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Background, Objective: We studied the effectiveness and safety of Hydroxychloroquine (HCQ) preexposure prophylaxis against COVID-19 in Healthcare workers (HCWs) previous studies being inconclusive due to small sample and lack of risk stratification Design and setting: Prospective, observational, multicenter cohort study in 44 hospitals in 17 Indian states during May-Sept 2020 Participants: 12089 Consenting Doctors, nurses, ancillary staff likely exposed to COVID-19 patients irrespective of whether taking HCQ preexposure prophylaxis (4257) or not (7826) participated,(in 6 data missing) Measurements: Data was collected on a self administered online questionnaire. Statistical analysis was done on SPSS version 20.

Results

Age above 45 years, diabetes, hypertension, history of COVID contact were independent risk factors for COVID positivity. HCQ intake did not show an independent association. However, when adjusted for other risk factors, HCQ dose as per Government recommendations, 2-3, 4-5 and 6 or more weeks reduced the probability of COVID positivity by 34%, 48%, 72% respectively. COVID free median survival time was higher in non-diabetics, non-hypertensives, persons below 45 years, with no prior exposure to COVID case and those who took HCQ for more than 6 weeks With modeling extent of risk reduction under different scenarios of risk and HCQ intake was 1-65%. Major adverse events reported were GI disorder, palpitation, giddiness and 140 persons discontinued due to adverse events.