【中英对照】《新英格兰医学杂志》（NEJM）——新型冠状病毒肺炎在中国武汉的早期传播

2024-02-28 11:23:22

新型冠状病毒肺炎在中国武汉的早期传播（Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia）

期刊：《新英格兰医学杂志》
作者：来自中国疾控中心、各地疾控中心以及其他很多研究机构的研究者。
发表日期：2020.1.29
原文：NEJM-Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

译者注：由于译者水平有限，非专业英语或医学专业出身，翻译中可能存在错误，专业术语也可能并不准确，故留下原文以作对照，译文仅供参考。文章内容不代表译者观点，可信度请根据文章出处，作者身份，研究方法，数据来源，采样方法等由读者自行判断。希望能为想深入了解新型冠状病毒的每个人提供更多信息，因此不署名，欢迎转载。如有错误还望谅解，请评论指出以便更正。

摘要 Abstract

BACKGROUND
The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.
背景
2019年12月和2020年1月，中国湖北省武汉市发现了首例新型冠状病毒（2019-nCoV）引起的传染性肺炎（NCIP）的病例。我们研究了武汉的425宗确诊案例来推定传染性肺炎的流行病学特征。

METHODS
We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number.
方法
我们收集了2020年1月22日前的新型肺炎的人口特征，接触史和疾病时间线和实验室确诊病例。我们在本文中描述了这些病例的特征并估计了关键流行病学时延分布。在指数增长的早期，我们预估了疫情的倍增时间和基本传染数（R0）。

/*译者注：
R0值是指不考虑外力介入（例如实施防控措施），同时所有人都没有免疫力的情况，平均每个感染者把疾病传染给其它人的人数。也就是说，R0值越大，这个疾病的传播就越难控制。在没有实施防控的情况下，R0小于 1，意味着传染病将会逐渐消失。相对的，若 R0 大于 1，则传染病将以指数方式散播，成为流行病。
SARS的R0为0.85-3.（这数字是2003年的爆发时的统计则为0.85。由于该次爆发时实施严格隔离，因此这数字只代表该次爆发，而并非病症在不受限制之下的数字。在新加坡案例为3。）
流行性感冒的R0为2-3;天花的R0为5-7;埃博拉的R0为1.5-2.5。
因在疫情期间，对基本传染数的估计无可统一说法，多方估测的2019-nCov的R0指数从1.4-6.4不等，但都认为基本传染数（R0）>1。根据这一共识，在流行病学的定义下，新型冠状病毒疫情初期会以指数增长方式散布，成为流行病。
在疫情爆发初期，基本传染数据先前预计为1.4到2.5之间（另有香港中文大学研究认为新型冠状病毒肺炎基本传染数为3.30到5.47之间）。帝国理工学院根据截至2020年1月24日的数据，统计得出基本传染数中位数为2.6，95%置信区间为2.1-3.5。根据兰开斯特大学研究人员Jonathan M Read所领导的研究小组于2020年1月28日发表的预印本认为，此病毒的R0系数为3.11（95%置信度区间（95%CI）为2。39-4.13)，在武汉，此传染系数确定为5.0。而根据西安交通大学Tang Biao领导的研究小组与2020年1月24日所发表的文章认为：R0系数可能高达6.47。哈佛大学流行病学专家丁亮（Eric Ding）根据各方的公开信息，估计传染指数目前介于2.6与2.9之间。
基于至2020年1月22日的所有病例报告，中国疾控中心的研究者（*注：本文的作者们）认为R0系数应当为2.2，95%置信区间为1.4-3.9。
以上内容摘自wiki百科。
*/

RESULTS
Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).
结果
在最初确诊为新型肺炎的425名患者中，年龄的中位数为59岁，56%是男性。在2020年1月1日之前发病的大多数病例（占总数的55%）与华南海鲜市场有关，而随后的病例中仅有8.6%与华南海鲜市场有关。平均潜伏期为5.2天（95%置信区间，4.1-7.0），95%的分布为12.5天。在早期阶段，新型肺炎的规模约每7.4天翻一倍。它的平均连续间隔时间为7.5天（95%置信区间，5.3-19），基本传染数为2.2（95%置信区间，1.4-3.9）。
CONCLUSIONS
On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
结论
基于这些信息，有证据显示自2019年12月以来人传人已在亲密接触者之间发生。如有类似动态发生在其他地区，则需要付出巨大努力去减少该疾病的传播，以控制爆发。应当对高风险人群采取预防或减少传播的措施。（由*科学技术部及其他机构资助。）

Since December 2019, an increasing number of cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) have been identified in Wuhan, a large city of 11 million people in central China.On December 29, 2019, the first 4 cases reported, all linked to the Huanan (Southern China) Seafood Wholesale Market, were identified by local hospitals using a surveillance mechanism for “pneumonia of unknown etiology” that was established in the wake of the 2003 severe acute respiratory syndrome (SARS) outbreak with the aim of allowing timely identification of novel pathogens such as 2019-nCoV.In recent days, infections have been identified in other Chinese cities and in more than a dozen countries around the world.Here, we provide an analysis of data on the first 425 laboratory-confirmed cases in Wuhan to describe the epidemiologic characteristics and transmission dynamics of NCIP.
自从2019年12月以来在武汉（中国中部的一个拥有1100万人口的大城市）发现了越来越多的人被确诊为新型传染性肺炎。在2019年12月29日最初的4例确诊病例被报告，都与华南（中国南方）海鲜市场有关，由当地医院使用2003年的严重急性呼吸系统综合症（SARS）爆发后建立的“不明原因肺炎”监督机制进行鉴定，该机制的目的是为了及时确诊新型病症，例如2019-nCov。近期，在中国的其他城市以至全球十几个国家中陆续发现了感染病例。在此，我们提供我们对武汉的前425例实验室确证病例的数据的分析，以描述新型肺炎的流行病学特征和传播动态。

