Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care

Abstract

Background We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe COVID-19 using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard-of-care. Methods GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed SARS-CoV-2 infection, were hospitalized, had oxygen saturation 94% or lower on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard-of-care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. Results After the inverse probability of treatment weighting procedure 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio 2.03: 95% confidence interval 1.34–3.08, p<0.001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (adjusted odds ratio 0.38, 95% confidence interval: 0.22–0.68, p=0.001). Conclusions In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19.

Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review

“…Remdesivir was recently authorised for emergency use by the U.S. Food and Drug Administration (FDA), according to the results of a recent RCT [41], and of an openlabel trial [42], based on its effectiveness to significantly reduce the time to recovery, the recovery rate, and the mortality in patients with moderate-to-severe COVID-19 pneumonia [74]. Moreover, remdesivir has been included in the most recent guidelines of National Institute of Health (NIH), USA, for the treatment of COVID-19 patients with mild-moderate disease needing supplemental oxygen, but not requiring high-flow oxygen [75].…”

“…In a recent open-label, randomized trial [42], 312 patients receiving remdesivir added to the SOC for 5 or 10 days were compared with 818 matched controls treated with SOC therapy. The recovery rate was significantly higher in the remdesivir arm compared with controls (74.4% vs 59%; adjusted OR: 2.03; 95% CI 1.34-3.08; p < 0.001).…”

The therapeutic effect and safety of the drugs for COVID-19: a systematic review and meta-analysis

“…Moreover, in spite of the signi cant clinical improvement in antiviral medicine, the heterogeneity still needs to be noticed. I 2 value of 61% indicated the heterogeneity existed, so we removed the studies one by one and found that after removing the study of Olender, S. A, et al 32 , the I 2 value became 0%, demonstrating this study might be the source of heterogeneity. Immediately, we made the comparison among studies involved in analysis of clinical improvement rate and revealed that all studies are RCTs except for Olender, S. A, et al, re ecting unprecise control conditions and lack of blind method settings played the important role in heterogeneity.…”

“…The screening process was shown in figure 1 and 3860 studies were identified according to the research strategy initially. In total, 22 studies containing 12795 patients were adopted in our study and all of them were published in English 10,12,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] . Among trails included, half of them were RCTs, and the other were Non-RCTs.…”

Thoughts From the Trenches: Should We Look at the “Healthy”?

“…The war against this serious disease, as previously discussed, is still being waged without truce. This fight will provide relevant information for new patients with severe COVID19 manifestations: identifying prognostic factors for disease severity and progression to ARDS (12,13), and determine the real efficacy of therapeutic options through well-designed clinical trials (14). The study of mild cases of the disease and the asymptomatic carriers might help us answer other relevant questions, such as the duration of the contagious period, the characteristics of the non-severe disease or even the type, intensity and duration of immunization (8).…”