Estimation of R(t) based on illness onset data: An analysis of 1907-1908 smallpox epidemic in Tokyo.

R(t), the actual average number of secondary cases per primary case at calendar time t, is epidemiologically useful in assessing transmission dynamics in a population with varying susceptibility levels. However, a technical limitation of existing methods of estimating R(t) is the reliance on the daily number of cases with illness onset and the distribution of the serial interval, although the estimator of R(t) should be calculated as the ratio of newly infected cases at time t to the total number of potentially infectious people at the same time. Using historical data of a smallpox outbreak in Tokyo City, Japan, approximately 100 years ago, we propose a new method to compute R(t) that can be estimated using information on illness onset. Our method decomposes the mechanism of transmission into two distinct pieces of information: the frequency of secondary transmission relative to disease age and the probability density function of the incubation period. Employing a piecewise constant model, our maximum likelihood estimates of R(t) dropped below unity (0.6; 95% confidence interval: 0.5-0.7) for the period from Day 64 to Day 79, indicating that the epidemic was under control in this period. R(t) was continuously below one through the remaining days. The model prediction captured the overall observed pattern of the epidemic well. Our method is appropriate for acute infectious diseases other than smallpox for which variations in infectivity relative to disease age should be considered to correctly estimate the transmission potential, such as the ongoing global epidemic of coronavirus disease 2019 (COVID-19).

Exploring secondary SARS-CoV-2 transmission from asymptomatic cases using contact tracing data.

BACKGROUND: Individuals with asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can propagate the virus unknowingly and thus have been a focus of public health attentions since the early stages of the pandemic. Understanding viral transmissibility among asymptomatic individuals is critical for successful control of coronavirus disease 2019 (COVID-19). The present study aimed to understand SARS-CoV-2 transmissibility among young asymptomatic individuals and to assess whether symptomatology was associated with transmission of symptomatic vs. asymptomatic infections. METHODS: We analyzed one of the first-identified clusters of SARS-CoV-2 infections with multiple chains of transmission that occurred among university students in March 2020 in Kyoto prefecture, Japan, using discrete and two-type branching process models. Assuming that the number of secondary cases resulting from either primary symptomatic or asymptomatic cases independently followed negative binomial distributions, we estimated the relative reproduction numbers of an asymptomatic case compared with a symptomatic case. To explore the potential association between symptomatology and transmission of symptomatic vs. asymptomatic incident infections, we also estimated the proportion of secondary symptomatic cases produced by primary symptomatic and asymptomatic cases. RESULTS: The reproduction number for a symptomatic primary case was estimated at 1.14 (95% confidence interval [CI]: 0.61-2.09). The relative reproduction number for asymptomatic cases was estimated at 0.19 (95% CI: 0.03-0.66), indicating that asymptomatic primary cases did not result in sufficient numbers of secondary infections to maintain chains of transmission. There was no apparent tendency for symptomatic primary cases to preferentially produce symptomatic secondary cases. CONCLUSIONS: Using data from a transmission network during the early epidemic in Japan, we successfully estimated the relative transmissibility of asymptomatic cases of SARS-CoV-2 infection at 0.22. These results suggest that contract tracing focusing on symptomatic index cases may be justified given limited testing capacity.

Assessing Interventions against Coronavirus Disease 2019 (COVID-19) in Osaka, Japan: A Modeling Study.

Estimation of the effective reproduction number, R(t), of coronavirus disease (COVID-19) in real-time is a continuing challenge. R(t) reflects the epidemic dynamics based on readily available illness onset data, and is useful for the planning and implementation of public health and social measures. In the present study, we proposed a method for computing the R(t) of COVID-19, and applied this method to the epidemic in Osaka prefecture from February to September 2020. We estimated R(t) as a function of the time of infection using the date of illness onset. The epidemic in Osaka came under control around 2 April during the first wave, and 26 July during the second wave. R(t) did not decline drastically following any single intervention. However, when multiple interventions were combined, the relative reductions in R(t) during the first and second waves were 70% and 51%, respectively. Although the second wave was brought under control without declaring a state of emergency, our model comparison indicated that relying on a single intervention would not be sufficient to reduce R(t) < 1. The outcome of the COVID-19 pandemic continues to rely on political leadership to swiftly design and implement combined interventions capable of broadly and appropriately reducing contacts.

Transmissibility of asymptomatic COVID-19: Data from Japanese clusters.

BACKGROUND: The epidemiological importance of asymptomatic individuals who would never develop illness, compared to those who eventually develop symptoms, has yet to be fully clarified. METHODS: The very first cluster data in Tokyo and Kanagawa (n = 36) were analyzed. Movement of all close contact was restricted for 14 days and they underwent laboratory testing with polymerase chain reaction. The reproduction numbers of symptomatic and asymptomatic cases were estimated. RESULTS: The reproduction number for symptomatic cases was estimated to be 1.2 (95% confidence interval (CI): 0.5-2.9). The relative infectiousness of asymptomatically infected cases was estimated to be 0.27 (95% CI: 0.03-0.81) of symptomatic cases. CONCLUSION: The relative transmissibility of asymptomatic cases is limited. Observing clusters starting with symptomatic transmission might be sufficient for the control.