Title:Combination Therapy with Favipiravir for Treatment of Hospitalized COVID-19 Adults
Volume: 2
Author(s): Maria-Fernanda Bonilla*, Martin E. Lascano, Rania El-Lababidi, Ahmad Nusair, Mohamad Mooty, Maher Balkis, Asim Malik, Terrence J. Lee-St. John and Madhu Sasidhar
Affiliation:
- Department of Infectious Diseases, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, P.O. Box 112412,United Arab Emirates
Keywords:
Favipiravir, COVID-19, SARS-CoV-2, Antivirals, RNA, Mortality.
Abstract: Background:
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.
Methods:
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.
Results:
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%).
Conclusion:
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.
