Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.01.16.21249941; this version posted January 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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 4.0 International license . Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19? Seyed Parsa Eftekhar1, Sohrab Kazemi2, Mohammad Barary1, Mostafa Javanian3, Soheil Ebrahimpour3, Naghmeh Ziaei4 * 1- Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran. 2- Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical Sciences, Babol, Iran. 3- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, I.R. Iran. 4- Department of Cardiology, Babol University of Medical Sciences, Babol, Iran. *Corresponding Author: Naghmeh Ziaei, Department of Cardiology, Babol University of Medical Sciences, Babol, Iran, Tel: +989111131748, Email: (ziaiexn@yahoo.com). Abstract Background: Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause Torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods: This was a retrospective cohort study. 172 patients with COVID-19 included, hospitalized at hospitals of Babol University of Medical Sciences between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results: 83.1% of patients received hydroxychloroquine plus azithromycin vs 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4. The mean of post-treatment QTc interval in the monotherapy group was shorter than the mean of post-treatment QTc interval in the combination therapy group but it had no significant statistical difference (462.5 ± 43.1 milliseconds vs 464.3 ± 59.1 milliseconds; P = 0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, 14 patients did not continue therapy after 4 days. Conclusion: Hospitalized patients treated with hydroxychloroquine with or without azithromycin, had no significant NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. difference in prolongation of QT interval and outcome. But the number of patients with prolonged QT intervals in this study emphasizes careful cardiac monitoring during therapy; especially in high-risk patients. Keywords: Hydroxychloroquine, Azithromycin, QTc interval, Torsade de pointes, COVID-19, novel coronavirus