方法 Methods

SOURCES OF DATA
The earliest cases were identified through the “pneumonia of unknown etiology” surveillance mechanism.Pneumonia of unknown etiology is defined as an illness without a causative pathogen identified that fulfills the following criteria: fever (≥38°C), radiographic evidence of pneumonia, low or normal white-cell count or low lymphocyte count, and no symptomatic improvement after antimicrobial treatment for 3 to 5 days following standard clinical guidelines. In response to the identification of pneumonia cases and in an effort to increase the sensitivity for early detection, we developed a tailored surveillance protocol to identify potential cases on January 3, 2020, using the case definitions described below.Once a suspected case was identified, the joint field epidemiology team comprising members from the Chinese Center for Disease Control and Prevention (China CDC) together with provincial, local municipal CDCs and prefecture CDCs would be informed to initiate detailed field investigations and collect respiratory specimens for centralized testing at the National Institute for Viral Disease Control and Prevention, China CDC, in Beijing. A joint team comprising staff from China CDC and local CDCs conducted detailed field investigations for all suspected and confirmed 2019-nCoV cases.

Data were collected onto standardized forms through interviews of infected persons, relatives, close contacts, and health care workers. We collected information on the dates of illness onset, visits to clinical facilities, hospitalization, and clinical outcomes. Epidemiologic data were collected through interviews and field reports. Investigators interviewed each patient with infection and their relatives, where necessary, to determine exposure histories during the 2 weeks before the illness onset, including the dates, times, frequency, and patterns of exposures to any wild animals, especially those purportedly available in the Huanan Seafood Wholesale Market in Wuhan, or exposures to any relevant environments such as that specific market or other wet markets. Information about contact with others with similar symptoms was also included. All epidemiologic information collected during field investigations, including exposure history, timelines of events, and close contact identification, was cross-checked with information from multiple sources. Households and places known to have been visited by the patients in the 2 weeks before the onset of illness were also investigated to assess for possible animal and environmental exposures. Data were entered into a central database, in duplicate, and were verified with EpiData software (EpiData Association).
数据源
最早的病例由“不明原因肺炎”监督机制进行鉴定。不明原因肺炎被定义为一种没有确定的致病病因，但符合以下标准的疾病：发烧（≥38°C），有肺炎的放射性证据，低于或者有正常白细胞数或者淋巴细胞数，遵照标准临床指南进行抗菌治疗3至5天后无症状改善。为了识别肺炎病例，并致力于提高早期探测的敏度，我们量身定制了监督协议，用以下描述的病例定义识别在2020年1月3日的潜在病例。一旦发现疑似病例，将由中国疾病预防控制中心(CDC)，省，地方市级疾控中心和县级疾控中心组成的联合流行病学小组进行现场调查，并收集呼吸道标本，以便在国立病毒性疾病预防控制研究所——北京的中国疾病预防控制中心进行集中测试。由中国疾病预防控制中心和地方疾病预防控制中心工作人员组成的团队对所有疑似和确诊的2019-nCoV病例进行了详细的现场调查。

