Comprehensive evaluation of the efficacy and safety of LPV/r drugs in the treatment of SARS and MERS to provide potential treatment options for COVID-19

Wu, Liusheng; Zheng, Yuzhen; Liu, Jixian; Luo, Ruixing; Wu, Dingwang; Xu, Pengcheng; Wu, Da; Li, Xiaoqiang

Coronavirus disease 2019 (COVID-19) experienced an outbreak that expanded worldwide. Lopinavir/ritonavir (LPV/r), which is used effectively for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections, was applied for COVID-19 treatment given similarities in the molecular structures of these viruses. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of lopinavir/ritonavir antiviral treatment in patients with SARS, MERS, and COVID-19. After registration with INPLASY, a search was conducted in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Cochrane Library, WanFang Data, China Biomedical Literature Database (CBM) and other databases for all relevant literature on lopinavir/ritonavir treatment of SARS, MERS and COVID-19. The Cochrane Collaboration’s bias risk assessment tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the literature, and RevMan 5.3 software was used to evaluate the relevant outcome indicators of the efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19. A total of 18 eligible studies (including randomized controlled studies, cohort studies, and case-control studies) were retrieved and included with a total of 2273 patients. The lopinavir/ritonavir group exhibited an increased nucleic acid conversion rate (P=0.004), higher virus clearance rate (P<0.0001), lower mortality rate (P=0.002), and reduced incidence of acute respiratory distress syndrome (ARDS) (P=0.02) compared with the control group. No significant benefit in the improvement rate of chest CT (P=0.08) or incidence of adverse events (P=0.45) was noted. The lopinavir/ritonavir group had a lower incidence of acute respiratory distress syndrome (P=0.02). According to the clinical prognostic results, the incidence of adverse events between the two groups was not statistically significant (P<0.0001). The efficacy of lopinavir/ritonavir in the treatment of patients with SARS, MERS and COVID-19 was significantly better than that of the control. Furthermore, the incidence of adverse events did not significantly increase. Lopinavir/ritonavir is effective in the treatment of COVID-19, and this combination should be further assessed in RCT studies. In addition, when we analyzed the differences in age and sex, we found that the differences were statistically significant in the safety and effectiveness of lopinavir/ritonavir in patients with COVID-19, and both of these factors played a significant role in the trial.