Using specimens collected from the CHASING COVID Cohort, we estimated the incidence of SARS-CoV-2 infection by January 2021. Among 3,422 participants who tested negative in May-September 2020 and retested during November 2020-January 2021, 161 (4.7%) tested positive for COVID-19. Males were more likely to test positive compared to females. The likelihood of getting infected is also higher among Hispanic and Black non-Hispanic participants compared to White non-Hispanic. Essential workers had higher incidence than non-essential workers. Incidence rates were higher among participants from the South compared to the Northeast U.S. Participants who reported social distancing with people they did not know and with people they knew were less likely to contract COVID-19. Various factors and poor reach of public health strategies continue to drive transmission of SARS-CoV-2 across the U.S. While continuing to increase vaccine coverage, it remains critical for public health agencies to simultaneously reduce risk factors and address structural factors that contribute to high incidence and persistent inequities.