通过采访受感染者，家属，亲密接触者和医护人员，我们将数据整理为标准表格。我们收集了发病日期，临床就诊，住院治疗和临床结果的信息。流行病学数据则来自采访和现场报告。在必要时，研究人员采访了每位患者及其家属，以确定在发病的前两周的接触史，包括接触野生动物的日期，时间，频率和方式，尤其是那些在华南海鲜市场有的动物，或者接触过任何相关环境（例如特定市场或者其他海鲜市场）。这些信息中同样也包括他们是否曾与其他有类似症状的人接触过。所有这些现场调查时收集的流行病学信息（包括接触史，事件时间线和亲密接触者身份)都与多个来源的信息进行了交叉检查。还调查了已知的患者在发病前两周内曾去过的家庭和地方，以评估可能的动物和环境接触史。数据被一式两份输入*数据库，并通过EpiData软件（EpiData Association）进行验证。
CASE DEFINITIONS
The initial working case definitions for suspected NCIP were based on the SARS and Middle East respiratory syndrome (MERS) case definitions, as recommended by the World Health Organization (WHO) in 2003 and 2012.A suspected NCIP case was defined as a pneumonia that either fulfilled all the following four criteria — fever, with or without recorded temperature; radiographic evidence of pneumonia; low or normal white-cell count or low lymphocyte count; and no reduction in symptoms after antimicrobial treatment for 3 days, following standard clinical guidelines — or fulfilled the abovementioned first three criteria and had an epidemiologic link to the Huanan Seafood Wholesale Market or contact with other patients with similar symptoms. The epidemiologic criteria to define a suspected case were updated on January 18, 2020, once new information on identified cases became available. The criteria were the following: a travel history to Wuhan or direct contact with patients from Wuhan who had fever or respiratory symptoms, within 14 days before illness onset. A confirmed case was defined as a case with respiratory specimens that tested positive for the 2019-nCoV by at least one of the following three methods: isolation of 2019-nCoV or at least two positive results by real-time reverse-transcription–polymerase-chain-reaction (RT-PCR) assay for 2019-nCoV or a genetic sequence that matches 2019-nCoV.
病例定义
根据世界卫生组织（WHO）在2003年和2012年的建议，初始的新型肺炎的疑似病例的定义基于SARS和中东呼吸综合症（MERS）的病例定义来决定。新型肺炎的疑似病例被定义为满足以下四个标准的肺炎：发烧，有无体温记录；有肺炎的放射性证据；低于或者有正常白细胞数或者淋巴细胞数；抗菌治疗3天后症状没有减轻，遵循标准的临床指南-或满足上述的前三个标准，并且和华南海鲜市场有流行病学联系或者曾和其他有相似症状的患者接触。一旦获得了识别病例的新信息，定义疑似病例的流行病学标准会在2020年1月18日更新。确诊病例被定义为通过以下三种方法的至少一种方法对呼吸道标本进行2019-nCoV检测为阳性的病例：通过实时逆转录聚合酶链反应（RT-PCR）检测出2019-nCoV或匹配到2019-nCoV的基因序列，分离出2019-nCoV或至少获得两个阳性结果。
LABORATORY TESTING
The 2019-nCoV laboratory test assays were based on the previous WHO recommendation.Upper and lower respiratory tract specimens were obtained from patients. RNA was extracted and tested by real-time RT-PCR with 2019-nCoV–specific primers and probes. Tests were carried out in biosafety level 2 facilities at the Hubei (provincial) CDC and then at the National Institute for Viral Disease Control at China CDC. If two targets (open reading frame 1a or 1b, nucleocapsid protein) tested positive by specific real-time RT-PCR, the case would be considered to be laboratory-confirmed. A cycle threshold value (Ct-value) less than 37 was defined as a positive test, and a Ct-value of 40 or more was defined as a negative test. A medium load, defined as a Ct-value of 37 to less than 40, required confirmation by retesting. If the repeated Ct-value was less than 40 and an obvious peak was observed, or if the repeated Ct-value was less than 37, the retest was deemed positive. The genome was identified in samples of bronchoalveolar-lavage fluid from the patient by one of three methods: Sanger sequencing, Illumina sequencing, or nanopore sequencing. Respiratory specimens were inoculated in cells for viral isolation in enhanced biosafety laboratory 3 facilities at the China CDC.
实验室测试
2019-nCoV实验室测试方法是基于WHO先前的建议。从患者的上呼吸道和下呼吸道获取标本。提取RNA并使用2019-nCoV特异性引物和探针通过实时RT-PCR进行测试。测试是先在生物安全2级的湖北省疾控中心进行，然后在中国疾控中心的国家病毒疾病控制研究所进行的。如果两个靶标（开放阅读框1a或1b，核衣壳蛋白）通过特定的实时RT-PCR检测为阳性，则该病例被判定为实验室确诊。小于37的循环阈值（Ct值）被定义为阳性，大于或等于40的Ct值被定义为阴性。中等负载被定义为Ct值为37到40以下，此时需要通过重新测试进行确认。如果重新测试的Ct值小于40并且观察到明显的峰值，或者如果重新测试的Ct值小于37，则重新测试的结果会被判定为阳性。我们利用桑格测序，Illumina测序，纳米孔测序三种方法的其中一种，通过从患者的支气管肺泡灌洗液获得的样本来确定基因组。然后在中国疾病预防控制中心的增强型生物安全实验室3中，将呼吸道标本接种到细胞中进行病毒分离。

/*译者注：
开放阅读框（英语：Open reading frame；缩写：ORF；其他译名：开放阅读框架、开放读架等）是指在给定的阅读框架中，不包含终止密码子的一串序列。这段序列是生物个体的基因组中，可能作为蛋白质编码序列的部分。基因中的ORF包含并位于开始编码与终止编码之间。由于一段DNA或RNA序列有多种不同读取方式，因此可能同时存在许多不同的开放阅读框架。有一些计算机程序可分析出最有可能编码蛋白质的序列。
以上内容摘自wiki百科。
*/

