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Efficacy of pharmacological interventions in COVID-19: A network meta-analysis
Sandhiya Selvarajan1, Annuja Anandaradje1, Santhosh Shivabasappa1
1Department of Clinical Pharmacology, JIPMER, Puducherry, India.
Insights
Dexamethasone and remdesivir show promise in treating COVID-19. Dexamethasone reduces mortality and improves recovery, while remdesivir aids recovery and reduces adverse events, offering better outcomes than other treatments.
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Coronavirus disease 2019 (COVID-19) poses a significant global health threat.
- Numerous therapeutic interventions have been investigated for COVID-19 treatment.
- Comparative effectiveness data for these interventions remain crucial for clinical decision-making.
Purpose of the Study:
- To conduct a network meta-analysis comparing various COVID-19 interventions.
- To evaluate the impact of interventions on mortality, clinical recovery, time to improvement, and serious adverse events.
- To provide evidence-based comparisons for guiding COVID-19 treatment strategies.
Main Methods:
- Systematic literature search of online databases using relevant MeSH terms.
- Inclusion of randomized controlled trials (RCTs) evaluating specific COVID-19 drugs.
- Independent data extraction and quantitative analysis using network meta-analysis.
Main Results:
- Dexamethasone (10% mortality reduction, 6% recovery increase) and remdesivir (10% recovery increase, 4-day faster improvement, 27% fewer adverse events) demonstrated benefits over standard care.
- Remdesivir showed lower mortality risk than tocilizumab and improved recovery/time to improvement versus hydroxychloroquine and tocilizumab.
- Remdesivir followed by tocilizumab was associated with fewer serious adverse events in moderate to severe COVID-19.
Conclusions:
- Dexamethasone improves clinical recovery and reduces mortality in COVID-19 patients.
- Remdesivir is associated with lower mortality risk compared to tocilizumab and better clinical outcomes than hydroxychloroquine and tocilizumab.
- Combination therapy with remdesivir and tocilizumab may reduce serious adverse events in severe COVID-19.
Aims:
To perform network meta-analysis for a head-to-head comparison of various interventions used in coronavirus disease 2019 (COVID-19) on mortality, clinical recovery, time to clinical improvement and the occurrence of serious adverse events.
Methods:
Systematic search was performed using online databases with suitable MeSH terms including coronavirus, COVID-19, randomized controlled trial, hydroxychloroquine, lopinavir/ritonavir, tocilizumab, remdesivir, favipiravir, dexamethasone and interferon-β. Data were independently extracted by 2 study investigators and analysed.
Results:
Out of 1225 studies screened, 23 were included for qualitative and quantitative analysis. Among the drugs studied, dexamethasone reduces mortality by 10%, with a relative risk of 0.90 (95% confidence interval [0.82-0.97]) and increases clinical recovery by 6% (relative risk 1.06, 95% confidence interval [1.02-1.10]) compared to standard of care. Similarly, remdesivir administered for 10 days increased clinical recovery by 10%, reduced time to clinical improvement by 4 days and lowered the occurrence of serious adverse events by 27% as compared to standard of care.
Conclusion:
In comparison to standard of care, dexamethasone was found to increase clinical recovery and lower mortality; remdesivir was significantly associated with a lower risk of mortality as compared to tocilizumab and higher clinical recovery and shorter time to clinical improvement as compared to hydroxychloroquine and tocilizumab; remdesivir followed by tocilizumab were found to have lesser occurrence of serious adverse events in patients with moderate to severe COVID-19.
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