BackgroundPopulation mobility is closely associated with coronavirus 2019 (COVID-19) transmission, and it could be used as a proximal indicator to predict future outbreaks, which could inform proactive non-pharmaceutical interventions for disease control. South Carolina (SC) is one of the states which reopened early and then suffered from a sharp increase of COVID-19.ObjectiveTo examine the spatial-temporal relationship between population mobility and COVID-19 outbreaks and use population mobility to predict daily new cases at both state- and county- levels in SC.MethodsThis longitudinal study used disease surveillance data and Twitter-based population mobility data from March 6 to November 11, 2020 in SC and its top five counties with the largest number of cumulative confirmed cases. Daily new case was calculated by subtracting the cumulative confirmed cases of previous day from the total cases. Population mobility was assessed using the number of users with travel distance larger than 0.5 mile which was calculated based on their geotagged twitters. Poisson count time series model was employed to carry out the research goals.ResultsPopulation mobility was positively associated with state-level daily COVID-19 incidence and those of the top five counties (i.e., Charleston, Greenville, Horry, Spartanburg, Richland). At the state-level, final model with time window within the last 7-day had the smallest prediction error, and the prediction accuracy was as high as 98.7%, 90.9%, and 81.6% for the next 3-, 7-, 14- days, respectively. Among Charleston, Greenville, Horry, Spartanburg, and Richland counties, the best predictive models were established based on their observations in the last 9-, 14-, 28-, 20-, and 9- days, respectively. The 14-day prediction accuracy ranged from 60.3% to 74.5%.ConclusionsPopulation mobility was positively associated with COVID-19 incidences at both state- and county- levels in SC. Using Twitter-based mobility data could provide acceptable prediction for COVID-19 daily new cases. Population mobility measured via social media platform could inform proactive measures and resource relocations to curb disease outbreaks and their negative influences.