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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.
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.
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.17 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.18 We did not have detailed information on disease severity for inclusion in this analysis.
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.14 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.19
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 (Hong Kong). 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.
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.
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.
This article was published on January 29, 2020, and last updated on January 30, 2020, at 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.
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