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Background  The spread of COVID-19 has highlighted the long-standing health inequalities across the U.S. as neighborhoods with fewer resources were associated with higher rates of COVID-19 transmission. Although the stay-at-home order was one of the most effective methods to contain its spread, residents in lower-income neighborhoods faced barriers to practicing social distancing. We aimed to quantify the differential impact of stay-at-home policy on COVID-19 transmission and residents’ mobility across neighborhoods of different levels of socioeconomic disadvantage.    Methods  This was a comparative interrupted time-series analysis at the county level. We included 2087 counties from 38 states which both implemented and lifted the state-wide stay-at-home order. Every county was assigned to one of four equally-sized groups based on its levels of disadvantage, represented by the Area Deprivation Index. Prevalence of COVID-19 was calculated by dividing the daily number of cumulative confirmed COVID-19 cases by the number of residents from the 2010 Census. We used the Social Distancing Index (SDI), derived from the COVID-19 Impact Analysis Platform, to measure the mobility. For the evaluation of implementation, the observation started from Mar 1st 2020 to 1 day before lifting; and, for lifting, it ranged from 1 day after implementation to Jul 5th 2020. We calculated a comparative change of daily trends in COVID-19 prevalence and Social Distancing Index between counties with three highest disadvantage levels and those with the least level before and after the implementation and lifting of the stay-at-home order, separately.    Results  On both stay-at-home implementation and lifting dates, COVID-19 prevalence was much higher among counties with the highest or lowest disadvantage level, while mobility decreased as the disadvantage level increased. Mobility of the most disadvantaged counties was least impacted by stay-at-home implementation and relaxation compared to counties with the most resources; however, disadvantaged counties experienced the largest relative increase in COVID-19 infection after both stay-at-home implementation and relaxation.    Conclusions  Neighborhoods with varying levels of socioeconomic disadvantage reacted differently to the implementation and relaxation of COVID-19 mitigation policies. Policymakers should consider investing more resources in disadvantaged counties as the pandemic may not stop until most neighborhoods have it under control.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12889-021-11149-1.

Differential impact of mitigation policies and socioeconomic status on COVID-19 prevalence and social distancing in the United States