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Purpose: To assess the association of neighborhood demographic and socioeconomic characteristics with COVID-19 incidence and mortality in New York City (NYC) over the first two waves of outbreak., Methods: This retrospective study used neighborhood-level data from 177 modified ZIP code tabulation areas in NYC between March 01, 2020 and April 30, 2021., Results: Neighborhoods that were most severely impacted in wave 1 were also more affected in wave 2. Neighborhoods with a higher percentage of seniors (≥75 years), males, Black and Hispanic population, and large-size households had higher incidence rates of COVID-19 in wave 1 but not in wave 2. Neighborhoods with higher percentage of Black and Hispanic population and lower insurance coverage had higher death rate per capita and case fatality ratio in wave 1, and neighborhoods with higher percentage of Black and Asian population had elevated case fatality ratio in wave 2. Median household income was negatively associated with incidence rate and death rate per capita but not associated with case fatality ratio in both waves. Neighborhoods with more seniors had higher death rate and case fatality ratio in both waves., Conclusions: Neighborhood disparities in COVID-19 incidence and mortality across NYC neighborhoods were dynamic during the first two waves of outbreak., (Copyright © 2022 Elsevier Inc. All rights reserved.)