Effectiveness of remdesivir for hospitalized COVID-19 patients depending on the severity of respiratory status: a multicenter retrospective study in Japan

Abstract

Background: Remdesivir, an antiviral nucleotide analog prodrug, is approved for clinical use against COVID-19 worldwide. However, its effectiveness varies depending on the respiratory failure status of patients. This study aimed to evaluate the effectiveness of remdesivir treatment based on the severity of respiratory failure, as indicated by the oxygen demand upon hospital admission. Subgroups analyses were conducted to identify patient groups that might benefit from remdesivir treatment.

Methods: This retrospective observational study (the J-RECOVER) enrolled patients with COVID-19 from 64 institutions in Japan between January 1 and September 30, 2020. Patients aged ≥ 18 years who were administered remdesivir within 3 days of hospital admission were included. A total of 3,591 patients were included, and propensity score overlap weighting analysis was used to compare in-hospital mortality based on respiratory failure status at admission between remdesivir and control groups. Subgroup analyses identified specific patient populations that may benefit most from remdesivir treatment, considering factors such as respiratory status and renal function.

Results: The overlap weighting (OW)-adjusted odds ratio (OR) for mortality in overall cohort, mild cases without supplemental oxygen, moderate cases requiring supplemental oxygen, and severe cases requiring ventilation was (OR, 0.65 (95% confidence interval (CI), 0.36-1.19; P = 0.16), 0.11 (95% CI, 0.01-1.03; P = 0.05). 0.82 (95% CI, 0.31-2.16; P = 0.69), and 0.78 (95% CI, 0.28-2.17; P = 0.63), respectively. A trend toward improvement in mortality was observed in respiratory indicators, such as SpO2 ≥ 94% (OR, 0.43; 95% CI, 0.19-0.99; P = 0.04), oxygen support with FiO2 < 0.5 (OR, 0.40; 95% CI, 0.16-0.97; P = 0.04), and PFR ≥ 300 (OR, 0.17; 95% CI, 0.03-0.94; P = 0.04). Subgroup analyses indicated improved mortality in patients with an estimated glomerular filtration rate (eGFR) of > 60 mL/min per 1.73 m² (OR, 0.29; 95% CI, 0.09-0.94; P = 0.03), with a p-value for interaction of P = 0.18.

Conclusion: Remdesivir treatment may reduce the risk of in-hospital mortality in patients with mild respiratory distress. Subgroup analysis suggested that remdesivir treatment may improve mortality in patients with eGFR ≥ 60 mL/min per 1.73 m².

Keywords: COVID-19; Japan; Overlap weighting; Propensity score; Remdesivir; Respiratory status.

Fig. 1

Patient flow chart: Identification and selection of patients for inclusion. COVID-19, coronavirus disease 2019

Fig. 2

Forest plot of the comparison: remdesivir-treated group vs. control group: in-hospital mortality. In the subgroup analysis of respiratory status, p values for the interaction between mild and moderate/severe cases are shown. OR, odds ratio; CI, confidence interval; BMI, body mass index; SpO2, saturation of percutaneous oxygen; PaO2, partial pressure of oxygen in arterial blood; FiO2, fraction of inspiratory oxygen; PFR, partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen ratio; NEWS2, National Early Warning Score 2; SOFA, Sequential Organ Failure Assessment; eGFR, estimated glomerular filtration rate

Fig. 3

Kaplan–Meier Survival curves for remdesivir recipients and controls at each severity of respiratory status A overall. B Mild respiratory failure. C Moderate respiratory failure. D Severe respiratory failure The number “98” under “Number at Risk” represents the PS-adjusted patient count for each group. Since the propensity scores were recalculated separately for the overall cohort and each respiratory severity subgroup, the number of adjusted patients shown in panels B–D does not correspond to the total number shown in panel A