Differences between the true reproduction number and the apparent reproduction number of an epidemic time series

Abstract

The time-varying reproduction number $R\left(t\right)$ measures the number of new infections per infectious individual and is closely correlated with the time series of infection incidence by definition. The timings of actual infections are rarely known, and analysis of epidemics usually relies on time series data for other outcomes such as symptom onset. A common implicit assumption, when estimating $R\left(t\right)$ from an epidemic time series, is that $R\left(t\right)$ has the same relationship with these downstream outcomes as it does with the time series of incidence. However, this assumption is unlikely to be valid given that most epidemic time series are not perfect proxies of incidence. Rather they represent convolutions of incidence with uncertain delay distributions. Here we define the apparent time-varying reproduction number, $R_A\left(t\right)$, the reproduction number calculated from a downstream epidemic time series and demonstrate how differences between $R_A\left(t\right)$ and $R\left(t\right)$ depend on the convolution function. The mean of the convolution function sets a time offset between the two signals, whilst the variance of the convolution function introduces a relative distortion between them. We present the convolution functions of epidemic time series that were available during the SARS-CoV-2 pandemic. Infection prevalence, measured by random sampling studies, presents fewer biases than other epidemic time series. Here we show that additionally the mean and variance of its convolution function were similar to that obtained from traditional surveillance based on mass-testing and could be reduced using more frequent testing, or by using stricter thresholds for positivity. Infection prevalence studies continue to be a versatile tool for tracking the temporal trends of $R\left(t\right)$, and with additional refinements to their study protocol, will be of even greater utility during any future epidemics or pandemics.