EARLY TRANSMISSION DYNAMICS OF NCIP distrns were case was defined as a case with resniratory medical visit and ho spital admission in a subse mens that tested positive for the 2019-nCov by at of cases with detailed information available.We least one of the following three methods:isola-fitted a gamma distribution to data from cluster tion of 2019-nCov or at least two positive results inve stigations to estimate the serial interval dis by real-tim reverse-transcriptio -polymera tribut n,defined as the delay betv een ilnes cham-e CR)assay or Cov or onset dates in successive cases in chains of tran genet We estimated the owth rate by LABORATORY TESTING ases with illness onse The 2019-nCoV laboratory test ass ys were based between December 10 and January 4,because we on the previous WHO recommendation.Uppe expected the proportion of infections identified er respiratory tra specimens were ob would in crease soon after the formal announce ron ract an outbrea er real-tin with in Wuhan on De 2019-n e fitte in b pri set dates that w ot linked to the Huanan seafood wholesale market and we for viral Disease Control at China CDC.If two used this model to derive the epidemic growth targets (open reading frame la or 1b,nucleocap rate,the epidemic doubling time,and the basic e by spec ic real-tim number (R),whi n is defined as cas the ex cted numbe r of s that on (less than 3 was defin a its infe test,and a Ct-value of 40 or mo vas defined a ulation We used an info ior dist a negative test.A medium load,defined as a Ctvalue bution for the serial interval based on the serial of 37 to less than 40,required confirmation by interval of SARS with a mean of 8.4 and a stan- d Ct-value was less dard c ation of 3.8.' an obvious pea s than 37th d,or if Analyse tion period,s an . Th of bro the patient by one of three methods:Sange se. quencing,Illumina sequencing,or nanopore se- dation for Statistical Computing). quencing.Respiratory specimens were inocula e C d biosafety ETHICS ata collectio and ana sis of es and conacts were c fthe pec The epidemic curve was constructed by date of be part of a continuing public health outbreak illness onset and key dates relatine to epidemi investigation and were thus considered exempt identification and control measures were overlaid from institutional review board approval to aid int erpretation. Case characteristics were described,inc g c mographic chara RESULTS me The deve tion to illnes lopmen of the epidemic follow tia h in nd a de fitting a log-normal distribution to data on e most recent days is likely to he due to under posure histories and onset dates in a subset of ascertainment of cases with recent onset and cases with c tailed information available.Onse delayed identification and r orting rather than to-first-medical-visit and onset-to-admission dis a true turning point in incidence(Fig 1).Spe N ENGLIMED NEIM.OR Downloaded from nejm.og at SOUTHERN MEDICAL UNIVERSITY h6,2020.F opyngnt 2020 Nn engl j med nejm.org 3 Early Transmission Dynamics of NCIP Wuhan who had fever or respiratory symptoms, within 14 days before illness onset.9 A confirmed case was defined as a case with respiratory speci￾mens that tested positive for the 2019-nCoV by at least one of the following three methods: isola￾tion 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 Testing The 2019-nCoV laboratory test assays were based on the previous WHO recommendation.10 Upper and lower respiratory tract specimens were ob￾tained from patients. RNA was extracted and tested by real-time RT-PCR with 2019-nCoV–spe￾cific primers and probes. Tests were carried out in biosafety level 2 facilities at the Hubei (pro￾vincial) CDC and then at the National Institute for Viral Disease Control at China CDC. If two targets (open reading frame 1a or 1b, nucleocap￾sid 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 se￾quencing, Illumina sequencing, or nanopore se￾quencing. Respiratory specimens were inoculat￾ed in cells for viral isolation in enhanced biosafety laboratory 3 facilities at the China CDC.3 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 ex￾posure histories and onset dates in a subset of cases with detailed information available. Onset￾to-first-medical-visit and onset-to-admission dis￾tributions 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 dis￾tribution, defined as the delay between illness onset dates in successive cases in chains of trans￾mission. 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 announce￾ment of the outbreak in Wuhan on December 31. We fitted a transmission model (formulated with the use of renewal equations) with zoonotic in￾fections 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 distri￾bution for the serial interval based on the serial interval of SARS with a mean of 8.4 and a stan￾dard deviation of 3.8.11 Analyses of the incubation period, serial in￾terval, 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 Foun￾dation 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. Results The development of the epidemic follows an ex￾ponential 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 (Fig. 1). Spe￾The New England Journal of Medicine Downloaded from nejm.org at SOUTHERN MEDICAL UNIVERSITY on March 6, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved