Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series
Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series
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DOI：
10.1016/s1473-3099(20)30314-5
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发表时间：
2020-08-01
影响因子：
56.3
通讯作者：
Zapf, Andreas
中科院分区：
文献类型：
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作者：
Boehmer, Merle M.;Buchholz, Udo;Zapf, Andreas
2019年12月，新发现的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）在中国武汉出现，导致COVID-19，这是一种以发烧、咳嗽和经常肺炎为特征的呼吸道疾病。世卫组织制定了阻断SARS-CoV-2在全球传播的战略目标。从2020年1月底开始，德国巴伐利亚州爆发了一场疫情，为研究传播事件、潜伏期和二次发病率提供了机会。方法将1例病例定义为经RT-PCR确诊的SARS-CoV-2感染病例。进行了病例访谈，以描述发病时间和症状性质，并确定接触者并将其分类为高风险（与确诊病例累计面对面接触b> = 15分钟，直接接触确诊COVID-19患者的分泌物或体液，或者卫生保健工作者在没有个人防护装备的情况下在确诊COVID-19患者2米范围内工作）或低风险（所有其他接触者）。高危接触者居家隔离14天，积极随访监测症状，低危接触者自我报告症状后进行检测。我们将发热和咳嗽定义为特异性症状，将前驱期定义为在特异性症状出现前至少1天出现非特异性症状。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；结合流行病学数据，可以精确地重建暴露事件和潜伏期。二次发作率计算为病例数除以接触者数，使用Fisher对95% ci的精确检验。0号患者为中国居民，因工作原因访问德国。随后出现了16例病例，通常具有轻微和非特异性症状，在4代传播中出现。病毒基因组的特征突变发生在第2代的基础上，也发生在第4代的一个病例中。中位潜伏期为4.0 d (IQR 2.3 ~ 4.3)，中位病程间隔为4.0 d（3.0 ~ 5.0）。1例（可能还有5例）的传播事件可能发生在症状前，4例（可能还有5例）的传播事件可能发生在症状出现之日，其余病例可能发生在症状出现之日之后或未知。有一两个病例是由于在前驱期与另一个病例接触所致。在普通隔离的家庭聚集性接触者中，继发发病率为75.0% （95% CI 19.0-99.0； 4人中有3人），在患者隔离前仅一起接触的家庭接触者中，继发发病率为10.0%（1.2-32.0；20人中有2人），在非家庭高危接触者中，继发发病率为5.1%（2.6-8.9；217人中有11人）。虽然我们研究中的患者主要表现为轻微的非特异性症状，但在症状出现之前或当天的传染性很强。此外，潜伏期往往很短，并出现假阴性试验。这些结果表明，尽管疫情得到了控制，但可能难以实现对COVID-19的成功长期和全球遏制。
Background 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.Methods 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.Findings 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.Interpretation 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.