Remdesivir for treatment of COVID-19; an updated systematic review and meta-analysis

Rezagholizadeh, Afra; Khiali, Sajad; Sarbakhsh, Parvin; Entezari‐Maleki, Taher

doi:10.1016/j.ejphar.2021.173926

Cited by 95 publications

(96 citation statements)

References 49 publications

(63 reference statements)

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“…Another network meta-analysis of four RCTs by Yokoyama et al [ 24 ] demonstrated a higher clinical improvement rate in both 5-day (OR 1.89; 95% CI 1.40–2.56) and 10-day (OR 1.38; 95% CI 1.15–1.66) remdesivir groups compared to a standard care group. A recent systematic reviews and meta-analysis of RCTs [ 17 , 20 , 26 ] reported a consistent clinical benefit of remdesivir in comparison to a placebo or standard care.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of four studies [ 34 ] revealed that remdesivir-treated patients had a lower risk of mortality than placebo (OR 0.61; 95% CI 0.45–0.82; p = 0.001) on day 14. Likewise, a systematic review of four RCTs for an American College of Physicians Practice Points [ 26 ] also claimed that remdesivir may reduce mortality with absolute risk difference (ARD) ranging from − 4 to 1% compared to the placebo. On day 28, however, there was no significant difference in mortality between the remdesivir and placebo groups.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis

2021

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Purpose This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19. Method Randomised controlled trials (RCTs) and observational studies reporting the effectiveness and safety of remdesivir were searched via databases and other sources from December 2019 to December 2020. Two independent reviewers performed literature screening, data extraction and assessment of risk bias. Seven studies involving 3686 patients were included. Results Treatment with remdesivir was associated with an increase in clinical recovery rate by 21% (RR 1.21; 95% CI 1.08–1.35) on day 7 and 29% (RR 1.29; 95% CI 1.22–1.37) on day 14. The likelihoods of requiring high-flow supplemental oxygen and invasive mechanical ventilation in the remdesivir group were lower than in the placebo group by 27% (RR 0.73; 95% CI 0.54–0.99) and 47% (RR 0.53; 95% CI 0.39–0.72), respectively. Remdesivir-treated patients showed a 39% (RR 0.61; 95% CI 0.46–0.79) reduction in the risk of mortality on day 14 compared to the control group; however, there was no significant difference on day 28. Serious adverse effects (SAEs) were significantly less common in patients treated with remdesivir, with an absolute risk difference of 6% (RD −0.06; 95% CI −0.09 to −0.03). Conclusion Despite conditional recommendation against its use, remdesivir could still be effective in early clinical improvement; reduction of early mortality and avoiding high-flow supplemental oxygen and invasive mechanical ventilation among hospitalised COVID-19 patients. Remdesivir was also well tolerated without significant SAEs compared to placebo, yet available evidence from clinical studies support the need to conduct close monitoring. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01671-0.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis

2021

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“…Role of povidone iodine is also coming up as a prophylactic agent ( Khan et al, 2020 ; Sarma et al, 2020b , 2020c , p. 2). Other agents under evaluation are remdesivir ( Rezagholizadeh et al, 2021 ) folic acid ( Bhattacharyya et al, 2021 , p. 19; Hardeep Kaur et al, 2021 ) etc. Various vaccine candidates are also under clinical trials for the same.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of dihydroorotate dehydrogenase (DHODH) inhibitors “leflunomide” and “teriflunomide” in Covid-19: A narrative review

Kaur

Sarma

Bhattacharyya

et al. 2021

European Journal of Pharmacology

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Dihydroorotate dehydrogenase (DHODH) is rate-limiting enzyme in biosynthesis of pyrimidone which catalyzes the oxidation of dihydro-orotate to orotate. Orotate is utilized in the biosynthesis of uridine-monophosphate. DHODH inhibitors have shown promise as antiviral agent against Cytomegalovirus, Ebola, Influenza, Epstein Barr and Picornavirus. Anti-SARS-CoV-2 action of DHODH inhibitors are also coming up. In this review, we have reviewed the safety and efficacy of approved DHODH inhibitors (leflunomide and teriflunomide) against COVID-19. In target-centered in silico studies, leflunomide showed favorable binding to active site of MPro and spike: ACE2 interface. In artificial-intelligence/machine-learning based studies, leflunomide was among the top 50 ligands targeting spike: ACE2 interaction. Leflunomide is also found to interact with differentially regulated pathways [identified by KEGG (Kyoto Encyclopedia of Genes and Genomes) and reactome pathway analysis of host transcriptome data] in cogena based drug-repurposing studies. Based on GSEA (gene set enrichment analysis ), leflunomide was found to target pathways enriched in COVID-19. In vitro , both leflunomide (EC50 41.49±8.8μmol/L) and teriflunomide (EC50 26μmol/L) showed SARS-CoV-2 inhibition. In clinical studies, leflunomide showed significant benefit in terms of decreasing the duration of viral shredding, duration of hospital stay and severity of infection. However, no advantage was seen while combining leflunomide and IFN alpha-2a among patients with prolonged post symptomatic viral shredding. Common adverse effects of leflunomide were hyperlipidemia, leucopenia, neutropenia and liver-function alteration. Leflunomide/teriflunomide may serve as an agent of importance to achieve faster virological clearance in COVID-19, however, findings needs to be validated in bigger sized placebo controlled studies.

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“… 34 A recent meta-analysis on the effectiveness of remdesivir described similar results. 35 Other treatment approaches that appear to lower mortality in critically ill patients are intravenous immunoglobulin, ivermectin, and tocilizumab. 34 This evidence, however, remains inconclusive.…”

Section: Resultsmentioning

confidence: 99%

Vitamin D regulation of the immune system and its implications for COVID-19: A mini review

et al. 2021

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The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is at the origin of the current pandemic, predominantly manifests with severe respiratory symptoms and a heightened immune response. One characteristic of SARS-CoV-2 is its capacity to induce cytokine storm leading to acute respiratory distress syndrome. Consequently, agents with the ability to regulate the immune response, such as vitamin D, could become tools either for the prevention or the attenuation of the most severe consequences of the coronavirus disease 2019 (COVID-19). Vitamin D has shown antimicrobial as well as anti-inflammatory properties. While SARS-CoV-2 promotes the release of proinflammatory cytokines, vitamin D attenuates the release of at least some of these same molecules. Inflammatory cytokines have been associated with the clinical phenomena of COVID-19 and in particular with its most dangerous complications. Therefore, the goals of this article are as follows: first, present the numerous roles vitamin D plays in modulating the immune response; second, gather data currently available on COVID-19 clinical presentation and its relation to cytokines and similar molecules; third, expose what it is known about how coronaviruses elicit an inflammatory reaction; and fourth, discuss the potential contribution of vitamin D in reducing the risk and severity of COVID-19.

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Remdesivir for treatment of COVID-19; an updated systematic review and meta-analysis

Cited by 95 publications

References 49 publications

Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis

Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis

Efficacy and safety of dihydroorotate dehydrogenase (DHODH) inhibitors “leflunomide” and “teriflunomide” in Covid-19: A narrative review

Vitamin D regulation of the immune system and its implications for COVID-19: A mini review

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