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This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval 470 ms in men or 480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin