Abstract: Open Forum Infectious Diseases Brief Report Prospective Cohort of Fluvoxamine for Early Treatment of Coronavirus Disease 19 David Seftel1,2 and David R. Boulware3, 1 Golden Gate Fields Medical Clinic, Berkeley, California, USA, 2Enable Biosciences Inc, South San Francisco, California, USA, 3University of Minnesota Medical School, Minneapolis, Minnesota, USA We read with interest Lenze et al’s [1] double-blind randomized clinical trial testing fluvoxamine for early treatment of coronavirus disease 2019 (COVID-19). In this 152 person outpatient trial, fluvoxamine decreased clinical progression, defined as hypoxia (<92% oxygen saturation) coupled with either shortness of breath or hospitalization, from 8% (6 of 72) with observation alone to 0% (0 of 80) with fluvoxamine at up to 300 mg daily (P = .009) [1]. Although fluvoxamine is a selective serotonin reuptake inhibitor, fluvoxamine also activates sigma-1 receptors present intracellularly in the endoplasmic reticulum, thereby decreasing cytokine production [2]. We wish to share our recent real-world experience using fluvoxamine inspired by this recent trial. METHODS In November–December 2020, a mass outbreak of COVID-19 occurred in an occupational setting with congregate living at a horse racing track in California. We instituted 3 successive Received 21 December 2020; editorial decision 26 January 2021; accepted 27 January 2021. Correspondence: David Seftel, MD, MBA, Medical Director/Primary Care Clinician, Golden Gate Fields Medical Clinic, 1100 Eastshore Highway, Berkeley, CA 94710 (dseftel@ enablebiosciences.com). Open Forum Infectious Diseases®2021 © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com DOI: 10.1093/ofid/ofab050 Patient Consent Statement Patients consented for their medical treatment. As a quality improvement initiative, we assessed 14-day outcomes, analyzing the existing collected, deidentified data (Institutional Review Board exempt by the University of Minnesota). RESULTS Of 113 SARS-COV-2 antigen positive persons, approximately half were asymptomatic when initially tested. The median age was 42 years (interquartile range, 33 to 56), and 75% were men; 84% were Latino, and 14% were white. In total, 65 persons opted for fluvoxamine, and 48 opted for observation alone with no therapy. Demographics were generally similar among those choosing fluvoxamine versus observation, with the exception that more nonwhite persons opted for fluvoxamine (Table 1). Fewer patients opting for fluvoxamine were asymptomatic (38%) at time of initial diagnostic testing than those opting for observation (58%). Overall, 30% had 1 or more chronic medical comorbidities. Those opting for fluvoxamine had slightly more frequent diabetes (17% vs 8%) and slightly less treated hypertension (17% vs 35%) than those receiving observation. The incidence of subsequent hospitalization was 0% (0 of 65) with fluvoxamine and 12.5% (6 of 48) with observation (P = .005). Two persons required intensive care unit..