PMID- 34012398 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210522 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Comparative Effectiveness of Pharmacological Interventions for Covid-19: A Systematic Review and Network Meta-Analysis. PG - 649472 LID - 10.3389/fphar.2021.649472 [doi] LID - 649472 AB - 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. CI - Copyright (c) 2021 De Crescenzo, Amato, Cruciani, Moynihan, D'Alo, Vecchi, Saulle, Mitrova, Di Franco, Addis and Davoli. FAU - De Crescenzo, Franco AU - De Crescenzo F AD - Department of Psychiatry, University of Oxford, Oxford, United Kingdom. AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. AD - Paediatric University Hospital-Department (DPUO), Bambino Gesu Children's Hospital, Rome, Italy. FAU - Amato, Laura AU - Amato L AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Cruciani, Fabio AU - Cruciani F AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Moynihan, Luke P AU - Moynihan LP AD - Department of Acute Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. FAU - D'Alo, Gian Loreto AU - D'Alo GL AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Vecchi, Simona AU - Vecchi S AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Saulle, Rosella AU - Saulle R AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Mitrova, Zuzana AU - Mitrova Z AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Di Franco, Valeria AU - Di Franco V AD - Department of Anaesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. FAU - Addis, Antonio AU - Addis A AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. FAU - Davoli, Marina AU - Davoli M AD - Department of Epidemiology of the Regional Health Service Lazio, Rome, Italy. LA - eng PT - Journal Article PT - Review DEP - 20210503 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8126885 OTO - NOTNLM OT - COVID-19 OT - adults (MeSH) OT - network meta analysis OT - pharmacologic (drug) therapy OT - systematic (literature) review COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/21 06:00 MHDA- 2021/05/21 06:01 PMCR- 2021/05/03 CRDT- 2021/05/20 06:40 PHST- 2021/01/04 00:00 [received] PHST- 2021/04/16 00:00 [accepted] PHST- 2021/05/20 06:40 [entrez] PHST- 2021/05/21 06:00 [pubmed] PHST- 2021/05/21 06:01 [medline] PHST- 2021/05/03 00:00 [pmc-release] AID - 649472 [pii] AID - 10.3389/fphar.2021.649472 [doi] PST - epublish SO - Front Pharmacol. 2021 May 3;12:649472. doi: 10.3389/fphar.2021.649472. eCollection 2021.