Efficacy of various treatment modalities for nCOV-2019: A systematic review and meta-analysis

Eur J Clin Invest. 2020 Nov;50(11):e13383. doi: 10.1111/eci.13383. Epub 2020 Sep 13.

Abstract

Background: Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients.

Methods: A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I2 < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.

Results: Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events.

Conclusion: Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.

Keywords: humans; interventions; nCOV-2019; novel coronavirus 2019; treatments.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adenosine Monophosphate / administration & dosage
  • Adenosine Monophosphate / analogs & derivatives
  • Alanine / administration & dosage
  • Alanine / analogs & derivatives
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antiviral Agents / therapeutic use*
  • COVID-19
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology*
  • Europe
  • Female
  • Humans
  • Lopinavir / administration & dosage
  • Male
  • Pandemics / prevention & control
  • Pandemics / statistics & numerical data
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology*
  • Prognosis
  • Ritonavir / administration & dosage
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Lopinavir
  • remdesivir
  • Adenosine Monophosphate
  • tocilizumab
  • Ritonavir
  • Alanine

Supplementary concepts

  • COVID-19 drug treatment