Determining the Covertness of COVID-19 - Wuhan, China, 2020.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has been going on for over a year and has reemerged in several regions. Therefore, understanding the covertness of COVID-19 is critical to more precisely estimating the pandemic size, especially the population of hidden carriers (those with very mild or no symptoms). METHODS: A stochastic dynamic model was proposed to capture the transmission mechanism of COVID-19 and to depict the covertness of COVID-19. The proposed model captured unique features of COVID-19, changes in the diagnosis criteria, and escalating containment measures. RESULTS: The model estimated that, for the epidemic in Wuhan, 79.8% (76.7%-82.7%) of the spread was caused by hidden carriers. The overall lab-confirmation rate in Wuhan up until March 8, 2020 was 0.17 (0.15-0.19). The diagnostic rate among patients with significant symptoms went up to 0.82 on March 8, 2020 from 0.43 on January 1, 2020 with escalating containment measures and nationwide medical supports. The probability of resurgence could be as high as 0.72 if containment measures were lifted after zero new reported (lab-confirmed or clinically confirmed) cases in a consecutive period of 14 days. This probability went down to 0.18 and 0.01 for measures lifted after 30 and 60 days, respectively. DISCUSSION: Consistent with the cases detected in Wuhan in mid-May, 2020, this study suggests that much of the COVID-19 pandemic is underreported and highly covert, which suggests that strict measures must be enforced continuously to contain the spread of the pandemic.

Epidemiological Characteristics and Factors Associated with Critical Time Intervals of COVID-19 in Eighteen Provinces, China: A Retrospective Study.

BACKGROUND: As COVID-19 ravages continuously around the world, more information on the epidemiological characteristics and factors associated with time interval between critical events is needed to contain the pandemic and to assess the effectiveness of interventions. METHODS: Individual information on confirmed cases from January 21 to March 2 was collected from provincial or municipal health commissions. We identified the difference between imported and local cases in the epidemiological characteristics. Two models were established to estimate the factors associated with time interval from symptom onset to hospitalization (TOH) and length of hospital stay (LOS) respectively. RESULTS: Among 7,042 cases, 3392 (48.17%) were local cases and 3304 (46.92%) were imported cases. Since the first intervention was adopted in Hubei on January 23, the daily reported imported cases reached a peak on January 28 and gradually decreased since then. Imported cases were on average younger (41 vs. 48), and had more male (58.66% vs. 47.53%) compared to local cases. Furthermore, imported cases had more contacts with other confirmed cases (2.80 ± 2.33 vs. 2.17 ± 2.10), which were mainly within family members (2.26 ± 2.18 vs. 1.57 ± 2.06). The TOH and LOS were 2.67 ± 3.69 and 18.96 ± 7.63 days respectively, and a longer TOH was observed in elderly living in the provincial capital cities that were higher migration intensity with Hubei. CONCLUSIONS: Measures to restrict traffic can effectively reduce imported spread. However, household transmission is still not controlled, particularly for the infection of imported cases to elderly women. It is still essential to surveil and educate patients about the early admission or isolation.

Prediction of the COVID-19 outbreak in China based on a new stochastic dynamic model.

The current outbreak of coronavirus disease 2019 (COVID-19) has become a global crisis due to its quick and wide spread over the world. A good understanding of the dynamic of the disease would greatly enhance the control and prevention of COVID19. However, to the best of our knowledge, the unique features of the outbreak have limited the applications of all existing dynamic models. In this paper, a novel stochastic model was proposed aiming to account for the unique transmission dynamics of COVID-19 and capture the effects of intervention measures implemented in Mainland China. We found that: (1) instead of aberration, there was a remarkable amount of asymptomatic virus carriers, (2) a virus carrier with symptoms was approximately twice more likely to pass the disease to others than that of an asymptomatic virus carrier, (3) the transmission rate reduced significantly since the implementation of control measures in Mainland China, and (4) it was expected that the epidemic outbreak would be contained by early March in the selected provinces and cities in China.

Estimation of incubation period distribution of COVID-19 using disease onset forward time: A novel cross-sectional and forward follow-up study.

We have proposed a novel, accurate low-cost method to estimate the incubation-period distribution of COVID-19 by conducting a cross-sectional and forward follow-up study. We identified those presymptomatic individuals at their time of departure from Wuhan and followed them until the development of symptoms. The renewal process was adopted by considering the incubation period as a renewal and the duration between departure and symptoms onset as a forward time. Such a method enhances the accuracy of estimation by reducing recall bias and using the readily available data. The estimated median incubation period was 7.76 days [95% confidence interval (CI): 7.02 to 8.53], and the 90th percentile was 14.28 days (95% CI: 13.64 to 14.90). By including the possibility that a small portion of patients may contract the disease on their way out of Wuhan, the estimated probability that the incubation period is longer than 14 days was between 5 and 10%.

Estimation of incubation period and generation time based on observed length-biased epidemic cohort with censoring for COVID-19 outbreak in China.

The incubation period and generation time are key characteristics in the analysis of infectious diseases. The commonly used contact-tracing-based estimation of incubation distribution is highly influenced by the individuals' judgment on the possible date of exposure, and might lead to significant errors. On the other hand, interval censoring-based methods are able to utilize a much larger set of traveling data but may encounter biased sampling problems. The distribution of generation time is usually approximated by observed serial intervals. However, it may result in a biased estimation of generation time, especially when the disease is infectious during incubation. In this paper, the theory from renewal process is partially adopted by considering the incubation period as the interarrival time, and the duration between departure from Wuhan and onset of symptoms as the mixture of forward time and interarrival time with censored intervals. In addition, a consistent estimator for the distribution of generation time based on incubation period and serial interval is proposed for incubation-infectious diseases. A real case application to the current outbreak of COVID-19 is implemented. We find that the incubation period has a median of 8.50 days (95% confidence interval [CI] [7.22; 9.15]). The basic reproduction number in the early phase of COVID-19 outbreak based on the proposed generation time estimation is estimated to be 2.96 (95% CI [2.15; 3.86]).

Estimation of the time-varying reproduction number of COVID-19 outbreak in China.

BACKGROUND: The 2019 novel coronavirus (COVID-19) outbreak in Wuhan, China has attracted world-wide attention. As of March 31, 2020, a total of 82,631 cases of COVID-19 in China were confirmed by the National Health Commission (NHC) of China. METHODS: Three approaches, namely Poisson likelihood-based method (ML), exponential growth rate-based method (EGR) and stochastic Susceptible-Infected-Removed dynamic model-based method (SIR), were implemented to estimate the basic and controlled reproduction numbers. RESULTS: A total of 198 chains of transmission together with dates of symptoms onset and 139 dates of infections were identified among 14,829 confirmed cases outside Hubei Province as reported as of March 31, 2020. Based on this information, we found that the serial interval had an average of 4.60 days with a standard deviation of 5.55 days, the incubation period had an average of 8.00 days with a standard deviation of 4.75 days and the infectious period had an average of 13.96 days with a standard deviation of 5.20 days. The estimated controlled reproduction numbers, Rc, produced by all three methods in all analyzed regions of China are significantly smaller compared with the basic reproduction numbers R0. CONCLUSIONS: The controlled reproduction number in China is much lower than one in all regions of China by now. It fell below one within 30 days from the implementations of unprecedent containment measures, which indicates that the strong measures taken by China government was effective to contain the epidemic. Nonetheless, efforts are still needed in order to end the current epidemic as imported cases from overseas pose a high risk of a second outbreak.