The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients

Abstract

Enzyme inhibitors are frequently used to treat viral illnesses. Protease inhibitors are a promising class for combating novel and life-threatening viral infections. This research aimed to evaluate the efficacy and safety of lopinavir/ritonavir monotherapy or lopinavir/ritonavir plus interferon for the treatment of COVID-19. The PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for English articles with full texts available online. ReviewManager software was used to conduct a meta-analysis, subgroup analysis, and sensitivity analysis. Following the creation of the protocol, the collected sources were sorted into categories and evaluated for quality. Risk and hazard ratios and the random effects model were implemented, with statistical heterogeneity assigned using the Higgins I2 statistic. Lopinavir/ritonavir, with or without interferon, was associated with a nonsignificant higher mortality rate (odds ratio [OR] 1.29; 95% confidence interval [CI] 0.95 to 1.761; p = 0.1), as was clinical improvement (OR 1.2; 95% CI 0.8 to 1.84; p = 0.36). The difference in the length of hospital stay was in favor of the control group but statistically insignificant (standardized mean difference [SMD] 0.07; 95% CI −0.44 to 0.57; p = 0.79). The pooled data showed that lopinavir/ritonavir, with or without interferon, was associated with a significantly higher number of adverse events than placebo (OR 1.2; 95% CI 1.09 to 2.34; p = 0.02). Serious adverse events were insignificantly increased in the treated group over the control group (OR 1.2; 95% CI 0.96 to 2.12; p = 0.08). In the subgroup analysis, it was found that interferon used with lopinavir/ritonavir did not have a statistically significant effect on mortality rates (OR 1.75; 95% CI 0.87 to 3.55; p = 0.37), adverse effects (OR 1.20; 95% CI 0.75 to 1.91; p = 0.27), or serious adverse effects (OR 1.86; 95% CI 1.17 to 2.96; p = 0.33). Treatment with lopinavir/ritonavir alone or in combination with interferon for COVID-19 did not significantly outperform placebo in this study. Large randomized clinical trials are required to evaluate lopinavir/ritonavir in conjunction with interferon for the treatment of COVID-19. Such studies would benefit greatly from being conducted in a double-blind fashion at multiple locations.