STATISTICAL ANALYSIS
The epidemic curve was constructed by date of illness onset, and key dates relating to epidemic identification and control measures were overlaid to aid interpretation. Case characteristics were described, including demographic characteristics, exposures, and health care worker status. The incubation period distribution (i.e., the time delay from infection to illness onset) was estimated by fitting a log-normal distribution to data on exposure histories and onset dates in a subset of cases with detailed information available.Onset-to-first-medical-visit and onset-to-admission distributions were estimated by fitting a Weibull distribution on the dates of illness onset, first medical visit, and hospital admission in a subset of cases with detailed information available. We fitted a gamma distribution to data from cluster investigations to estimate the serial interval distribution, defined as the delay between illness onset dates in successive cases in chains of transmission.
We estimated the epidemic growth rate by analyzing data on the cases with illness onset between December 10 and January 4, because we expected the proportion of infections identified would increase soon after the formal announcement of the outbreak in Wuhan on December 31. We fitted a transmission model (formulated with the use of renewal equations) with zoonotic infections to onset dates that were not linked to the Huanan Seafood Wholesale Market, and we used this model to derive the epidemic growth rate, the epidemic doubling time, and the basic reproductive number (R0), which is defined as the expected number of additional cases that one case will generate, on average, over the course of its infectious period in an otherwise uninfected population. We used an informative prior distribution for the serial interval based on the serial interval of SARS with a mean of 8.4 and a standard deviation of 3.8.
Analyses of the incubation period, serial interval, growth rate, and R0 were performed with the use of MATLAB software (MathWorks). Other analyses were performed with the use of SAS software (SAS Institute) and R software (R Foundation for Statistical Computing).
统计分析
根据发病日期绘制了疫情曲线，并涵盖了与流行病鉴别和控制的措施有关的关键日期以帮助解释。描述了病例特征，包括人口统计学特征，接触情况和医护人员的状况。潜伏期分布（即从感染到发病的时间延迟）是通过对数正态分布拟合一部分病例的接触史和发病日期的数据来估算的，这些病例有详细的信息。发病到初次就诊和发病到住院的分布则是通过韦伯分布拟合一部分病例的发病日期，初次就诊，住院治疗来估算的，这些病例有详细的信息。我们对来自不同组的调查数据拟合了伽马分布来估计连续间隔分布（即传播链中连续病例中发病日期之间的延迟）。
我们通过分析12月10日至1月4日期间发病病例的数据来估算疫情的增长速率，因为我们预计在12月31日武汉疫情正式宣布之后，确定感染的比例会快速上升。我们使用人畜共患病的传染病模型拟合了传播模型（使用更新方程式来计算），来确定与华南海鲜批发市场无关的发病日期，并使用该模型得出疫情的增长速率，疫情倍增时间和基本传染数（R0，即在没有感染的人群中，一个病例在其传染期间平均会产生的额外病例的预期数目）。我们在 SARS的连续间隔时间（平均值为8.4，标准差为3.8）的基础上对2019-nCoV连续间隔时间进行了信息先验分布。
使用MATLAB软件（MathWorks）对潜伏期，连续间隔，增长速率和R0进行了分析。使用SAS软件（SAS Institute）和R软件（R Foundation for Statistical Computing）进行了其他分析。
ETHICS APPROVAL
Data collection and analysis of cases and close contacts were determined by the National Health Commission of the People’s * to be part of a continuing public health outbreak investigation and were thus considered exempt from institutional review board approval.
伦理批准
*国家卫生健康委员会决定对这些病例和亲密接触者们进行数据收集和分析，这是持续进行的对公共卫生疾病爆发调查的一部分，因此被认为无需机构审查委员会的批准。

结果 Results

The development of the epidemic follows an exponential growth in cases, and a decline in the most recent days is likely to be due to under-ascertainment of cases with recent onset and delayed identification and reporting rather than a true turning point in incidence (Figure 1). Specifically, the latter part of the curve does not indicate a decrease in the number of incident cases but is due to delayed case ascertainment at the cutoff date. Care should be taken in interpreting the speed of growth in cases in January, given an increase in the availability and use of testing kits as time has progressed. The majority of the earliest cases included reported exposure to the Huanan Seafood Wholesale Market, but there was an exponential increase in the number of nonlinked cases beginning in late December.
随着疫情发展，病例数呈指数增长，最近几天的下降可能是因为近期病例确诊不足以及疾病鉴别和报告的延迟，而并非发病率迎来了真正的转折(Figure 1)。特别是，曲线的后半部分并不代表疫情的病例数量的减少，而是由于截止日期之前病例确定的时间延迟。需要注意的是，当我们在分析一月份的病例增长速度时，应该考虑到随着时间的推移，检测试剂盒的可用性和使用量会增加。其中大多数早期病例据报道曾接触过华南海鲜市场，但从12月下旬开始，与华南海鲜市场无关的病例开始呈指数增长。

Figure 1. Onset of Illness among the First 425 Confirmed Cases of Novel Coronavirus (2019-nCoV)–Infected Pneumonia (NCIP) in Wuhan, China.
The decline in incidence after January 8 is likely to be due to delays in diagnosis and laboratory confirmation. China CDC denotes Chinese Center for Disease Control and Prevention, NHC National Health Commission of the People’s *, PCR polymerase chain reaction, WHC Wuhan Health Commission, and WHO World Health Organization.

