Combination Therapy with Favipiravir for Treatment of Hospitalized COVID-19 AdultsAlternate Title: Combination Therapy with Favipiravir for Treatment
Maria-Fernanda Bonilla1, *, Martin E. Lascano2, Rania El-Lababidi3, Ahmad Nusair1, Mohamad Mooty1, Maher Balkis1, Asim Malik1, Terrence J. Lee-St. John4, Madhu Sasidhar5
1 Department of Infectious Diseases, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412, United Arab Emirates
2 Department of Nephrology, Medical Subspecialties Institute, and Division of Medical Informatics, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412, United Arab Emirates
3 Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412, United Arab Emirates
4 Department of Academics, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412, United Arab Emirates
5 Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412, United Arab Emirates
The optimal treatment for coronavirus disease 2019 (COVID-19) remains unclear. Favipiravir, an RNA polymerase inhibitor, has been used for COVID-19 but its clinical role and safety have not been established.
We evaluated the outcomes of hospitalized adults with COVID-19 on favipiravir as part of combination therapy between March 1 and June 1, 2020. Favipiravir was given at a loading dose of 1600 mg orally every 12 hours for 2 doses, followed by a maintenance dose of 600 mg orally every eight hours. We performed a retrospective assessment of virologic clearance, improvement in oxygenation, clinical improvement and possible adverse effects.
One hundred and nine patients received favipiravir for a mean duration of 5.32 days. Mean time from symptom onset to initiation of favipiravir (day 0) was 4.89 days. Quick Sequential Organ Failure Assessment score was <2 in 83 patients (76.1%), and 17 patients (15.6%) were on invasive mechanical ventilation at day 0. All patients received at least one additional antiviral, 50 patients (45.9%) received tocilizumab and 14 patients (12.8%) received convalescent plasma. Mean clinical and oxygenation improvement at day 28 were 79.8% and 81.6%, respectively, including 10/17 patients (58.8%) who were extubated. There was no statistically significant difference in mean viral RNA clearance time between patients that received >7 days and those receiving <7 days of favipiravir. Mortality was 9.2%. Main adverse events leading to early favipiravir discontinuation were QTc interval prolongation (11%) and hypertriglyceridemia (8.3%).
Early use of favipiravir as part of combination therapy was associated with improved outcomes, a low mortality rate and a high rate of clinical and oxygenation improvement in patients with mild, moderate, and severe COVID-19. There was no impact on virologic clearance. No severe adverse effects were recorded. The effect of favipiravir as monotherapy and as part of early combination therapy need to be elucidated further in randomized clinical trials.
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
* Address correspondence to this author at Department of Infectious Diseases, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412, United Arab Emirates; Tel: +971-2-501-9000, Ext. 41038; E-mail: BonillM@ClevelandClinicAbuDhabi.ae
Abdullah Shehab Emirates Cardiac Society Emirates Medical Association Dubai (UAE) Biography
Biography of Abdullah Shehab
Dr. Abdullah Shehab has 22 years of experience in Internal medicine, cardiology and interventional cardiology and medical education. Currently, he serves as the General Secretary of Emirates Cardiac Society and Vice President of Gulf Intervention Society. He is a Fellow of royal college of physicians UK, American college of physician, European society of cardiology, of American college of cardiology, American society of cardiac intervention and fellow of American heart association. Professor Shehab is the Chief editor of Emirates Medical Journal and also serves as editor in many other regional and international journals. Dr. Shehab has published 149 paper in Medline. His research interest includes: Heart failure, Coronary artery disease, Dyslipidaemia, Hypertension, Arrhythmias, Cardiac intervention, Cardiac imaging, Screening for cardiac disease in sport players, Cardiovascular disease in pregnancy.