Antiviral Treatment in COVID-19 Outpatients: A Systematic Review of Randomized Controlled Trials

Background: Most COVID-19 patients have mild or moderate illnesses that can progress to severe illness, leading to hospitalization and/or mortality. The use of antivirals to prevent the progression of COVID-19 in non-hospitalized patients shows conflicting result and efficacy remain unclear. This study evaluates the efficacy and safety of antivirals therapy in COVID-19 outpatients. Methods: Search were conducted in Pubmed, ScienceDirect, Cochrane Library, Springer, medRxiv, Journal Storage [JSTOR], and Directory of Open Access Journals [DOAJ] for articles investigating antivirals in COVID-19 outpatients. In addition, clinical and virological outcomes, COVID-19 hospitalization, all caused mortality, and adverse events were assessed. Results: Thirteen studies were included in this review. The consecutive data from these studies suggested that favipiravir is more optimally used in early disease, but improvement in symptoms shows inconsistent results. Meanwhile, molnupiravir shows consistent results, which can reduce hospitalization and mortality risk. In addition, remdesivir and nirmatrelvir-ritonavir have the potential to prevent the progression of COVID-19 in outpatients, but the data provided in this study are very limited. Finally, there is no significant difference in serious and non-serious adverse events, highlighting that antivirals have a good safety profile. Conclusion: This study provides an overview of the role of various antivirals therapy in COVID-19 outpatients. Molnupiravir, remdesivir, and nirmatrelvir-ritonavir have shown potential to prevent the progression of COVID-19 in early disease. However, this review was based on very limited data. Therefore, further clinical trials are needed to confirm this finding.