Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.07.01.22277058; this version posted July 3, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 Title: Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among 2 health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial 3 Running Title: Hydroxychloroquine pre-exposure prophylaxis for SARS-CoV-2 4 5 Authors: Vanessa N. Raabe, MD1; Andrew Fleming, MD1,2; Marie I. Samanovic, Ph. D1; Lilin 6 Lai, MD1,3; Hayley M. Belli, Ph. D4; Mark J. Mulligan, MD1; H. Michael Belmont, MD5 7 8 Affiliations: 9 1 Division of Infectious Diseases & Immunology and NYU Langone Vaccine Center, Department 10 of Medicine, New York University Grossman School of Medicine 11 2 12 New York University Long Island School of Medicine 13 3 Current affiliation: Emory Vaccine Center, Emory University School of Medicine 14 4 Division of Biostatistics, Department of Population Health, New York University Grossman 15 School of Medicine 16 5 17 School of Medicine Current affiliation: Division of Infectious Diseases & Immunology, Department of Medicine, Department of Rheumatology, Department of Medicine, New York University Grossman 18 19 Corresponding Author: Vanessa Raabe, 430 E 29th St., Alexandria Center for Life Sciences West 20 Tower, 3rd Floor, New York, NY 10016. Vanessa.Raabe@nyulangone.org 21 22 World Count: Abstract – 274; Text - 3041 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.07.01.22277058; this version posted July 3, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 23 Abstract: 24 Background: Aerosol-generating procedures increase the risk of severe acute respiratory 25 syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs). An 26 effective pre-exposure prophylaxis would mitigate this risk. 27 28 Objective: To determine the efficacy of pre-exposure prophylactic hydroxychloroquine for the 29 prevention of SARS-CoV-2 infection and symptomatic coronavirus 19 disease (COVID-19) 30 among HCWs at high occupational risk of SARS-CoV-2 exposure. 31 32 Methods: 130 HCWs in the New York University Langone Health System (NYULHS) who 33 performed aerosol-generating procedures on patients with COVID-19 or provided bedside care 34 for inpatients with COVID-19 or persons with suspected COVID-19 in an emergency 35 department, for at least three shifts in a 7-day period, during the first 2020 COVID-19 wave in 36 New York City were enrolled. Participants elected to take oral hydroxychloroquine, 600 mg on 37 day 1 followed by 200 mg daily, or not take hydroxychloroquine for up to 90 days. Participants 38 self-collected dried blood spots and completed digital questionnaires regarding COVID-19 39 symptoms, adverse events, and other COVID-19 medication use. 40 41 Results: Six participants (7.5%) seroconverted during the trial: four who took 42 hydroxychloroquine..