Figure 1. 中国武汉肺炎最初的425名新型冠状病毒（2019-nCov）引起的传染性肺炎（NCIP）确诊病例的发病情况
1月8日之后的发病率下降可能是由于诊断和实验室确认的延迟。China CDC即中国疾病预防控制中心，NHC即*国家卫生健康委员会，PCR即聚合酶链式反应，WHC即武汉市卫生健康委员会，WHO即世界卫生组织。

The median age of the patients was 59 years (range, 15 to 89), and 240 of the 425 patients (56%) were male. There were no cases in children below 15 years of age. We examined characteristics of cases in three time periods: the first period was for patients with illness onset before January 1, which was the date the Huanan Seafood Wholesale Market was closed; the second period was for those with onset between January 1 and January 11, which was the date when RT-PCR reagents were provided to Wuhan; and the third period was those with illness onset on or after January 12 (Table 1). The patients with earlier onset were slightly younger, more likely to be male, and much more likely to report exposure to the Huanan Seafood Wholesale Market. The proportion of cases in health care workers gradually increased across the three periods (Table 1).
患者年龄的中位数为59岁（范围，15-89），425名患者中240人（56%）都是男性。没有一例儿童病例在15岁以下。我们研究了三个时间段病例的特征：第一个时间段的患者是在一月一日前发病的，这一天华南海鲜批发市场关闭了；第二个时间段的患者是在一月一日到一月十一日间发病的，这一天RT-PCR诊断试剂被送往武汉；第三个时间段的患者是在一月十二日之后发病的（Table 1）.早期发病的患者稍微年轻一些，大多是男性而且据报告曾接触过华南海鲜批发市场。在这三个时间段中，医护人员患者的比例随着推移逐渐增加。（Table 1）。

Table 1. Characteristics of Patients with Novel Coronavirus–Infected Pneumonia in Wuhan as of January 22, 2020.

Table 1. 到2020年1月22日为止武汉市新型冠状病毒感染肺炎患者的特征。
We examined data on exposures among 10 confirmed cases, and we estimated the mean incubation period to be 5.2 days (95% confidence interval [CI], 4.1 to 7.0); the 95th percentile of the distribution was 12.5 days (95% CI, 9.2 to 18) (Figure 2A). We obtained information on 5 clusters of cases, shown in Figure 3. On the basis of the dates of illness onset of 6 pairs of cases in these clusters, we estimated that the serial interval distribution had a mean (±SD) of 7.5±3.4 days (95% CI, 5.3 to 19) (Figure 2B).
我们研究了10个确诊病例的接触的数据，估计平均潜伏期为5.2天（95%置信区间[CI]，4.1-7.0）；分布的95%为12.5天。（95%置信区间，9.2-18）（Figure 2A）.我们获得了如Figure3所示的5组病例的信息。基于这些组的6对发病日期，我们估计平均连续间隔时间(±SD)为7.5±3.4（95%置信区间，95.3-19）(Figure 2B)。

Figure 2. Key Time-to-Event Distributions.
The estimated incubation period distribution (i.e., the time from infection to illness onset) is shown in Panel A. The estimated serial interval distribution (i.e., the time from illness onset in successive cases in a transmission chain) is shown in Panel B. The estimated distributions of times from illness onset to first medical visit are shown in Panel C. The estimated distributions of times from illness onset to hospital admission are shown in Panel D.

Figure 2. 关键时间事件分布
估计的潜伏期分布（即，从感染到发病的时间）显示在面板A中。估计的连续间隔分布（即，在传播链中从发病开始到出现连续病例的时间）显示在面板B中。从疾病发作到第一次就诊的估计时间显示在面板C中。从发病到住院的估计时间显示在面板D中。

In the epidemic curve up to January 4, 2020, the epidemic growth rate was 0.10 per day (95% CI, 0.050 to 0.16) and the doubling time was 7.4 days (95% CI, 4.2 to 14). Using the serial interval distribution above, we estimated that R0 was 2.2 (95% CI, 1.4 to 3.9).
在截至2020年1月4日的疫情曲线中，疫情增长速率为每天0.10（95％置信区间，0.050-0.16），而疫情倍增时间为7.4天（95％置信区间，4.2-14）。使用上面的连续间隔分布，我们估计R0为2.2（95％置信区间，1.4-3.9）。
The duration from illness onset to first medical visit for 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days (95% CI, 4.3 to 7.5), which was similar to that for 207 patients with illness onset between January 1 and January 11, with a mean of 4.6 days (95% CI, 4.1 to 5.1) (Figure 2C). The mean duration from onset to hospital admission was estimated to be 12.5 days (95% CI, 10.3 to 14.8) among 44 cases with illness onset before January 1, which was longer than that among 189 patients with illness onset between January 1 and 11 (mean, 9.1 days; 95% CI, 8.6 to 9.7) (Figure 2D). We did not plot these distributions for patients with onset on or after January 12, because those with recent onset and longer durations to presentation would not yet have been detected.
1月1日之前发病的45名患者从发病到首次就诊的持续时间估计平均时间为5.8天（95％置信区间，4.3-7.5），与1月1日到1月11日之间的207名发病的患者相似，这些患者从发病到首次就诊的持续时间估计平均时间为4.6天（95％CI，4.1至5.1）（Figure 2C）。在1月1日之前发病的44例患者中，从发病到入院的平均持续时间估计为12.5天（95％置信区间，10.3-14.8），比1月1日至11日之间的189例发病的平均时间更长（平均9.1天； 95％置信区间，8.6-9.7）（Figure 2D）。我们并没有为1月12日及之后发病的患者绘制这些分布图，因为还没有发现那些近期发病且病程较长的患者。

Figure 3. Detailed Information on Exposures and Dates of Illness Onset in Five Clusters Including 16 Cases.
Numbers in boxes are calendar dates in December 2019 and January 2020. Data from the 5 secondary cases (patients who had clear exposure to only one index case and had no other potential source of infection) were used to estimate the serial interval distribution. The first four clusters were identified in Wuhan, and the fifth cluster was identified in Huanggang.

