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Abstract   Background  Seroprevalence studies are important tools to estimate the prevalence of prior or recent SARS-CoV-2 infections. This information is critical for identifying hotspots and high-risk groups and informing public health responses to the COVID-19 pandemic. We conducted a city-level seroprevalence study in Holyoke, Massachusetts to estimate the seroprevalence of SARS-CoV-2 antibodies and risk factors for seropositivity.    Methods  We invited inhabitants of 2,000 randomly sampled addresses to participate between November 5 and December 31, 2020. Participants completed questionnaires measuring sociodemographic and health characteristics, and COVID-19 exposure history, and provided dried blood spots for measurement of SARS-CoV-2 IgG and IgM antibodies. To calculate total and group seroprevalence estimates, inverse probability of response weights were constructed based on age, gender, race/ethnicity and census tract to ensure estimates represented the city’s population.    Results  We enrolled 280 households including 472 individuals. 328 underwent antibody testing. The citywide weighted seroprevalence of SARS-CoV-2 IgG or IgM was 13.9% (95%CI 7.8 - 21.8) compared to 9.8% based on publicly reported case counts. Seroprevalence was 16.8% (95%CI 5.7 – 28.0) among individuals identifying as Hispanic compared to 8.9% (95%CI 3.0 - 14.7) among those identifying as White. Seroprevalence was 20.7% (95%CI 2.2 – 39.2) for ages 0-19; 13.8% (95%CI 5.6 – 22) for ages 20 – 44; 9.6% (95%CI 0 – 20.5) for ages 45 – 59; 4.8% (95%CI 0 – 10.2) for ages 60 – 84; and 42.9% (95%CI 0 – 100) for ages >85.  Table 1. Seroprevalence by antibody positivity profileTable 2. Unweighted and weighted seroprevalence by sociodemographic characteristicsFigure 1. Seroprevalence by Medical, Symptom, Testing and Exposure History.Conclusion  The measured SARS-CoV-2 seroprevalence in Holyoke was only 13.9% during the second surge of SARS-CoV-2 in this region, far from accepted thresholds for “herd immunity” and highlighting the need for expanding vaccination. Individuals identifying as Hispanic were at high risk of prior infection. Subsequent community-level serosurveys are necessary to guide local responses to the SARS-CoV-2 pandemic.    Disclosures    All Authors : No reported disclosures

396. Disparities in SARS-CoV-2 Antibody Prevalence: Findings from a Citywide Serosurvey in Holyoke, Massachusetts, November 2020–January 2021