Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU

Abstract

Background Remdesivir is a prodrug with in vitro activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical efficacy in patients with COVID-19 under mechanical ventilation remains to be evaluated. Methods This study includes patients under mechanical ventilation with confirmed SARS-CoV-2 infection admitted to the ICU of Pesaro hospital between 29 February and 20 March 2020. During this period, remdesivir was provided on a compassionate use basis. Clinical characteristics and outcome of patients treated with remdesivir were collected retrospectively and compared with those of patients hospitalized in the same time period. Results A total of 51 patients were considered, of which 25 were treated with remdesivir. The median (IQR) age was 67 (59–75.5) years, 92% were men and symptom onset was 10 (8–12) days before admission to ICU. At baseline, there was no significant difference in demographic characteristics, comorbidities and laboratory values between patients treated and not treated with remdesivir. Median follow-up was 52 (46–57) days. Kaplan–Meier curves showed significantly lower mortality among patients who had been treated with remdesivir (56% versus 92%, P < 0.001). Cox regression analysis showed that the Charlson Comorbidity Index was the only factor that had a significant association with higher mortality (OR 1.184; 95% CI 1.027–1.365; P = 0.020), while the use of remdesivir was associated with better survival (OR 3.506; 95% CI 1.768–6.954; P < 0.001). Conclusions In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. The use of remdesivir was associated with a significant beneficial effect on survival.

Remdesivir for treatment of COVID-19; an updated systematic review and meta-analysis

“…Then, 315 records were excluded with reasons, including studies that were in-vitro/in-silico/animal experiments (n=96), investigating other medications (n=93), evaluating other diseases (n=68), review/systematic review and meta-analysis/editorial/commentary (n=18), irrelevant (n=17), unfinished/terminated/suspended clinical trials (n=13), duplicates (n=8), or case reports (n=2). Finally, ten studies, including five RCTs ( Beigel et al, 2020b ; Goldman et al, 2020 ; Pan et al, 2020 ; Spinner et al, 2020 ; Wang et al, 2020 ) and five NRSIs ( Antinori et al, 2020 ; Fried et al, 2020 ; Grein et al, 2020 ; Olender et al, 2020 ; Pasquini et al, 2020 ), were entered into the meta-analysis ( Fig. 1 ).…”

Remdesivir: A potential game-changer or just a myth? A systematic review and meta-analysis

“…Exclusion Receiving medications that may potentially treat COVID-19 at entry but some received these treatments during the study. Patients on mechanical ventilation at screening Standard of care treatment (subject to clinical practice stipulated by individual sites) plus remdesivir 200 mg on day 1, followed by remdesivir 100 mg daily on days 2–5 Standard-of-care plus remdesivir 200 mg on day 1, followed by remdesivir 100 mg daily on days 2–10 (remdesivir-cohort) Remdesivir cohort obtained from Phase 3 randomized trial Non remdesivir cohort obtained from retrospective cohort study At Day 14 Remdesivir cohort 74.4% recovered, OR 2.03, 95% CI 1.34–3.08 Non Remdesivir cohort 59% recovered Mortality at day 14 OR 0.38, 95% CI 0.22–0.68 7.6% in remdesivir cohort vs 12.5% in the non-remdesivir cohort Pasquini et al [ 14 ], retrospective observational study, Italy N = 51 T = 25C = 26 M = 47 F = 4 Median age = 47 Inclusion criteria Age more than 18 years Positive RT-PCR essay Severe respiratory failure with the need for mechanical ventilation Exclusion criteria Mortality within the first 48 h First dose of 200 mg IV on Day 1, plus 100 mg daily from Day 2 to Day 10 in the treatment group Concomitant therapies include hydroxychloroquine, tocilizumab and lopinavir/ritonavir Better survival with remdesivir using Charlson Comorbidity Index OR 3.506 (95% CI 1.768–6.954) Median follow up 52 days (46–57) AE: Adverse Effect; ALT: Alanine Transaminase; AST: Aspartate Transaminase; C: Control; CI: Confidence Interval; CT: Computed Tomography; D7: Day7; D14: Day 14; D28: Day 28; ECMO: Extra Corporeal Membrane Oxygenation; F: Female; FiO2: Fraction of Inspired Oxygen; ICU: Intensive Care Unit; IV: Intravenous; IQR: Interquartile Range; LOS: Length of Stay; M: Male; N: Number; OR: Odd's Ratio; PaO2: Partial pressure of oxygen; RT-PCR: Reverse Transcription Polymerase Chain Reaction; T: Treatment; T5: 5 days treatment group; T10: 10 days treatment group; USA: United States of America. …”

Comment on: Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU

“…We read with great interest the paper by Pasquini et al . 1 supporting the effectiveness of remdesivir in improving the survival of critically ill patients with COVID-19. However, we think that the results obtained by the authors need to be interpreted cautiously because of their possible serious biases.…”