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      Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19)

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          Abstract

          The number of novel coronavirus (COVID-19) cases worldwide continues to grow, and the gap between reports from China and statistical estimates of incidence based on cases diagnosed outside China indicates that a substantial number of cases are underdiagnosed (Nishiura et al., 2020a). Estimation of the asymptomatic ratio—the percentage of carriers with no symptoms—will improve understanding of COVID-19 transmission and the spectrum of disease it causes, providing insight into epidemic spread. Although the asymptomatic ratio is conventionally estimated using seroepidemiological data (Carrat et al., 2008, Hsieh et al., 2014), the collection of these data requires significant logistical effort, time, and cost. Instead, we propose a method of estimating the asymptomatic ratio by using information on Japanese nationals who were evacuated from Wuhan, China on charter flights. Figure 1 illustrates the flow of the evacuation process. By February 6, 2020 a total of N = 565 citizens had been evacuated. Among them, pN = 63 (11.2%) were considered symptomatic upon arrival based on (1) temperature screening before disembarkation, and (2) face-to-face interviews eliciting information on symptoms including fever, cough, and other non-specific symptoms consistent with COVID-19. Reverse transcription PCR (RT-PCR) testing was performed for all passengers, and m = 4 asymptomatic and n = 9 symptomatic passengers tested positive for COVID-19. Figure 1 Flow diagram of symptom screening and viral testing for passengers on chartered evacuation flights from Wuhan, China to Japan. The flow of Japanese residents evacuating from Wuhan and screened in Japan. A total of N passengers were evaluated, of whom a fraction p were symptomatic upon arrival. Among symptomatic and asymptomatic individuals, n and m persons, respectively, tested positive for the virus by RT-PCR. Figure 1 Employing a Bayes theorem, the asymptomatic ratio is defined as P r ( a s y m p t o m a t i c   |   i n f e c t i o n ) = Pr i n f e c t i o n   |   a s y m p t o m a t i c P r ( a s y m p t o m a t i c ) P r ( i n f e c t i o n ) , which can be calculated as m/(n + m), as seen in Figure 1. Using a binomial distribution, the asymptomatic ratio among evacuees was thus estimated to be 30.8% (95% confidence interval 7.7–53.8%). On March 6, 2020, a minimum of 30 days had elapsed since the citizens had departed from Wuhan – a length of observation sufficiently longer than the COVID-19 incubation period (Li et al., 2020, Linton et al., 2020). Thus, there was very little probability that the four virus-positive asymptomatic individuals would develop symptoms. In general, asymptomatic infections cannot be recognized if they are not confirmed by RT-PCR or other laboratory testing, and symptomatic cases may not be detected if they do not seek medical attention (Nishiura et al., 2020b). Estimates such as this therefore provide important insight by using a targeted population to assess the prevalence of asymptomatic viral shedding (Kupferschmidt and Cohen, 2020). It should be noted that the limited sensitivity of RT-PCR does not affect the estimate of the asymptomatic ratio, because the sensitivity is cancelled out from the right-hand side of the equation. However, a weakness of this study is that age-dependence and other aspects of heterogeneity were ignored, because the samples relied on Japanese evacuees from Wuhan. Despite the small sample size, this estimation indicates that perhaps less than a half of COVID-19-infected individuals are asymptomatic. This ratio is slightly smaller than that for influenza, which has been estimated at 56–80% (Hsieh et al., 2014) using similar definitions for symptomatic individuals. There is great need for further studies on the prevalence of asymptomatic COVID-19 infections to guide epidemic control efforts. Ethical approval Not required. Conflict of interest We declare that we have no conflict of interest.

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          Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

          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. 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. 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). 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.)
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            Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data

            The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.
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              The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020

              A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.
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                Author and article information

                Journal
                International Journal of Infectious Diseases
                International Journal of Infectious Diseases
                Elsevier BV
                12019712
                March 2020
                March 2020
                Article
                10.1016/j.ijid.2020.03.020
                e8fc8591-11ad-4862-8fc1-9b5578b1ea3b
                © 2020

                https://www.elsevier.com/tdm/userlicense/1.0/

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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