COVID-19 Research Paper Volume 13, Issue 18 pp 21866—21902

Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients: an updated network meta-analysis of randomized placebo-controlled trials

Qinglin Cheng1,2, *, , Junfang Chen1, *, , Qingjun Jia1, *, , Zijian Fang1, *, , Gang Zhao1, ,

  • 1 Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, China
  • 2 School of Medicine, Hangzhou Normal University, Hangzhou 310021, China
* Equal contribution

Received: May 5, 2021       Accepted: August 31, 2021       Published: September 16, 2021
How to Cite

Copyright: © 2021 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs).

Methods: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates.

Results: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96–393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21–30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15–18.30), ivermectin (OR 6.33, 95% CI 1.22–32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12–24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43–17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09–0.19), imatinib (OR 0.49, 95% CI 0.25–0.96), and baricitinib (OR 0.58, 95% CI 0.42–0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08–0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13–0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients.

Conclusion: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.


COVID-19: coronavirus disease 2019; LPV/r: lopinavir–ritonavir; CP: convalescent plasma; NMA: network meta-analysis; RPCTs: randomized placebo-controlled trials; ACM: all-cause mortality; VC: virological cure; TEAEs: treatment-emergent adverse events; OR: odds ratio; CI: confidence interval; SOC: standard of care; SUCRA: surface under the cumulative ranking area; MS: multicenter study; DS: duration of study; DB: double blind; CD: crossover design; SS: sample size; IS: industry sponsorship; ID: inequalities in doses; RRB: risk of reported bias; IQR: interquartile range; ALA: α-Lipoic acid; HCQ: hydroxychloroquine; PL: peginterferon lambda; AZM: azithromycin; IDE: ivermectin/doxycycline; HDVD: high-dose vitamin D; HDIVZn: high-dose intravenous zinc; IFN-β: interferon beta; HCP: high dosage CT-P59; LCP: low dosage CT-P59; CPC: CT-P59 combined; LDB: low dosage bamlanivimab; MDB: moderate dosage bamlanivimab; HDB: high dosage bamlanivimab; LS: low dosage sarilumab; HS: high dosage sarilumab; NPF: novel probiotic formulation; IG: immunoglobulin gamma; LDI: low dosage ivermectin.