Mathematical and Statistical Analysis of Doubling Times to Investigate the Early Spread of Epidemics: Application to the COVID-19 Pandemic

Abstract

Simple mathematical tools are needed to quantify the threat posed by emerging and re-emerging infectious disease outbreaks using minimal data capturing the outbreak trajectory. Here we use mathematical analysis, simulation and COVID-19 epidemic data to demonstrate a novel approach to numerically and mathematically characterize the rate at which the doubling time of an epidemic is changing over time. For this purpose, we analyze the dynamics of epidemic doubling times during the initial epidemic stage, defined as the sequence of times at which the cumulative incidence doubles. We introduce new methodology to characterize epidemic threats by analyzing the evolution of epidemics as a function of (1) the number of times the epidemic doubles until the epidemic peak is reached and (2) the rate at which the doubling times increase. In our doubling-time approach, the most dangerous epidemic threats double in size many times and the doubling times change at a relatively low rate (e.g., doubling times remain nearly invariant) whereas the least transmissible threats double in size only a few times and the doubling times rapidly increases in the period of emergence. We derive analytical formulas and test and illustrate our methodology using synthetic and COVID-19 epidemic data. Our mathematical analysis demonstrates that the series of epidemic doubling times increase approximately according to an exponential function with a rate that quantifies the rate of change of the doubling times. Our analytic results are in excellent agreement with numerical results. Our methodology offers a simple and intuitive approach that relies on minimal outbreak trajectory data to characterize the threat posed by emerging and re-emerging infectious diseases.