Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials

Al‐Abdouh, Ahmad; Bizanti, Anas; Barbarawi, Mahmoud; Jabri, Ahmad; Kumar, Ashish; Fashanu, Oluwaseun E.; Khan, Safi U.; Zhao, Di; Antar, Annukka A.R.; Michos, Erin D.

doi:10.1016/j.cct.2021.106272

Cited by 67 publications

(50 citation statements)

References 29 publications

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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%

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%

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

2021

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“…The scientific community has investigated multiple therapies for the prevention and/or treatment of COVID-19. This spectrum includes immunomodulatory antivirals, therapies with convalescent plasma or hyperimmune equine plasma, anticoagulants, antibiotics, renin angiotensin system inhibitors and glucocorticoids, among others [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial

Vallejos¹,

Zoni²,

Bangher³

et al. 2021

BMC Infect Dis

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients. Objective To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19. Design, setting and participants: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021. Intervention Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient’s weight, for 2 days. Main outcomes and measures The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points. Results The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3–6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32–1.31; p = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (p = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes. Limitations Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population. Conclusion Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes. Trial registration ClinicalTrials.gov NCT04529525.

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“…During the Covid-19 pandemic, repurposing of the existing drugs targeting RdRp, justified by structural similarity among RdRp active sites (Peersen, 2019), became an urgent priority. Among these drugs, remdesivir received the most attention even though the estimates of its clinical effectiveness range from moderate to insignificant (Al-Abdouh et al, 2021;Kaka et al, 2021). RdRp readily uses RTP as a substrate in place of ATP and temporarily stalls downstream from the site of RMP incorporation (Gordon et al, 2020;Kokic et al, 2021); however, the proposed mechanisms of its action vary widely, from RdRp stalling to RNA chain termination to disassembly of the RdRp (Bravo et al, 2021;Olotu et al, 2021;Tchesnokov et al, 2020).…”

Section: Crosstalk Between Two Catalytic Sites Of Sars-cov-2 Nsp12mentioning

confidence: 99%

Allosteric activation of SARS-CoV-2 RdRp by remdesivir triphosphate and other phosphorylated nucleotides

Wang

Svetlov

Wolf

et al. 2021

Preprint

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RNA-dependent RNA polymerase (RdRp) is a primary target for antivirals. We report that Nsp12, a catalytic subunit of SARS-CoV-2 RdRp, produces an inactive enzyme when codon-optimized for bacterial expression. We also show that accessory subunits, NTPs, and translation by slow ribosomes partially rescue Nsp12. Our findings have implications for functional studies and identification of novel inhibitors of RdRp and for rational design of other biotechnologically and medically important expression systems.

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Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials

Cited by 67 publications

References 29 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

Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial

Allosteric activation of SARS-CoV-2 RdRp by remdesivir triphosphate and other phosphorylated nucleotides

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