BACKGROUND: New York City and Long Island, NY were early foci of the COVID-19 epidemic in the US. The effects of COVID-19 on different sub-populations, and its key epidemiologic parameters remain unknown or highly uncertain. We investigated the epidemiology of COVID-19 from January to August of 2020 in an established academic monitoring cohort of N = 9,697 middle-aged World Trade Center responders residing in Long Island, NY. METHODS: A seroprevalence survey and a series of cross-sectional surveys were nested in a prospective cohort study. Measures included IgG antibody testing, SARS-CoV-2 polymerase chain reaction (PCR) testing, review of electronic medical records, and surveys of symptoms. Correlates of infection were analyzed with multivariable logistic regression. RESULTS: The cohort was predominantly men in their mid-fifties; 6,597 cohort members were successfully contacted (68%); 1,042 (11%) individuals participated in the seroprevalence survey; and 369 individuals (5.6% of 6,597 study participants) underwent PCR testing. The estimated standardized cumulative incidence was 21.9% (95%CI: 20.1-23.9%), the asymptomatic proportion was 16.4% (36/219; 95%CI: 11.8-22.0%), the case hospitalization ratio was 9.4% (36/385; 95%CI: 6.6-12.7%), the case fatality ratio was 1.8% (7/385; 95%CI: 0.7-3.7%), and the hospitalization fatality ratio was 8.3% (3/36; 95%CI: 1.8-22.5%). Confirmed SARS-CoV-2 infection was associated with younger age, race/ethnicity, and being currently employed. CONCLUSIONS: The results of the present study suggest a high cumulative incidence of SARS-CoV-2 among WTC responders in the spring and summer of 2020 and contribute to narrowing the plausible range of the proportion of infections that exhibit no symptoms. An increased risk of infection among younger employed individuals is likely to reflect a higher probability of exposure to the virus, and the racial disparities in the infection risk warrant further investigation.