Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

Lee, Todd C.; Murthy, Srinivas; Corpo, Olivier Del; Senécal, Julien; Butler‐Laporte, Guillaume; Sohani, Zahra N.; Brophy, James M.; McDonald, Emily G.

doi:10.1016/j.cmi.2022.04.018

Cited by 65 publications

(56 citation statements)

References 21 publications

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“…The 131 patients in the remdesivir analysis mITT population had a median of 18 viral load measurements (range [16][17][18] each between days 0 and 7, of which 14.6% (343/2,356) were below the lower limit of detection (LOD). The baseline geometric mean (GM) oropharyngeal viral load was 3.5x10 5 RNA copies/mL (IQR 5.9x10 4 to 2.5x10 6 ).…”

Section: Remdesivirmentioning

confidence: 99%

“…Early in the COVID-19 pandemic casirivimab/imdevimab proved highly effective in prevention and early treatment of COVID-19 [1][2][3][4][5] , and showed life-saving efficacy in antibody negative hospitalized patients 6 . In contrast the initial evidence for parenteral remdesivir was unclear, and the WHO recommended against its use [7][8][9][10][11][12][13][14][15] , although this has recently changed 16,17 . Remdesivir is now widely recommended, whereas many regulatory authorities no longer recommend casirivimab/imdevimab.…”

Section: Introductionmentioning

confidence: 99%

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Clinical antiviral efficacy of remdesivir and casirivimab/imdevimab against the SARS-CoV-2 Delta and Omicron variants

Jittamala

Schilling

Watson

et al. 2022

Preprint

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Background: Uncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines. Early in the pandemic the monoclonal antibody cocktail, casirivimab/imdevimab, proved highly effective in clinical trials but because of weak or absent in vitro activity against the SARS-CoV-2 Omicron BA.1 subvariant, it is no longer recommended. Methods: In a multicenter open label, randomized, controlled adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days), casirivimab/imdevimab (600mg/600mg), and no study drug. The primary outcome was the viral clearance rate in the modified intention-to-treat population derived from daily log10 viral densities (days 0-7) in standardized duplicate oropharyngeal swab eluates. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). Results: Acceleration in mean estimated SARS-CoV-2 viral clearance, compared with the contemporaneous no study drug arm (n=64), was 42% (95%CI 18 to 73%) for remdesivir (n=67). Acceleration with casirivimab/imdevimab was 58% (95%CI: 10 to 120) in Delta (n=13), and 20% (95%CI: 3 to 43) in Omicron variant (n=61) infections compared with contemporaneous no study drug arm (n=84). In a post hoc subgroup analysis viral clearance was accelerated by 8% in BA.1 (95%CI: -21 to 59) and 23% (95%CI: 3 to 49) in BA.2 and BA.5 Omicron subvariants. Conclusions: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Despite substantially reduced in vitro activities, casirivimab/imdevimab retains in vivo antiviral activity against COVID-19 infections caused by currently prevalent Omicron subvariants.

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Section: Remdesivirmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical antiviral efficacy of remdesivir and casirivimab/imdevimab against the SARS-CoV-2 Delta and Omicron variants

Jittamala

Schilling

Watson

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…This adds to prior reports of a decrease in the mortality among hospitalized persons between COVID-19 waves ( 33 , 34 ), but our results indicate that this is especially pronounced in diabetes. The increased use of corticosteroids ( 35 ), prone positioning ( 36 ) and anti-viral treatment ( 37 ) during the pandemic could have had an impact on the risk of mortality in hospitalized persons. As the risk of severe COVID-19 infection is higher in persons with diabetes, a higher impact of advances in the treatment of severe COVID-19 would concomitantly be expected in persons with diabetes.…”

Section: Discussionmentioning

confidence: 99%

Risk of severe COVID-19 infection in persons with diabetes during the first and second waves in Denmark: A nationwide cohort study

et al. 2022

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ObjectiveCoronavirus disease-2019 (COVID-19) increases risk of hospitalization and death in diabetes and diabetes-related conditions. We examined the temporal trends in COVID-19-related hospitalization and mortality in the total Danish population by diabetes and diabetes-related conditions in the two first waves of COVID-19 in Denmark.Materials and methodsWe identified all persons with diabetes in the whole Danish population using national registries. COVID-19-related risks of hospitalization and death were assessed using Cox regression analysis in wave 1 (1 March-31 August 2020) and wave 2 (1 September 2020-28 February 2021) of the pandemic for persons with (n=321,933) and without diabetes (n=5,479,755). Analyses were stratified according to status of hypertension, obesity, cardiovascular and microvascular disease.ResultsThe cumulative incidence of COVID-19 hospitalization increased from wave 1 to wave 2 in both persons without (from 4 to 10 in 10,000) and with diabetes (from 16 to 54 per 10,000). The relative risk of hospitalization, however, increased more in patients with diabetes compared to persons without (age-, sex- and co-morbidity-adjusted HR [aHR] 1.40 (95% CI 1.27, 1.55) versus 1.76 (1.65, 1.87), p<0.001 for interaction with wave). The mortality rate, according to the whole population, increased similarly in persons without and with diabetes from wave 1 to wave 2 (from 0.63 to 1.5 versus from 4.3 to 10 in 10,000; aHR 1.65; 1.34, 2.03 and 1.64; 1.43, 1.88). However, when mortality was restricted to the hospitalized population, the crude mortality fell from 26.8% to 19.6% in persons with diabetes, while only a minor decrease was seen in persons without diabetes (from 16.7% to 15.5%).ConclusionThe risk of COVID-19-related hospitalization increased more in persons with than without diabetes from wave 1 to wave 2 of the COVID-19 pandemic in the Danish population. However, mortality according to the whole population did not change, due to reduced mortality among hospitalized persons with diabetes.

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“…we read with interest the systematic review and meta-analysis by Lee et al concerning remdesivir use for the treatment of patients with COVID-19. Authors conclude that there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy ( 1 ).…”

mentioning

confidence: 99%