key: cord-0810805-jsppnw9d authors: Jia, Xiaoqian; Chen, Junxi; Li, Liangjing; Jia, Na; Jiangtulu, Bahabaike; Xue, Tao; Zhang, Le; Li, Zhiwen; Ye, Rongwei; Wang, Bin title: Modeling the Prevalence of Asymptomatic COVID-19 Infections in the Chinese Mainland date: 2020-08-04 journal: Innovation DOI: 10.1016/j.xinn.2020.100026 sha: 6f0193c1e29e481b0dcd473ffed7182b9de2613b doc_id: 810805 cord_uid: jsppnw9d Abstract Recently, considerable efforts have been focused on intensifying the screening process for asymptomatic COVID-19 cases in the Chinese Mainland, especially for up to 10 million citizens living in Wuhan City by nucleic acid testing. However, a high percentage of domestic asymptomatic cases did not develop into symptomatic ones, which is abnormal and has drawn considerable public attention. Here, we aimed to investigate the prevalence of COVID-19 infections in the Chinese Mainland from a statistical perspective, as it is of referential significance for other regions. By conservatively assuming a development time lag from pre-symptomatic (i.e. referring to the infected cases were screened prior to the COVID-19 symptom onset) to symptomatic as an incubation time of 5.2 days, our results indicated that 92.5% of those tested in Wuhan City, China and 95.1% of those tested in the Chinese Mainland should have COVID-19 syndrome onset, which was extremely higher than their corresponding practical percentages of 0.8% and 3.0%, respectively. We propose that a certain false positive rate may exist if large-scale nucleic acid screening tests for asymptomatic cases are conducted in common communities with a low incidence rate. Despite adopting relatively high-sensitivity, high-specificity detection kits, we estimated a very low prevalence of COVID-19 infections, ranging from 10−6 to 10−4 in both Wuhan City and the Chinese Mainland. Thus, the prevalence rate of asymptomatic infections in China had been at a very low level. Further, given the lower prevalence of the infection, close examination of the data for false positive results is necessary to minimize social and economic impacts. The sudden emergence and rapid global spread of the novel coronavirus SAR-CoV-2 has created a daunting public health challenge, resulting in ~2. 7 2020. This has caused increasing concern among researchers, as COVID-19 transmission appeared to be well under control since mid-March in the Chinese Mainland. China, the United States, Iceland, Korea, Japan, and others (e.g., the Diamond Princess cruise ship) ( Our study comprised the following three steps. First, the percentage of pre-symptomatic and subclinical infection of the officially reported COVID-19 cases were modeled using an assumed "development lag", which is the time interval from an asymptomatic COVID-19 confirmation (prior to syndrome onset) to the confirmation of a symptomatic case based on guidelines set by the NHC. The PPV was estimated approximately. Second, based on the sensitivity and specificity of commercially available RNA diagnostic kits, the prevalence of the COVID-19 infection was calculated using Bayes' formula. Third, we compared the up-to-date related prevention and control measures on asymptomatic infections among the typical countries. The referential significance of our study is proposed. In information, as summarized in Table 1 . Assuming that the biological samples of all participants were detected by an RNA kit with one test, without an immediate second confirmation before reporting to the NHC, we can estimate the detection specificity, as described in "Estimation of the In several previous studies, the percentage of asymptomatic cases that developed into symptomatic ones ranged from 70.8% to 100% (Table S4) reported data from the Wuhan population (see Table S2 ). However, even when the sensitivity and specificity of the test kit are very high, close to 100%, significantly overestimated asymptomatic infection rates will occur if the prevalence is very low, as mentioned in a previous study (Gao et al., 2020) . Considering the improvement in COVID-19 detection techniques in China at the time of this study, we assumed that the practical sensitivity and specificity should be higher. Due to the different stages of COVID-19 in various countries, the control and prevention measures for asymptomatic infections are highly dependent on location ( Africa, and Oceania, the median (IQR) COVID-19 prevalence was 6.0/10,000 (0.03/10,000-50.6/10,000) (Table S3) . If a false positive rate is a possibility, a confirmation test is immediately warranted in large-scale screening tests of affected communities. The key limitation of our study was that the main findings were inferred by a modeling simulation based on certain assumptions, especially, that a one-time test was used to screen for asymptomatic infections during a large-scale survey. Also, we did not have sufficient data on the sensitivity and specificity for some of the serum antibody tests administered to reported asymptomatic cases. In addition, the ethnicity and clinical diagnostics of the included population were not obtained, thus we cannot assert most of the screened asymptomatic cases definitely have a developing lag. Likewise, the reported number of asymptomatic cases may be derived based on different strategies, which were also not available. Overall, our study provides a snapshot for a given study period for policy reference, with two important advantages. Presymptomatic SARS-CoV-2 infections and transmission in a Skilled Nursing Facility Clinical characteristics of pregnant women infected with Coronavirus Disease 2019 in Wuhan The epidemiological characteristics of infection in close contacts of COVID-19 in Ningbo city Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village COVID-19 antibody seroprevalence in Advances on the asymptomatic infection Clinical characteristics of Coronavirus Disease 2019 in China Spread of SARS-CoV-2 in the Icelandic population Comparison and analysis of the detection performance of six new coronavirus nucleic acid detection reagents Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing Bayes' theorem applied to perimetric progression detection in glaucoma: from specificity to positive predictive value Epidemiologic characteristics of early cases with 2019 novel coronavirus (2019-nCoV) disease in Korea Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a Long-Term Care Skilled Nursing Facility -King County The incubation period of Coronavirus Disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and Application Study on the relationship between the predicted value of HIV antibody detection and the population infection rate Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections 2019-nCoV on-site rapid testing product development emergency project declaration guide National Health Commission of the People's Republic of China Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19) The rate of underascertainment of Novel Coronavirus (2019-nCoV) infection: estimation using Japanese passengers data on evacuation flights Singapore claims first use of antibody test to track coronavirus infections Comparison of diagnostic efficacy among three test kits for SARS-CoV-2 nucleic acid detection The State Council of the People's Republic of China (China S.C.). (2020a) Guidance group of the Central Committee to Hubei: It's urgent to collect all receivables The State Council of the People's Republic of China (China S.C.). (2020b). Management of asymptomatic infection with SARS CoV 2 The State Council of the People's Republic of China (China S.C.). (2020c) Notice on further strengthening responsibility implementation and improving prevention and control work Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in COVID-2019 Situation Reports