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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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          The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights

          From 29 to 31 January 2020, a total of 565 Japanese citizens were evacuated from Wuhan, China on three chartered flights. All passengers were screened upon arrival in Japan for symptoms consistent with novel coronavirus (2019-nCoV) infection and tested for presence of the virus. Assuming that the mean detection window of the virus can be informed by the mean serial interval (estimated at 7.5 days), the ascertainment rate of infection was estimated at 9.2% (95% confidence interval: 5.0, 20.0). This indicates that the incidence of infection in Wuhan can be estimated at 20,767 infected individuals, including those with asymptomatic and mildly symptomatic infections. The infection fatality risk (IFR)—the actual risk of death among all infected individuals—is therefore 0.3% to 0.6%, which may be comparable to Asian influenza pandemic of 1957–1958.
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            Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan

            Background Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms. Methods Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters <40, were collected from urban, rural areas and an isolated island in Taiwan during the 2005–2006 influenza season. Their hemagglutination inhibition antibody (HI Ab) serotiters against the 2005 A/New Caledonia/20/99 (H1N1) vaccine strain at pre-season and post-season were measured to determine the symptoms with the highest correlation with infection, as defined by 4-fold rise in HI titer. We estimate the asymptomatic ratio, or the proportion of asymptomatic infections, for schoolchildren during the 2005–6 influenza season when this vaccine strain was found to be antigenically related to the circulating H1N1 strain. Results Fever has the highest correlation with the 2005–06 seasonal influenza A(H1N1) infection, followed by headache, cough, vomiting, and sore throat. Asymptomatic ratio for the schoolchildren is found to range between 55.6% (95% CI: 44.7-66.4)-77.9% (68.8-87.0) using different sets of predictive symptoms. Moreover, the asymptomatic ratio was 66.9% (56.6-77.2) when using US-CDC criterion of fever + (cough/sore throat), and 73.0 (63.3-82.8) when under Taiwan CDC definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue). Conclusions Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates of symptomatic ratio of infected children has important clinical and public health implications.
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              ‘This beast is moving very fast.’ Will the new coronavirus be contained—or go pandemic?

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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
                7270890
                32179137
                © 2020

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

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

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