Figure 3. 在五组中包括16例病例的接触和发病日期的详细信息。
框中的数字是2019年12月和2020年1月的日历日期。使用5例继发病例(患者仅亲密接触过一个起始病例并且没有其他潜在感染源)被用来评估连续间隔分布。在武汉确定了前四组，在黄冈确定了第五组。

结论 Discussion

Here we provide an initial assessment of the transmission dynamics and epidemiologic characteristics of NCIP. Although the majority of the earliest cases were linked to the Huanan Seafood Wholesale Market and the patients could have been infected through zoonotic or environmental exposures, it is now clear that human-to-human transmission has been occurring and that the epidemic has been gradually growing in recent weeks. Our findings provide important parameters for further analyses, including evaluations of the impact of control measures and predictions of the future spread of infection.
在这里，我们对新型肺炎的传播和流行病学特征进行了初步的评估。尽管大多数最早的病例与华南海鲜批发市场有关，并且患者可能是通过接触动物或环境而感染的，但现在明显的人传人已经发生，而且这种传染病在最近几周正在逐步蔓延。我们的发现为进一步分析提供了重要参数，包括评估控制措施的影响以及对未来传染扩散的预测。
We estimated an R0 of approximately 2.2, meaning that on average each patient has been spreading infection to 2.2 other people. In general, an epidemic will increase as long as R0 is greater than 1, and control measures aim to reduce the reproductive number to less than 1. The R0 of SARS was estimated to be around 3, and SARS outbreaks were successfully controlled by isolation of patients and careful infection control.In the case of NCIP, challenges to control include the apparent presence of many mild infections and limited resources for isolation of cases and quarantine of their close contacts. Our estimate of R0 was limited to the period up to January 4 because increases in awareness of the outbreak and greater availability and use of tests in more recent weeks will have increased the proportions of infections ascertained. It is possible that subsequent control measures in Wuhan, and more recently elsewhere in the country as well as overseas, have reduced transmissibility, but the detection of an increasing number of cases in other domestic locations and around the world suggest that the epidemic has continued to increase in size. Although the population quarantine of Wuhan and neighboring cities since January 23 should reduce the exportation of cases to the rest of the country and overseas, it is now a priority to determine whether local transmission at a similar intensity is occurring in other locations.
我们估计R0约为2.2，这意味着平均每个患者会传染2.2人。一般来说，只要R0大于1，就会扩展成为流行病，所以采取控制措施的目标是将基本传染数降低到1以下。SARS的R0约为3左右，当时通过隔离患者以及仔细的传染控制成功地控制了SARS的爆发。此次新型肺炎面临的挑战包括明显存在许多轻度感染以及隔离患者及其亲密接触者的资源有限。我们估计的R0仅适用于到1月4日为止的情况，因为人们对疫情的意识增强以及最近几周测试的可用性和使用频率的提高将增加感染确定的比例。武汉市及其他国家以及海外最近采取的后续控制措施很可能已经降低了传染能力, 但国内其他地区和世界范围内发现的病例数量还在不断增加，这表明该传染病的规模仍在持续扩大。尽管1月23日开始的武汉及其周边城市的人口检疫将减少向全国其他地区以及海外输出病例，但首先应该确定同等强度的传播是否已经在其他地区本地发生。

It is notable that few of the early cases occurred in children, and almost half the 425 cases were in adults 60 years of age or older, although our case definition specified severe enough illness to require medical attention, which may vary according to the presence of coexisting conditions. Furthermore, children might be less likely to become infected or, if infected, may show milder symptoms, and either of these situations would account for underrepresentation in the confirmed case count. Serosurveys after the first wave of the epidemic would clarify this question. Although infections in health care workers have been detected, the proportion has not been as high as during the SARS and MERS outbreaks.One of the features of SARS and MERS outbreaks is heterogeneity in transmissibility, and in particular the occurrence of super-spreading events, particularly in hospitals.Super-spreading events have not yet been identified for NCIP, but they could become a feature as the epidemic progresses.
值得注意的是，早期病例中很少有儿童，425例病例中几乎半数以上都是60岁或以上的成年人，虽然我们在病例定义中指出疾病严重到一定程度就需要医疗救治，但具体情况还是要根据不同的共存条件（*注：共存条件即需要同时满足的两个或多个条件）而定。此外，也许儿童被感染的可能性小一些，或者他们如果被感染，会表现出更轻的症状，但在确诊病例数中，以上两种情况都没有足够的代表性。第一波疫情流行之后的血清调查将澄清这个问题。尽管已经发现医护人员感染，但这一比例并没有SARS和MERS爆发时高。SARS和MERS爆发的特征之一是传染异质性，尤其超级传播事件的发生，特别是在医院。目前还没有确认发现新型肺炎的超级传播事件，但随着疫情发展，这些事件将成为一个特征。

