Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study

Flisiak et al., Polish Archives of Internal Medicine, doi:10.20452/pamw.15735, SARSTer, Nov 2020

https://c19early.org/flisiak.html

Retrospective study comparing 122 remdesivir patients and 211 lopinavir/ritonavir patients, showing higher rates of clinical improvement with remdesivir and lower mortality (not statistically significant).

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.

risk of death, 48.9% lower, RR 0.51, p = 0.18, treatment 5 of 122 (4.1%), control 17 of 211 (8.1%), NNT 25, odds ratio converted to relative risk, all patients, day 28.

SpO₂<95%, 58.0% lower, RR 0.42, p = 0.13, treatment 4 of 82 (4.9%), control 14 of 119 (11.8%), NNT 15, odds ratio converted to relative risk.

no clinical improvement, 56.5% lower, RR 0.44, p = 0.01, treatment 9 of 122 (7.4%), control 36 of 211 (17.1%), NNT 10, odds ratio converted to relative risk.

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.

Flisiak et al., 3 Nov 2020, retrospective, Poland, peer-reviewed, 23 authors, study period 1 March, 2020 - 31 August, 2020, SARSTer trial. Contact: robert.flisiak1@gmail.com.

This Paper Remdesivir All

Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study

Robert Flisiak, Dorota Zarębska-Michaluk, Aleksandra Berkan-Kawińska, Magdalena Tudrujek-Zdunek, Magdalena Rogalska, Anna Piekarska, Dorota Kozielewicz, Krzysztof Kłos, Marta Rorat, Beata Bolewska, Anna Szymanek-Pasternak, Włodzimierz Mazur, Beata Lorenc, Regina Podlasin, Katarzyna Sikorska, Barbara Oczko-Grzesik, Cezary Iwaszkiewicz, Bartosz Szetela, Paweł Pabjan, Małgorzata Pawłowska, Krzysztof Tomasiewicz, Joanna Polańska, Jerzy Jaroszewicz

Polish Archives of Internal Medicine, doi:10.20452/pamw.15735

Remdesivir use in COVID-19 103 supportive care was available, but the rapid worldwide spread of COVID-19 has raised a desperate need to invent an antiviral agent active against SARS-CoV-2. At first, the search for an effective therapy focused on drug repurposing and new ways of using approved agents with confirmed activity against other viruses. Among them, a compound of lopinavir and ritonavir was identified. Lopinavir, acting as an inhibitor of human immunodeficiency virus (HIV) protease, coadministered with ritonavir to increase its bioavailability, was demonstrated to have in vitro activity against both SARS-CoVs and MERS-CoVs. 1-5 The positive impact of lopinavir / ritonavir on the clinical outcome and reduction of the viral load in nasopharyngeal swabs was documented in patients participating in an open-label study performed during the outbreak of SARS in 2003. 2,3 Three case reports and a single retrospective study focused Introduction In December 2019, a new pathogen associated with an outbreak of respiratory tract infections was discovered in Wuhan, China. It was identified as a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), closely related to the already known betacoronaviruses responsible for epidemics named with the acronyms SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). The outbreak of the disease cause by SARS-CoV-2, coronavirus disease 2019 (COVID-19), was announced a global pandemic by the World Health Organization (WHO) in March 2020. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic or mild, selflimited respiratory tract disease to severe progressive pneumonia leading to acute respiratory distress syndrome and death due to multiorgan failure. At the beginning of the epidemic, only

References

Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19 -preliminary report, N Engl J Med, doi:10.1056/NEJMc2022236

Cai, Yang, Liu, Experimental treatment with favipiravir for COVID-19: an open-label control study, Engineering, doi:10.1016/j.eng.2020.03.007

Cao, Wang, Wen, A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med, doi:10.1056/NEJMc2008043

Chan, Yao, Yeung, Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset, J Infect Dis, doi:10.1093/infdis/jiv392

Chen, Chan, Jiang, In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds, J Clin Virol, doi:10.1016/j.jcv.2004.03.003

Chu, Cheng, Hung, Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture, Antimicrob Agents Chemother, doi:10.1128/AAC.03011-14

Drożdżal, Rosik, Lechowicz, FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy, Drug Resist Updat, doi:10.1016/j.drup.2020.100719

Flisiak, Horban, Jaroszewicz, Management of SARS -CoV -2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists. Annex no. 1 as of June 8, 2020, Pol Arch Intern Med, doi:10.20452/pamw.15658

Flisiak, Horban, Jaroszewicz, Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists as of March 31, 2020, Pol Arch Intern Med, doi:10.20452/pamw.15424

Goldman, Lye, Hui, Remdesivir for severe COVID-19 versus a cohort receiving standard of care, Clin Infect Dis, doi:10.1056/NEJMoa2015301

Grein, Ohmagari, Shin, Compassionate use of remdesivir for patients with severe Covid-19, N Engl J Med

Infection ; Gilead, Merck, Roche, Berkan-Kawińska, particularly in patients with oxygen saturation ≤95%. ARTICLE InFORmATIOn ACknOwLEDgmEnTS The study was supported by the Polish Association of Epidemiologists and Infectiologists and Medical Research Agency

Kalil, Patterson, Mehta, Baricitinib plus remdesivir for hospitalized adults with Covid-19, N Engl J Med

