The mathematical modeling of infectious diseases aims to evaluate the transmissibility of the on-going spread of disease and guide the government's control strategies and interventions. In this paper, we propose a novel transmissibility indicator, reproduction factor, which evaluates the number of secondary infections from a single nonisolated infectious individual. In contrast to classic reproduction numbers, the reproduction factor explicitly considers the fraction of susceptible individuals (who are not immune to disease naturally or through vaccination) and the nonisolated population to evaluate near real-time transmissibility. Thus, it can be an effective indicator when the spread of disease has progressed and control strategies have been implemented. Other merits of the proposed reproduction factor include data-driven inference based on a Markov chain, which enables the inference of latent information, such as the number of nondetected infectious individuals and the number of daily new infections. We performed an extensive simulation using the COVID-19 datasets of Germany, Italy, South Korea, and California (the U.S.) to verify our model. We further compared the results with other transmissibility measures, including reproduction numbers, and the results of state-of-the-art epidemic models. Through the results, we confirmed that the proposed reproduction factor and corresponding inference model explained the COVID-19 datasets.