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The effects of remdesivir on long-term symptoms in patients hospitalised for COVID-19: a pre-specified exploratory analysis

Patrick-Brown et al., Communications Medicine, doi:10.1038/s43856-024-00650-4, NOR-Solidarity, NCT04321616
Nov 2024  
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Long-term results for the NOR-Solidarity RCT showing worse long-term outcomes at 3 months with remdesivir compared to SoC with or without HCQ. The CAT total score was 16.8 vs. 11.4, p = 0.06, close to statistical significance for harm. Sensitivity analysis using complete case results shows statistically significant worse shortness of breath with remdesivir (p = 0.03).
Gérard, Zhou, Wu, Kamo, Choi, Kim show significantly increased risk of acute kidney injury with remdesivir.
Patrick-Brown et al., 12 Nov 2024, Randomized Controlled Trial, Norway, peer-reviewed, 9 authors, study period 28 March, 2020 - 4 October, 2020, trial NCT04321616 (history) (NOR-Solidarity). Contact: d.j.patrick-brown@medisin.uio.no, i.c.olsen@medisin.uio.no.
This PaperRemdesivirAll
The effects of remdesivir on long-term symptoms in patients hospitalised for COVID-19: a pre-specified exploratory analysis
Thale D J Hovdun Patrick-Brown, Andreas Barratt-Due, Marius Trøseid, Anne Ma Dyrhol-Riise, Katerina Nezvalova-Henriksen, Trine Kåsine, Pål Aukrust, Inge C Olsen
Communications Medicine, doi:10.1038/s43856-024-00650-4
Background There is an unmet need for treatment of long-term symptoms following COVID-19. Remdesivir is currently the only antiviral approved by the European Medicines Agency for hospitalised patients. Here, we report on the effect of remdesivir in addition to standard of care on long-term symptoms and quality of life in hospitalised patients with COVID-19 as part of the open-label randomised NOR-Solidarity trial (NCT04321616). Methods A total of 185 patients were included in the main trial, of which 118 (60%) were randomised to either remdesivir (n = 42; 36%) or a post-hoc defined control group composed of patients who received standard of care alone or standard of care with hydroxychloroquine (n = 76; 64%). Participants were given quality of life surveys to fill out to gauge their self-reported health over time (the COPD assessment test, the EQ-5D-5L and the RAND SF-36). Results Here we show that after three months, patients treated with remdesivir do not show significant improvements in stated health compared to those who were not. There are selfreported symptoms of fatigue [mean remdesivir group 2.6 (standard deviation 1.5) v control 2.1 (1.6), 95% confidence interval(CI) -1.17 to 0.15, p = 0.129], shortness of breath [3.0 (1.7) v 2.1 (1.8), 95% CI -1.53 to 0.16, p = 0.110] and coughing [1.8 (1.6) v 1.2 (1.5), 95% CI -1.3 to 0.33, p = 0.237] 3 months after randomisation assessed via the COPD Assessment Test. Conclusions Our findings indicate that treatment with remdesivir during hospitalisation does not provide any clinically relevant long-term benefit. COVID-19, caused by the SARS-CoV-2 virus, was first identified in Wuhan, China in December 2019 1 , and emerged as a global pandemic around January 2020 2 . In response to this international threat, the World Health Organisation (WHO) mobilised its resources to recommend strategies for prevention and, as the pandemic progressed, identification of drugs that should be examined for their efficacy for treatment of this quickly evolving virus. The NOR-Solidarity trial was an independent add-on open-label randomised clinical trial to the WHO Solidarity trial, assessing the efficacy of hydroxychloroquine and remdesivir in addition to standard of care (SoC) (WHO Solidarity ClinicalTrials.gov ID NCT04315948; NOR-Solidarity
Author contributions P.A., A.M.D.R. and A.B.D. were responsible for the conceptualisation, methodology, acquisition of resources, supervision, and project administration. P.A., M.T., A.M.D.R., A.B.D. and T.K. were responsible for investigation. I.C.O. was responsible for conceptualisation, methodology, formal analysis, data curation, and writing (original draft preparation, review, and editing). T.P.B. was responsible for writing (original draft preparation, review, and editing), visualisation, and formal analysis. P.A., M.T., A.M.D.R., A.B.D., K.N.H. and T.K. were responsible for writing (review). Competing interests None of the authors declare any competing interests. The formal sponsor, Oslo University Hospital, was not directly (other than as an employer of the study group) involved in any of the study stages including study design, data analysis or manuscript preparation. Additional information Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s43856-024-00650-4 . Correspondence and requests for materials should be addressed to Thale D. J. Hovdun Patrick-Brown or Inge C. Olsen. Peer review information Communications Medicine thanks Viet-Thi Tran, Guillaume Lingas and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Reprints and permissions information is available at http://www.nature.com/reprints Publisher's note Springer..
References
Amstutz, Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data metaanalysis of randomised controlled trials, Lancet Respir. Med
Bajema, Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. veterans: target trial emulation studies with one-month and six-month outcomes, Ann. Intern. Med
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Beigel, Remdesivir for the treatment of Covid-19 -final report, N. Engl. J. Med
Boglione, Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?, QJM
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Huang, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Kim, Long COVID prevalence and impact on quality of life 2 years after acute COVID-19, Sci Rep
Kon, Minimum clinically important difference for the COPD Assessment Test: a prospective analysis, Lancet Respir. Med
Nevalainen, Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial, Nat Commun
Olsen, Barrat-Due, Nor-Solidarity: Patient Reported Outcome Measures paper, doi:10.17605/OSF.IO/HGRVP
Sun, Liu, Li, Wang, Liu, Impact of Long COVID on Health-Related Quality of Life Among Patients After Acute COVID-19 Infection: A Cross-Sectional Study, Inquiry
Tang, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Tompsett, Leacy, Moreno-Betancur, Heron, White, On the use of the not-at-random fully conditional specification (NARFCS) procedure in practice, Stat. Med
Xie, Choi, Al-Aly, Association of Treatment With Nirmatrelvir and the Risk of Post-COVID-19 Condition, JAMA Intern. Med
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Late treatment
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