SOURCES OF DATA
The earliest cases were identified through the “pneumonia of unknown etiology” surveillance mechanism.4 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.1 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).
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 2012.6-8 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.9 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.
LABORATORY TESTINGThe 2019-nCoV laboratory test assays were based on the previous WHO recommendation.10Upper 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.3
STATISTICAL ANALYSISThe 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 3.8.11
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).
ETHICS APPROVAL
Data collection and analysis of cases and close contacts were determined by the National Health Commission of the People’s Republic of China to be part of a continuing public health outbreak investigation and were thus considered exempt from institutional review board approval.