暴发的疫情为研究传播事件、潜伏期和二次感染率提供了机会。
病例定义为经 RT-PCR 确认的 SARS-CoV-2 感染病例。通过病例访谈描述发病时间和症状性质,并确定和分类接触者为高风险(与确诊病例累计面对面接触≥15 分钟,直接接触确诊 COVID-19 患者的分泌物或体液,或作为卫生保健工作者,在没有个人防护设备的情况下与确诊 COVID-19 患者在 2 米内工作)或低风险(所有其他接触者)。高风险接触者被要求在家中隔离 14 天,并对其进行主动跟踪和监测症状,低风险接触者在出现症状时自行报告并接受检测。我们将发热和咳嗽定义为特定症状,并将非特异性症状出现至少 1 天之前定义为前驱期。全基因组测序用于确认流行病学联系,并澄清接触史不明确的传播事件;与流行病学数据相结合,能够精确重建暴露事件和潜伏期。二次感染率通过以下公式计算:病例数除以接触者数,95%置信区间采用 Fisher 确切检验。
0 号病人是一位中国居民,因工作原因访问德国。在四代传播中出现了 16 例后续病例,通常症状较轻且不具特异性。病毒基因组中的特征性突变出现在第二代的基础上,以及第四代的一个病例中。中位潜伏期为 4.0 天(IQR 2.3-4.3),中位序列间隔为 4.0 天(3.0-5.0)。传播事件可能在一个病例(可能还有另外五例)出现症状前就已发生,在四个病例(可能还有另外五例)出现症状当天发生,其余病例在出现症状后或未知时间发生。有一或两个病例是在接触者出现前驱期症状时发生的。在共同隔离的家庭集群中,家庭成员的二次感染率为 75.0%(95%CI 19.0-99.0;四人中的三人),仅一起隔离的家庭接触者为 10.0%(1.2-32.0;两人中的两人),非家庭、高风险接触者为 5.1%(2.6-8.9;217 人中有 11 人)。
尽管我们研究中的患者主要表现出轻微、非特异性症状,但在出现症状之前或当天就具有很强的传染性。此外,潜伏期往往非常短,并且会出现假阴性检测结果。这些结果表明,尽管疫情得到了控制,但成功实现 COVID-19 的长期和全球控制可能很困难。
所有作者均受雇于政府、联邦州或其他公共资助机构,所有费用均由政府、联邦州或其他公共资助机构承担。