Estimating the Instantaneous Reproduction Number With Imperfect Data: A Method to Account for Case-Reporting Variation and Serial Interval Uncertainty

During an infectious disease outbreak, public health decision-makers require real-time monitoring of disease transmission to respond quickly and intelligently. In these settings, a key measure of transmission is the instantaneous time-varying reproduction number, Rt. Estimation of this number using a Time-Since-Infection model relies on case-notification data and the distribution of the serial interval on the target population. However, in practice, case-notification data may contain measurement error due to variation in case reporting while available serial interval estimates may come from studies on non-representative populations. We propose a new data-driven method that accounts for particular forms of case-reporting measurement error and can incorporate multiple partially representative serial interval estimates into the transmission estimation process. In addition, we provide practical tools for automatically identifying measurement error patterns and determining when measurement error may not be adequately accounted for. We illustrate the potential bias undertaken by methods that ignore these practical concerns through a variety of simulated outbreaks. We then demonstrate the use of our method on data from the COVID-19 pandemic to estimate transmission and explore the relationships between social distancing, temperature, and transmission.