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

Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321, Aug 2020

https://c19early.org/pasquinis.html

Retrospective 51 ICU patients under mechanical ventilation, 25 treated with remdesivir, showing lower mortality with treatment.

Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury with remdesivir. Leo, Briciu, Muntean, Petrov show increased risk of liver injury with remdesivir.

Remdesivir efficacy disappears with longer followup. Mixed-effects meta-regression of efficacy as a function of followup duration across all remdesivir studies shows decreasing efficacy with longer followup11. This may reflect antiviral efficacy being offset by serious adverse effects of treatment.

Important missing comments or errors? Let us know.

Study covers HCQ and remdesivir.

risk of death, 16.2% lower, RR 0.84, p = 0.03, treatment 14 of 25 (56.0%), control 24 of 26 (92.3%), NNT 2.8, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, multivariate.

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

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. 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.

3. 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.

4. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

5. Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

7. Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.sciencedirect.com, doi.org.

8. Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.mdpi.com, doi.org.

9. Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.mdpi.com, doi.org.

10. Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.risksafety.ru, doi.org.

11. c19early.org, c19early.org/smeta.html.c19early.org/smeta.html.

Pasquini et al., 23 Aug 2020, retrospective, Italy, peer-reviewed, 9 authors.

This Paper Remdesivir All

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

Zeno Pasquini, Roberto Montalti, Chiara Temperoni, Benedetta Canovari, Mauro Mancini, Michele Tempesta, Daniela Pimpini, Nicoletta Zallocco, Francesco Barchiesi

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321

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.

Transparency declarations None to declare.

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DOI record: { "DOI": "10.1093/jac/dkaa321", "ISSN": [ "0305-7453", "1460-2091" ], "URL": "http://dx.doi.org/10.1093/jac/dkaa321", "abstract": "Abstract\n \n Background\n 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.\n \n \n Methods\n 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.\n \n \n Results\n 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 &lt; 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 &lt; 0.001).\n \n \n Conclusions\n In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. 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Late treatment
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