Systematic review and meta-analysis of the efficacy and safety of oseltamivir (Tamiflu) in the treatment of Coronavirus Disease 2019 (COVID-19)

Abstract

Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.

Fig 1. PRISMA flow diagram.

Figure shows the entire screening process.

Fig 2. Summary for the ROBINS-I tool.

Shows RoB assessment for primary outcome studies.

Fig 3. Forest plot.

Shows pooled analysis for COVID-19 patients’ survival in the oseltamivir (monotherapy or combination) groups versus other drugs (alone or in combination) treatment.

Fig 4. Forest plot.

Shows graphical presentation of the meta-analysis comparing the survival of the Oseltamivir group to the Arbidol group.

Fig 5. Forest plot.

Shows the meta-analysis comparing the survival of the oseltamivir group to the Immunoglobulins group.

Fig 6. Forest plot.

Shows the meta-analysis comparing the survival of the oseltamivir group to the type 1 Interferon/Infliximab groups.

Fig 7. Forest plot.

Shows the meta-analysis comparing the survival of the oseltamivir group to the Lopinavir/Ritonavir group.

Fig 8. Forest plot.

Shows the sensitivity analysis for COVID-19 patients’ survival in the oseltamivir (monotherapy or combination) groups versus other drugs (alone or in combination) treatment.

Fig 9. Forest plot.

Shows the pooled effect estimate of the duration of hospitalisation of oseltamivir alone/combination compared with other drugs alone/combination.

Fig 10. Forest plot.

Shows the sensitivity analysis pooled estimate of the duration of hospitalisation of oseltamivir alone/combination vs other drugs.

Fig 11. Forest plot.

Shows the effect estimate of duration of hospitalisation of oseltamivir monotherapy vs Corticosteroid monotherapy.

Fig 12. Forest plot.

Shows the pooled analysis of the duration of hospitalisation of oseltamivir monotherapy vs HCQ monotherapy.

Fig 13. Post-hoc analysis.

Shows the trial sequential analysis result comparing the survival of COVID-19 patients treated with oseltamivir versus other drugs.

Fig 14. Post-hoc analysis.

Shows the trial sequential analysis result comparing the survival of COVID-19 patients treated with oseltamivir versus other drugs after removing one study.

Fig 15. Post-hoc analysis.

Shows the trial sequential analysis result comparing the duration of hospitalisation of COVID-19 patients treated with oseltamivir versus other drugs.