Although delays between the onset of illness and seeking medical attention were generally short, with 27% of patients seeking attention within 2 days after onset, delays to hospitalization were much longer, with 89% of patients not being hospitalized until at least day 5 of illness (Figure 2). This indicates the difficulty in identifying and isolating cases at an earlier stage of disease. It may be necessary to commit considerable resources to testing in outpatient clinics and emergency departments for proactive case finding, both as part of the containment strategy in locations without local spread yet as well as to permit earlier clinical management of cases. Such an approach would also provide important information on the subclinical infections for a better assessment of severity.
尽管发病和寻求医疗救助之间的时延通常很短，有27％的患者在发病后2天内就诊，但到住院的时延要长得多，有89％的患者至少要等到发病第5天才能住院（图2）。这表明在疾病的早期阶段难以识别和隔离病例。可能需要投入大量资源在门诊诊所和急诊科进行检测来主动发现病例，这些都是在没有局部扩散的地区进行的遏制策略的一部分，它使得更早地进行病例管理成为可能。这种方法还将提供有关亚临床感染的重要信息，从而更好地评估疫情严重程度。

Our preliminary estimate of the incubation period distribution provides important evidence to support a 14-day medical observation period or quarantine for exposed persons. Our estimate was based on information from 10 cases and is somewhat imprecise; it would be important for further studies to provide more information on this distribution. When more data become available on epidemiologic characteristics of NCIP, a detailed comparison with the corresponding characteristics of SARS and MERS, as well as the four coronaviruses endemic in humans, would be informative.
我们对潜伏期分布的初步估计提供了重要的证据来支持对接触者进行14天的医学观察或隔离。我们的估算仅基于10个案例的信息，因此可能不太准确；进一步研究提供此分布的更多信息是非常重要的。当获得新型肺炎的更多流行病学特征的数据时，与SARS和MERS以及人类中流行的4中冠状病毒的相应特征进行比较，将会获得更多信息。

Our study suffers from the usual limitations of initial investigations of infections with an emerging novel pathogen, particularly during the earliest phase, when little is known about any aspect of the outbreak and there is a lack of diagnostic reagents. To increase the sensitivity for early detection and diagnosis, epidemiology history was considered in the case identification and has been continually modified once more information has become available. Confirmed cases could more easily be identified after the PCR diagnostic reagents were made available to Wuhan on January 11, which helped us shorten the time for case confirmation. Furthermore, the initial focus of case detection was on patients with pneumonia, but we now understand that some patients can present with gastrointestinal symptoms, and an asymptomatic infection in a child has also been reported.Early infections with atypical presentations may have been missed, and it is likely that infections of mild clinical severity have been under-ascertained among the confirmed cases.We did not have detailed information on disease severity for inclusion in this analysis.
我们的研究遇到了对新出现的新型病原体感染的初步调查，尤其是在早期阶段，通常存在的局限性，这时对疫情的各方面都知之甚少，并且缺少诊断试剂。为了提高早期发现和诊断的敏度，我们考虑了病例鉴别的流行病学历史，一旦获得更多信息，就不断对其进行修改。在1月11日向武汉提供PCR诊断试剂后，确诊病例变得更简单了，这有助于我们缩短确诊病例的时间。此外，病例检测的最初重点是肺炎患者，但我们现在了解到一些患者还存在胃肠道症状，有非典型症状的早期感染者可能被漏掉了，并且在确诊病例中，轻度感染的严重程度很可能不确定。在本次的分析中，我们没有详细的信息来对疾病的严重程度做出结论。

In conclusion, we found that cases of NCIP have been doubling in size approximately every 7.4 days in Wuhan at this stage. Human-to-human transmission among close contacts has occurred since the middle of December and spread out gradually within a month after that. Urgent next steps include identifying the most effective control measures to reduce transmission in the community. The working case definitions may need to be refined as more is learned about the epidemiologic characteristics and outbreak dynamics. The characteristics of cases should continue to be monitored to identify any changes in epidemiology — for example, increases in infections among persons in younger age groups or health care workers. Future studies could include forecasts of the epidemic dynamics and special studies of person-to-person transmission in households or other locations, and serosurveys to determine the incidence of the subclinical infections would be valuable.These initial inferences have been made on a “line list” that includes detailed individual information on each confirmed case, but there may soon be too many cases to sustain this approach to surveillance, and other approaches may be required.
总之，我们发现在此阶段，大约每7.4天武汉的新型肺炎的病例数就翻一倍。自12月中旬以来，人传人就已经在亲密接触者之间发生，并在随后的一个月内逐渐传播开来。下一步最紧急要做的事就是确定减少社区传播最有效的控制措施。随着了解更多的流行病学特征和爆发动态，可能需要完善现行的病例定义。应继续监测病例特征，以发现所有流行病学的变化，例如，年龄较小的人群或医护人员中感染人数的增加。未来的研究可能包括对流行趋势的预测，对家庭或其他地方人传人的特定研究，以及用血清调查来确定亚临床感染的发生概率，这些研究将是有价值的。这些初步推断都是在“line list”上进行的，其中包括每个确诊病例的详细个人信息，但是可能很快就会有太多病例以至于我们无法维持这种观察方式，可能还需要其他方法。

