**Background:** The COVID-19 pandemic had a global impact on physical, mental, and social health. Early data suggested a decline in step counts worldwide, but factors contributing to reduced activity had not been identified. This study aimed to examine whether COVID-19 was associated with daily activity among All of Us (AOU) research program participants, hypothesizing that a decline in activity across the US would persist after most social distancing recommendations were relaxed, and that socioeconomic factors and mental health status would continue to affect reduced activity.
**Methods:** Using the AOU Research Program Controlled Tier data set (released June 2022), this cohort study included participants who wore a Fitbit device tracking physical activity for at least 10 days each month. Daily steps (averaged monthly) were examined over 4 years from January 2018 through December 2021. Counterfactual analysis based on 2 years of activity data preceding COVID-19 was used to estimate post-pandemic steps. Differences in observed and estimated post-COVID-19 daily steps were examined using Wilcoxon rank sum test with continuity correction. Surveys assessed sociodemographic factors, mental health, location, and deprivation index at enrollment. Linear mixed models examined associations of COVID-19 vaccine, comorbidities, sociodemographic, and mental health factors with differences in observed and estimated post-COVID-19 daily steps. Analysis was conducted using R version 4.2.2 with a significance threshold of P < .05 in 2-sided tests.
**Key Results:** Data from 5443 participants (3903 [71.7%] female; 257 [4.7%] Black, 4681 [86.0%] White, 505 [9.3%] other; median [IQR] age, 53 [38-64] years) were analyzed. Median (IQR) observed daily step counts pre-COVID-19 and post-COVID-19 were 7808 (5923-10108) steps and 7089 (5101-9740) steps, respectively. The counterfactual model estimated participants walked 575 (95% CI, 521-629) fewer steps per day post-COVID-19 compared with observed daily steps (P < .001). The difference between observed and estimated post-COVID-19 steps was significantly explained by younger age (β = −243 per 10-year decrease; P < .001), Northeast region compared with other regions (Northeast vs others, β = −288, P < .001), and higher deprivation index (β = −477 per 0.1 increment; P < .001). Post-COVID-19 step counts were also explained by COVID-19 vaccination status (vaccinated vs unvaccinated: β = 48; P < .01), depression (β = −36 per 1 score increment; P < .01), and psychological stress (β = −13 per 1 score increment; P < .01). No association was found between reduced step counts and sex or comorbidities such as obesity, diabetes, coronary artery disease, hypertension, or cancer.
**Clinical Implications:** These findings suggest a consistent, widespread, and significant decline in activity following the onset of COVID-19 in the US. Vulnerable populations, including individuals at a lower socioeconomic status and those reporting worse mental health in the early COVID-19 period, were at the highest risk of reduced activity. The statistically significant decline in daily step counts persisted even after most COVID-19-related restrictions were relaxed, suggesting COVID-19 affected long-term behavioral choices. The study had limitations including selection bias (majority were White, young, and active), stringent criteria for valid tracking days potentially biasing results toward more active individuals, and likely underestimation of COVID-19 infection prevalence (only 2% documented). Despite these limitations, the study showed COVID-19 to be associated with decreased physical activity, which may have implications for future cardiometabolic risk with the potential to exacerbate health disparities related to socioeconomic status and mental health.