BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease due to 
SARS-COV-2. Patients with risk factors are vulnerable to severe morbidity and 
mortality. Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered 
possible COVID-19 treatments.
OBJECTIVE: To investigate the effectiveness and safety of FPV compared to HCQ in 
patients with COVID-19 as the standard of care approved by the national protocol 
there.
METHODS: This is a retrospective cohort study on patients with COVID-19 who were 
administered either FPV or HCQ at King Faisal Medical Complex, Taif, Saudi 
Arabia, from June 2020 to August 2020.
RESULTS: In total, 508 patients were included in the analysis. Patients were 
categorized into three groups by medication. Patients enrolled in this study 
were 244 (55.8%) on FPV, 193 (44.2%) on HCQ and 71 (13.81%) on neither 
medication. Patients who received FPV had higher age and greater comorbidity. 
Most of the patients were discharged on day 14 (n = 303, 59.6%), 26 (36.6%) in 
neither med, 154 (63.1%) in FPV and 123 (63.7%) in HCQ groups with significant 
difference between groups (P < 0.0001). Mortality rate was 8.2% (n = 20) in FPV 
and 7.3% (n = 14) in HCQ groups with significant difference between groups (P = 
0.048). Regarding drug safety, 19.7% of patients treated with FPV vs 7.8% HCQ 
have adverse effects with significant difference between groups (P < 0.0001). 
Most of the side effects were increase ALT and AST. Meanwhile, prolonged Q-T 
interval was reported only in the HCQ group (2.6%). From Cox regression 
modeling, only mechanical ventilation due to Covid 19 was predictive for 
mortality (HR: 16.598, 95% CI: 7.095-38.828, P < 0.0001). Meanwhile, there was 
no significant difference in the prediction of discharge of FPV (vs HCQ) (HR: 
0.933, 95% CI: 0.729-1.195, P = 0.5843), predictors of mortality were HCQ (vs 
FPV) (HR: 2.3, 95% CI: 0.994-5.487, P = 0.0518). Kaplan-Meier survival curves 
showed improved survival time and discharged time among patients in the HCQ 
versus FPV group with an insignificant difference between them (P = 0.85, P = 
0.06, respectively).
CONCLUSION: The present study concluded that FPV and HCQ showed comparable 
efficacy in decrease mortality and oxygen requirements. FPV likely has a more 
favorable safety profile regarding cardiac toxicity. A randomized clinical trial 
with large patient numbers is recommended to confirm the effectiveness of these 
drugs in COVID-19 patients.