Supported by the Ministry of Science and Technology of China, the National Science and Technology Major Projects of China (2018ZX10201-002-008-002, 2018ZX10101002-003), the China–U.S. Collaborative Program on Emerging and Re-emerging Infectious Disease, and National Mega-Projects for Infectious Disease (2018ZX10201002-008-002), the National Natural Science Foundation (71934002), the National Institute of Allergy and Infectious Diseases (Centers of Excellence for Influenza Research and Surveillance [CEIRS] contract number HHSN272201400006C), and the Health and Medical Research Fund (*). None of the funders had any role in the study design and the collection, analysis, and interpretation of data or in the writing of the article and the decision to submit it for publication. The researchers confirm their independence from funders and sponsors.
由中国科学技术部, 国家科技重大专项 (2018ZX10201-002-008-002, 2018ZX10101002-003), 中美新出现和再出现的传染病合作计划, 国家重大传染病项目 (2018ZX10201002-008-002), 国家自然科学基金会 (71934002), 国立过敏与传染病研究所 (流感研究和监测卓越中心 [CEIRS] 合同号 HHSN272201400006C), 以及健康与医学研究基金会（香港）赞助。资助者在研究设计，数据的收集，分析，解释数据，撰写文章以及在将其提交发表的决定中没有起任何作用。研究人员证实他们独立于资助者和赞助者。

Drs. Q. Li, X. Guan, P. Wu, and X. Wang and Drs. B. Cowling, B. Yang, M. Leung, and Z. Feng contributed equally to this article.
Drs. Q. Li, X. Guan, P. Wu, and X. Wang and Drs. B. Cowling, B. Yang, M. Leung, and Z. Feng对本文做出了同等的贡献。

The views expressed in this article are those of the authors and do not represent the official policy of the China CDC. All the authors have declared no relationships or activities that could appear to have influenced this work.
本文表达的观点仅代表作者们的个人观点，并不代表中国疾病预防控制中心的官*策。作者们都宣称没有任何关系或活动可能对这项工作产生影响。

This article was published on January 29, 2020, and last updated on January 31, 2020, at NEJM.org.
本文发布于2020年1月29日，最后更新于2020年1月31日，NEJM.org。

We thank Wuhan CDC, Huanggang CDC, and other prefecture CDCs and medical institutions in Wuhan for assistance with field investigation administration and data collection and the National Institute for Viral Disease Control and Prevention, China CDC, for assistance with laboratory testing.
我们感谢武汉市疾病预防控制中心，黄冈疾病预防控制中心以及武汉市其他县级疾病预防控制中心和医疗机构在现场调查管理和数据收集方面的帮助，并感谢中国疾病预防控制中心的国家病毒性疾病预防控制中心在实验室检测方面的帮助。

作者单位 Author Affiliations

From the Chinese Center for Disease Control and Prevention, Beijing (Q.L., X.W., L.Z., R.R., N.X., C.L., D.L., J.Z., W.T., L.J., Q.W., R.W., Y.Z., G. Shi, G.F.G., Z.F.), the Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei (X.G., Y.T., X.X., Y.W., Q.C., M.L., C.C., R.Y., S.Z., Y. Luo, B.Y.), the World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, University of *, * (P.W., K.S.M.L., E.H.Y.L., J.Y.W., T.T.Y.L., J.T.W., B.J.C., G.M.L.), the Chinese Field Epidemiology Training Program, Chinese Center for Disease Control and Prevention, Beijing (T.L., R.Y., S.Z., H. Liu, Y. Liu, G. Shao, H. Li, Z.T.), the Jingzhou Center for Disease Control and Prevention, Jingzhou, Hubei (T.L.), the Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan (H. Liu); the Hunan Provincial Center for Disease Control and Prevention, Changsha, Hunan (Y. Liu), the Anyang Municipal Center for Disease Control and Prevention, Anyang, Henan (G. Shao), the Panjin Center for Disease Control and Prevention, Panjin, Liaoning (H. Li), the Guizhou Center for Disease Control and Prevention, Guiyang, Guizhou (Z.T.), the Jiading District Center for Disease Control and Prevention, Shanghai (Y.Y.), the Nanchang Center for Disease Control and Prevention, Nanchang, Jiangxi (Z.D.), the Inner * Comprehensive Center for Disease Control and Prevention, Hohhot, Inner * (B.L.), and the Baoshan District Center for Disease Control and Prevention, Shanghai (Z.M.) — all in China.

Address reprint requests to Dr. Feng at the Chinese Center for Disease Control and Prevention, No. 155 Changbai Rd., Changping District, Beijing, China, or at fengzj@chinacdc.cn; to Dr. G.M. Leung or Dr. Cowling at the School of Public Health, Li Ka Shing Faculty of Medicine, University of *, 21 Sassoon Rd., Pokfulam, *, China, or at gmleung@hku.hk or bcowling@hku.hk, respectively; or to Dr. B. Yang at the Hubei Center for Disease Control and Prevention, No. 35 Zhuodaoquan North Rd., Hongshan District, Wuhan, Hubei, China, or at 49205957@qq.com.
略

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引用文献 Citing Article

Joseph T Wu, Kathy Leung, Gabriel M Leung. (2020) Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. The Lancet.
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