Remdesivir and Mortality in Patients With Coronavirus Disease 2019

Abstract

Background: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19.

Methods: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital.

Results: A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31-.69) in the univariate model (P < .001) and 0.60 (.40-.90) in the risk-adjusted model (P = .01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39-1.00; P = .049).

Conclusion: Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.

Keywords: COVID-19; Mortality; Remdesivir; SARS-CoV-2; Standard of Care.

Figure 1.

Study enrollment diagram. Abbreviations: BSC, best supportive care; COVID-19, coronavirus disease 2019; HCQ, hydroxychloroquine; PCR, polymerase chain reaction; RDV, remdesivir; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SpO₂, oxygen saturation; ULN, upper limit of normal; WHO-OSS, World Health Organization ordinal scale score for disease severity.

Figure 2.

Individual patient course by study group. Swimmers plots represent clinical course for entire study cohort. Patients are included in the groups for remdesivir (RDV) or hydroxychloroquine (HCQ) if they received ≥1 dose of RDV or HCQ, respectively, and included in the group for best supportive care (BSC) if they received neither. First doses of RDV are HCQ is indicated by black dots. Within in each group, rows represent the clinical course for an individual patient, shown by the daily World Health Organization ordinal scale score for disease severity (WHO-OSS), captured as the maximum score for each calendar day. The last observation after hospitalization is carried forward to the next in-person encounter, except for patients lost to follow-up, represented in white for missing. Missing data within the hospitalization (n = 175 of 12 354 days) is carried forward from the most recent observation. Participants are ordered by vital status (dead or alive), and within each group, by descending total WHO-OSS, summed over the 30-day interval.

Figure 3.

Unadjusted (A) and adjusted (B) Kaplan-Meier survival curves comparing all-cause mortality rates in hospitalized patients with coronavirus disease 2019 pneumonia treated with remdesivir (RDV), hydroxychloroquine (HCQ), and best supportive care (BSC). Twenty-two patients were excluded from adjusted Kaplan-Meier survival analyses owing to missingness of the risk-adjusted factors. Abbreviation: WHO-OSS, World Health Organization ordinal scale score for disease severity.