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Science Abb3221 Full PDF
Science Abb3221 Full PDF
Science Abb3221 Full PDF
London W2 1PG, UK. 2Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. 3Department of
Land, Air and Water Resources, University of California, Davis, Davis, CA 95616, USA. 4Department of Urban Planning and Design, The University of Hong Kong, Hong Kong.
5Ministry of Education Key Laboratory for Earth System Modeling, Department of Earth System Science, Tsinghua University, Beijing 10084, P. R. China. 6Department of
Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
*These authors contributed equally to this work.
†Corresponding author. Email: sp3449@cumc.columbia.edu (S.P.); jls106@cumc.columbia.edu (J.S.)
The novel coronavirus that emerged in Wuhan, China (SARS- infected individuals; and μβ, the transmission rate due to un-
CoV2) at the end of 2019 quickly spread to all Chinese prov- documented individuals, which is β reduced by a factor μ.
inces and, as of 1 March 2020, to 58 other countries (1, 2). Spatial spread of SARS-CoV2 across cities is captured by
Efforts to contain the virus are ongoing; however, given the the daily number of people traveling from city j to city i and
many uncertainties regarding pathogen transmissibility and a multiplicative factor. Specifically, daily numbers of travel-
virulence, the effectiveness of these efforts is unknown. ers between 375 Chinese cities during the Spring Festival pe-
The fraction of undocumented but infectious cases is a riod (“Chunyun”) were derived from human mobility data
critical epidemiological characteristic that modulates the collected by the Tencent Location-based Service during the
pandemic potential of an emergent respiratory virus (3–6). 2018 Chunyun period (1 February–12 March 2018) (7). Chun-
These undocumented infections often experience mild, lim- yun is a period of 40 days—15 days before and 25 days after
ited or no symptoms and hence go unrecognized, and, de- the Lunar New Year—during which there are high rates of
pending on their contagiousness and numbers, can expose a travel within China. To estimate human mobility during the
far greater portion of the population to virus than would oth- 2020 Chunyun period, which began 10 January, we aligned
erwise occur. Here, to assess the full epidemic potential of the 2018 Tencent data based on relative timing to the Spring
SARS-CoV2, we use a model-inference framework to estimate Festival. For example, we used mobility data from 1 February
the contagiousness and proportion of undocumented infec- 2018 to represent human movement on 10 January 2020, as
tions in China during the weeks before and after the shut- these days were similarly distant from the Lunar New Year.
down of travel in and out of Wuhan. During the 2018 Chunyun, a total of 1.73 billion travel events
We developed a mathematical model that simulates the were captured in the Tencent data; whereas 2.97 billion trips
spatiotemporal dynamics of infections among 375 Chinese are reported (7). To compensate for underreporting and rec-
cities (see supplementary materials). In the model, we di- oncile these two numbers, a travel multiplicative factor, θ,
vided infections into two classes: (i) documented infected in- which is greater than 1, is included (see supplementary mate-
dividuals with symptoms severe enough to be confirmed, i.e., rials).
observed infections; and (ii) undocumented infected individ- To infer SARS-CoV2 transmission dynamics during the
uals. These two classes of infection have separate rates of early stage of the outbreak, we simulated observations during
transmission: β, the transmission rate due to documented 10–23 January 2020 (i.e., the period before the initiation of
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travel restrictions, fig. S1) using an iterated filter-ensemble CI: 2.04−2.77), indicating a high capacity for sustained trans-
adjustment Kalman filter (IF-EAKF) framework (8–10). With mission of COVID-19 (Table 1 and Fig. 1D). This finding aligns
this combined model-inference system, we estimated the tra- with other recent estimates of the reproductive number for
jectories of four model state variables (Si, Ei, I ir , I iu : the sus- this time period (6, 11–15). In addition, the median estimates
ceptible, exposed, documented infected, and undocumented for the latent and infectious periods are approximately 3.69
infected sub-populations in city i) for each of the 375 cities, and 3.48 days, respectively. We also find that, during 10–23
while simultaneously inferring six model parameters (Z, D, μ, January, only 14% (95% CI: 10–18%) of total infections in
β, α, θ: the average latent period, the average duration of in- China were reported. This estimate reveals a very high rate of
fection, the transmission reduction factor for undocumented undocumented infections: 86%. This finding is inde-
infections, the transmission rate for documented infections; pendently corroborated by the infection rate among foreign
the fraction of documented infections, and the travel multi- nationals evacuated from Wuhan (see supplementary materi-
plicative factor). als). These undocumented infections are estimated to have
Details of model initialization, including the initial seed- been half as contagious per individual as reported infections
ing of exposed and undocumented infections, are provided in (μ = 0.55; 95% CI: 0.46–0.62). Other model fittings made us-
ing alternate values of Td and Seedmax or different distribu-
