COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Huang YQ, Tang SQ, Xu XL, et al. No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study. Front Pharmacol. 2020 Jul 14;11:1071. doi: 10.3389/fphar.2020.01071. eCollection 2020.

Background: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, causing an unprecedented pandemic. However, there is no specific antiviral therapy for coronavirus disease 2019 (COVID-19). We conducted a clinical trial to compare the effectiveness of three antiviral treatment regimens in patients with mild to moderate COVID-19.

Methods: This was a single-center, randomized, open-labeled, prospective clinical trial. Eligible patients with mild to moderate COVID-19 were randomized into three groups: ribavirin (RBV) plus interferon-a (IFN-a), lopinavir/ritonavir (LPV/r) plus IFN-a, and RBV plus LPV/r plus IFN-a at a 1:1:1 ratio. Each patient was invited to participate in a 28-d follow-up after initiation of an antiviral regimen. The outcomes include the difference in median interval to SARS-CoV-2 nucleic acid negativity, the proportion of patients with SARS-CoV-2 nucleic acid negativity at day 14, the mortality at day 28, the proportion of patients re-classified as severe cases, and adverse events during the study period.

Results: In total, we enrolled 101 patients in this study. Baseline clinical and laboratory characteristics of patients were comparable among the three groups. In the analysis of intention-to-treat data, the median interval from baseline to SARS-CoV-2 nucleic acid negativity was 12 d in the LPV/r+IFN-a-treated group, as compared with 13 and 15 d in the RBV+IFN-a-treated group and in the RBV+LPV/r+ IFN-a-treated group, respectively (p=0.23). The proportion of patients with SARS-CoV-2 nucleic acid negativity in the LPV/r+IFN-a-treated group (61.1%) was higher than the RBV+ IFN-a-treated group (51.5%) and the RBV+LPV/r+IFN-a-treated group (46.9%) at day 14; however, the difference between these groups was calculated to be statistically insignificant. The RBV+LPV/r+IFN-a-treated group developed a significantly higher incidence of gastrointestinal adverse events than the LPV/r+ IFN-a-treated group and the RBV+ IFN-a-treated group.

Conclusions: Our results indicate that there are no significant differences among the three regimens in terms of antiviral effectiveness in patients with mild to moderate COVID-19. Furthermore, the combination of RBV and LPV/r is associated with a significant increase in gastrointestinal adverse events, suggesting that RBV and LPV/r should not be co-administered to COVID-19 patients simultaneously.

Clinical Trial Registration:, ID: ChiCTR2000029387. Registered on January 28, 2019.

Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Internal Medicine rater

For the generalist, this information is important in terms of patient communication. Basically we do not know if any of the antiviral regimes have an effect. All we know is that the different regimes are equivalent to each other.