Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.