COVID-19 Evidence Alerts
from McMaster PLUS^TM

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs. Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low. Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Emergency Medicine rater

As with all systematic reviews, the results are limited by the quality of the studies included and the variability in measured outcomes between studies. This systematic review shows a benefit for corticosteroids in all cause mortality in patients with severe or critical Covid-19 infections. Mortality outcomes were not obvious for any other therapy. While adverse event profile of drugs such as remdesivir is favourable, it does not appear to influence all cause mortality outcomes. Hydroxychloroquine did not have any effect on mortality in any severity group for Covid-19 infections. Other antiviral and immunotherapy treatments did not confer any benefits on survival. The authors look upon this as a living study and results may change for various classes of drug as further studies are reported and added to the analysis.

Internal Medicine rater

This well-conducted network meta-analysis of Covid-19 treatments gives a rather balanced view of the pharmacotherapy available for this emerging condition. Still, the results meet conclusions already widely known in the medical community.

Respirology/Pulmonology rater

Lopinavir/ritonavir, plasma, hydroxychloroquine don’t work so this is really of limited relevance. Steroids were rightly highlighted. There is little mention of tocilizumab; although, trials were included. It does have clinical efficacy and now is in use of UK. Remdesivir data of some relevance as it seems to have efficacy in mild disease so cost benefits more finely balanced.