Various Combination of Antiviral Treatment of COVID-19 Pneumonia; A Preliminary Observational Study

Background: Coronavirus disease 2019 (COVID-19) has emerged serious medical crisis worldwide. No regimen has been approved as gold standard of treatment. There were no report of other combinations of antiviral cocktail therapy. Methods: We compared time to recovery of  COVID-19 pneumonia patients who were treated with various combinations of lopinavir/ritonavir, darunavir /ritonavir, favipiravir, hydroxychloroquine, or no antiviral treatment with lopinavir/ritonavir plus high-dose oseltamivir. Results: Lopinavir/ritonavir plus high-dose oseltamivir had the best efficacy in terms of time to recovery compared to no antiviral treatment (P=0.003) and darunavir/ritonavir plus hydroxychloroquine and favipiravir (P =0.02). Lopinavir/ritonavir plus favipiravir had the borderline efficacy in terms of time to recovery compared to no antiviral treatment (P=0.05).There was no superior efficacy in terms of time to recovery of the combinations of darunavir/ritonavir plus hydroxychloroquine with or without favipiravir compared with no antiviral treatment (P>0.05). Darunavir/ritonavir plus hydroxychloroquine with or without favipiravir had similar efficacy to Lopinavir/ritonavir plus favipiravir (P>0.05). The patients who were treated with hydroxychloroquine 400-1200 mg/day had a significantly increased risk of death (P=0.04). Conclusions: The combination of lopinavir/ritonavir plus high-dose oseltamivir exhibited a trend of superiority compared to the combination of darunavir/ritonavir plus hydroxychloroquine and favipiravir and no antiviral treatment. However, the efficacy of the combinations of antiviral cocktail treatment of COVID-19 pneumonia should be further investigated in a randomized control study registerd as NCT04303299. Trial Registration: NCT04303299. Funding Statement: No support from any organization for the submitted work. Declaration of Interests: No conflicts of interest. Ethics Approval Statement: The electronic case report form and results of this study was acknowledge and approved by the independent ethics committee of the Ministry of Public Health for the NCT04303299 study, which we plan to start in the next phase as an open-label randomized controlled trial.