Kim, Kim, Kwon, Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019, Korean J Intern Med, doi:10.3904/kjim.2020.224

Kim, Won, Kee, Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for the Middle East respiratory syndrome, Antivir Ther, doi:10.3851/IMP3002

Lamb, Remdesivir: first approval, doi:10.1007/s40265-020-01378-w

Lecronier, Beurton, Burrel, Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis, Crit Care, doi:10.1186/s13054-020-03117-9

Mulangu, Dodd, Rt, A randomized, controlled trial of Ebola virus disease therapeutics, N Engl J Med, doi:10.1056/NEJMoa1910993

Pan, Peto, Henao-Restrepo, Repurposed antiviral drugs for Covid-19 -interim WHO Solidarity trial results, N Engl J Med

Rivera, Peters, Panagiotou, Utilization of COVID-19 treatments and clinical outcomes among patients with cancer: a COVID-19 and Cancer Consortium (CCC19) cohort study, Cancer Discov, doi:10.1158/2159-8290.CD-20-0941

Sheahan, Sims, Graham, Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses, Sci Transl Med, doi:10.1126/scitranslmed.aal3653

Spanakis, Tsiodras, Haagmans, Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2014.07.026

Spinner, Gottlieb, Criner, Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial, JAMA

Tomasiewicz, Piekarska, Stempkowska-Rejek, Tocilizumab for patients with severe COVID-19: a retrospective, multi-center study, Expert Rev Anti Infect Ther, doi:10.1080/14787210.2020.1800453

Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0

Yamamoto, Yang, Yoshinaka, HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2004.04.083

DOI record: { "DOI": "10.20452/pamw.15735", "ISSN": [ "1897-9483" ], "URL": "http://dx.doi.org/10.20452/pamw.15735", "author": [ { "affiliation": [], "family": "Flisiak", "given": "Robert", "sequence": "first" }, { "affiliation": [], "family": "Zarębska-Michaluk", "given": "Dorota", "sequence": "additional" }, { "affiliation": [], "family": "Berkan-Kawińska", "given": "Aleksandra", "sequence": "additional" }, { "affiliation": [], "family": "Tudrujek-Zdunek", "given": "Magdalena", "sequence": "additional" }, { "affiliation": [], "family": "Rogalska", "given": "Magdalena", "sequence": "additional" }, { "affiliation": [], "family": "Piekarska", "given": "Anna", "sequence": "additional" }, { "affiliation": [], "family": "Kozielewicz", "given": "Dorota", "sequence": "additional" }, { "affiliation": [], "family": "Kłos", "given": "Krzysztof", "sequence": "additional" }, { "affiliation": [], "family": "Rorat", "given": "Marta", "sequence": "additional" }, { "affiliation": [], "family": "Bolewska", "given": "Beata", "sequence": "additional" }, { "affiliation": [], "family": "Szymanek-Pasternak", "given": "Anna", "sequence": "additional" }, { "affiliation": [], "family": "Mazur", "given": "Włodzimierz", "sequence": "additional" }, { "affiliation": [], "family": "Lorenc", "given": "Beata", "sequence": "additional" }, { "affiliation": [], "family": "Podlasin", "given": "Regina", "sequence": "additional" }, { "affiliation": [], "family": "Sikorska", "given": "Katarzyna", "sequence": "additional" }, { "affiliation": [], "family": "Oczko-Grzesik", "given": "Barbara", "sequence": "additional" }, { "affiliation": [], "family": "Iwaszkiewicz", "given": "Cezary", "sequence": "additional" }, { "affiliation": [], "family": "Szetela", "given": "Bartosz", "sequence": "additional" }, { "affiliation": [], "family": "Pabjan", "given": "Paweł", "sequence": "additional" }, { "affiliation": [], "family": "Pawłowska", "given": "Małgorzata", "sequence": "additional" }, { "affiliation": [], "family": "Tomasiewicz", "given": "Krzysztof", "sequence": "additional" }, { "affiliation": [], "family": "Polańska", "given": "Joanna", "sequence": "additional" }, { "affiliation": [], "family": "Jaroszewicz", "given": "Jerzy", "sequence": "additional" } ], "container-title": "Polish Archives of Internal Medicine", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 12, 31 ] ], "date-time": "2020-12-31T17:12:09Z", "timestamp": 1609434729000 }, "deposited": { "date-parts": [ [ 2020, 12, 31 ] ], "date-time": "2020-12-31T17:12:09Z", "timestamp": 1609434729000 }, "indexed": { "date-parts": [ [ 2023, 3, 27 ] ], "date-time": "2023-03-27T10:29:37Z", "timestamp": 1679912977789 }, "is-referenced-by-count": 6, "issued": { "date-parts": [ [ 2020, 12, 31 ] ] }, "link": [ { "URL": "https://www.mp.pl/paim/en/node/15735/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "8469", "original-title": [], "prefix": "10.20452", "published": { "date-parts": [ [ 2020, 12, 31 ] ] }, "published-print": { "date-parts": [ [ 2020, 12, 31 ] ] }, "publisher": "Medycyna Praktyczna", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://www.mp.pl/paim/issue/article/15735" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Internal Medicine" ], "subtitle": [], "title": "Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study", "type": "journal-article" }

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0