First release: 16 March 2020 www.sciencemag.org (Page numbers not final at time of first release) 2
more available rapid testing for infection confirmation (11, of the total force of infection was mediated through these un-
12). These measures along with changes in medical care-seek- documented infections (Table 1). This high proportion of un-
ing behavior due to increased awareness of the virus and in- documented infections, many of whom were likely not
creased personal protective behavior (e.g., wearing of severely symptomatic, appears to have facilitated the rapid
facemasks, social distancing, self-isolation when sick), likely spread of the virus throughout China. Indeed, suppression of
altered the epidemiological characteristics of the outbreak af- the infectiousness of these undocumented cases in model
ter 23 January. To quantify these differences, we re-estimated simulations reduces the total number of documented cases
the system parameters using the model-inference framework and the overall spread of SARS-CoV2 (Fig. 2). In addition, the
and city-level daily cases reported between 24 January and 8 best-fitting model has a reporting delay of 9 days from initial
February. As inter-city mobility was restricted after 23 Janu- infectiousness to confirmation; in contrast line-list data for
ary, we tested two altered travel scenarios: the same 10–23 January period indicates an average 6.6 day
(i) scenario 1: a 98% reduction of travel in and out of Wuhan delay from initial manifestation of symptoms to confirmation
and an 80% reduction of travel between all other cities, as (17). This discrepancy suggests pre-symptomatic shedding
indicated by changes in the Baidu Mobility Index (16) (table may be typical among documented infections. The relative
S2); and (ii) scenario 2: a complete stoppage of inter-city timing of viremia and shedding onset and peak versus symp-
First release: 16 March 2020 www.sciencemag.org (Page numbers not final at time of first release) 3
rebound outbreak once control measures are relaxed is un- 10. S. Pei, F. Morone, F. Liljeros, H. Makse, J. L. Shaman, Inference and control of the
clear. Further, similar control measures and travel re- nosocomial transmission of methicillin-resistant Staphylococcus aureus. eLife 7,
e40977 (2018). doi:10.7554/eLife.40977 Medline
strictions would have to be implemented outside China to 11. Health Commission of Hubei Province, The 8th Press Conference on the Prevention
prevent reintroduction of the virus. and Control of COVID-19;
The results for 10–23 January 2020 delineate the charac- http://wjw.hubei.gov.cn/fbjd/dtyw/202001/t20200130_2016544.shtml.
teristics of the SARS-CoV2 moving through a developed soci- 12. Health Commission of Hubei Province, The 9th Press Conference on the
Prevention and Control of COVID-19;
ety, China, without major restrictions or control. These http://wjw.hubei.gov.cn/fbjd/dtyw/202001/t20200131_2017018.shtml.
findings provide a baseline assessment of the fraction of un- 13. J. T. Wu, K. Leung, G. M. Leung, Nowcasting and forecasting the potential domestic
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mented and that, per person, these undocumented infections Medline
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First release: 16 March 2020 www.sciencemag.org (Page numbers not final at time of first release) 5
Table 1. Best-fit model posterior estimates of key epidemiological
parameters for simulation with the full metapopulation model during
10–23 January 2020 (Seedmax = 2000, Td = 9 days).
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Fig. 1. Best-fit model and sensitivity analysis. Simulation of daily reported cases in all cities (A), Wuhan city (B)
and Hubei province (C). The blue box and whiskers show the median, interquartile range, and 95% credible
intervals derived from 300 simulations using the best-fit model (Table 1). The red x’s are daily reported cases.
The distribution of estimated Re is shown in (D). The impact of varying α and μ on Re with all other parameters
held constant at Table 1 mean values (E). The black solid line indicates parameter combinations of (α,μ) yielding
Re = 2.38. The estimated parameter combination α = 0.14 and μ = 0.55 is shown by the red x; the dashed box
indicates the 95% credible interval of that estimate. Log-likelihood for simulations with combinations of (α,μ)
and all other parameters held constant at Table 1 mean values (F). For each parameter combination, 300
simulations were performed. The best-fit estimated parameter combination α = 0.14 and μ = 0.55 is shown by
the red x (note that the x is plotted at the lower left corner of its respective heat map pixel, i.e., the pixel with the
highest log likelihood); the dashed box indicates the 95% credible interval of that estimate.
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Fig. 2. Impact of undocumented infections on the transmission of SARS-CoV2. Simulations generated using
the parameters reported in Table 1 with μ = 0.55 (red) and μ = 0 (blue) showing daily documented cases in all
cities (A), daily documented cases in Wuhan city (B) and the number of cities with ≥ 10 cumulative documented
cases (C). The box and whiskers show the median, interquartile range, and 95% credible intervals derived from
300 simulations.
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Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus
(SARS-CoV2)
Ruiyun Li, Sen Pei, Bin Chen, Yimeng Song, Tao Zhang, Wan Yang and Jeffrey Shaman
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