Effects of remdesivir on SARS-CoV-2 viral dynamics and mortality in viraemic patients hospitalized for COVID-19

Hagman et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkad295

Sep 2023

Retrospective 318 hospitalized COVID-19 patients in Sweden, showing improvements in viral clearance but no improvement for mortality with remdesivir treatment.

Gérard, Wu, Zhou show significantly increased risk of acute kidney injury with remdesivir.

1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

3. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

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risk of death, no change, HR 1.00, p = 0.97, treatment 105, control 213, adjusted per study, multivariable, day 60.

risk of death, no change, HR 1.00, p = 0.99, treatment 105, control 213, adjusted per study, multivariable, day 28.

risk of death, 20.0% lower, HR 0.80, p = 0.74, treatment 105, control 213, adjusted per study, multivariable, day 7.

risk of progression, 40.0% higher, OR 1.40, p = 0.31, treatment 105, control 213, adjusted per study, multivariable, Table S7, RR approximated with OR.

risk of no viral clearance, 28.6% lower, HR 0.71, p = 0.11, treatment 105, control 213, adjusted per study, inverted to make HR<1 favor treatment, multivariable.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Hagman et al., 26 Sep 2023, retrospective, Sweden, peer-reviewed, 9 authors, average treatment delay 6.0 days.

This Paper Remdesivir All

Effects of remdesivir on SARS-CoV-2 viral dynamics and mortality in viraemic patients hospitalized for COVID-19

Karl Hagman, Magnus Hedenstierna, Jacob Widaeus, Emelie Arvidsson, Berit Hammas, Lena Grillner, Jan Jakobsson, Patrik Gille-Johnson, Johan Ursing

doi:10.1093/jac/dkad295/7283037

Background: Studies on the antiviral effects of remdesivir have shown conflicting results. SARS-CoV-2 viraemia could identify patients in whom antiviral treatment may be particularly beneficial. Objectives: To investigate antiviral effects and clinical outcomes of remdesivir treatment in viraemic patients. Methods: Viraemic patients hospitalized for COVID-19 with ratio of arterial oxygen partial pressure to fractional inspired oxygen of ≤300, symptom duration ≤10 days, and estimated glomerular filtration rate ≥30 mL/min were included in a cohort. The rate of serum viral clearance and serum viral load decline, 60 day mortality and in-hospital outcomes were estimated. A subgroup analysis including patients with symptom duration ≤7 days was performed. Results: A total of 318 viraemic patients were included. Thirty-three percent (105/318) received remdesivir. The rate of serum viral clearance [subhazard risk ratio (SHR) 1.4 (95% CI 0.9-2.0), P = 0.11] and serum viral load decline (P = 0.11) were not significantly different between remdesivir-treated patients and controls. However, the rate of serum viral clearance was non-significantly higher [SHR 1.6 (95% CI 1.0-2.7), P = 0.051] and the viral load decline was faster (P = 0.03) in remdesivir-treated patients with symptom duration ≤7 days at admission. The 60 day mortality [HR 1.0 (95% CI 0.6-1.8), P = 0.97] and adverse in-hospital outcomes [OR 1.4 (95% CI 0.8-2.4), P = 0.31] were not significantly different between remdesivir-treated patients and controls. Conclusions: Remdesivir treatment did not significantly change the duration of SARS-CoV-2 viraemia, decline of serum viral load, 60 day mortality or in-hospital adverse outcomes in patients with ≤10 days of symptoms at admission. Remdesivir appeared to reduce the duration of viraemia in a subgroup of patients with ≤7 days of symptoms at admission.

Ethics The Swedish Ethical Review Authority approved of the study (registration numbers 2020-01770 and 2020-06337). Informed consent was waived. Author contributions Conceptualization: K.H., M.H., P.G.-J., J.U. Methodology: K.H., M.H., J.J., J.U. Investigation: K.H., J.W., M.H., E.A., B.H., L.G., J.U. Data curation: K.H., B.H., L.G., J.U. Formal analysis: K.H., J.U. Writing-original draft: K.H., J.U. Writing-review and editing: K.H., J.W., M.H., E.A., B.H., L.G., J.J., P.G.-J., J.U. Visualization: K.H., J.U. Supplementary data Figure S1 and Tables S1 to S8 are available as Supplementary data at JAC Online.

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Late treatment
is less effective

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