Recent increases in COVID-19 case numbers and the emergence of new variants, such as BA.2.86, demonstrate just how important it is to stay informed about the infection and available treatment options.
Conditional recommendations for COVID-19 treatments from the National Institute for Health and Care Excellence have created a gap between guideline recommendations and current practice, resulting in variations across NHS trusts. In this recorded webinar — delivered live on 7 September 2023 — three experts unpick current guidelines to improve their interpretation and implementation to support pharmacists’ decision making relating to the appropriate and effective use of antivirals in practice.
The session covers:
- Clinical-trial and real-world data on the efficacy of available antivirals;
- Available antivirals and considerations relevant for their use in practice, including when COVID-19 antivirals are indicated and which patients are most likely to benefit from their use;
- Guidelines that underpin antiviral use and how they are being, and should be, applied in practice.
Thank you to our guest speakers Stephen Griffin, professor of cancer virology, Leeds Institute of Medical Research, School of Medicine, University of Leeds, and co-chair of the Independent Scientific Advisory Group for Emergencies; and Prijay Bakrania and Rebecca Steed, specialist clinical pharmacists — infectious diseases and COVID services, Guy’s and St Thomas’ NHS Foundation Trust, for their insight and presentations.
The webinar was hosted by Caitlin Killen, assistant clinical editor at The Pharmaceutical Journal.
Additional question for the experts from an attendee
Q. For treating children with COVID-19 who fit the high-risk criteria, is there work in the pipeline for getting Paxlovid licensed for the <18 years cohort (as currently in the United States, Paxlovid is licensed by the US Food and Drug Administration for children who are >12 years and >40 kg)?
A. We do not have any additional information on Pfizer’s plans regarding licensing Paxlovid in children. Ongoing clinical trials in this area (e.g. ClinicalTrials.gov identifiers: NCT05261139, NCT05438602, NCT05567952 and NCT05263908) will hopefully provide further evidence.
Abdelnabi R, Jochmans D, Donckers K et al. Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment. Nat Commun 2023;14:2124. doi: 10.1038/s41467-023-37773-6
Ader F, Bouscambert-Duchamp M, Hites M et al. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Infect Dis 2022;22(2):209–221. doi: 10.1016/S1473-3099(21)00485-0
Amanai B, Akbarzadeh A, Amani B et al. Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID-19: A systematic review and meta-analysis. J Med Virol 2023;95:e28889. doi: 10.1002/jmv.28889
Bae EY, Sanders JM, Johns ML et al. Therapeutic Options for Coronavirus Disease 2019 (COVID-19): Where Are We Now? Curr Infect Dis Rep 2021;23;28. doi: 10.1007/s11908-021-00769-8
Beigel JH, Tomashek KM, Dodd LE et al. Remdesivir for the treatment of Covid-19 — Final report. N Engl J Med 2020;383:1813–1826. doi: 10.1056/NEJMoa2007764
Bernal AJ, Gomes Da Silva MM, Musungaie DB et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med 2022;386:509–520. doi: 10.1056/NEJMoa2116044
Boras B, Jones RM, Anson BJ et al. Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19. Nat Commun 2021;12:6055. doi: 10.1038/s41467-021-26239-2
Butler CC, Hobbs FDR, Gbinigie OA et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2023;401(10373):281–293. doi: 10.1016/S0140-6736(22)02597-1
Coalition for Epidemic Preparedness Innovations. 100 Days Mission. 2023. Available at: https://100days.cepi.net/
Department of Health and Social Care. Defining the highest risk clinical subgroups upon community infection with SARS-CoV-2 when considering the use of neutralising monoclonal antibodies (nMABs) and antiviral drugs. 2023. Available at: https://www.gov.uk/government/publications/higher-risk-patients-eligible-for-covid-19-treatments-independent-advisory-group-report-march-2023/defining-the-highest-risk-clinical-subgroups-upon-community-infection-with-sars-cov-2-when-considering-the-use-of-neutralising-monoclonal-antibodies
Gandhi S, Klein J, Robertson AJ et al. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report. Nat Commun 2022;13:1547. doi: 10.1038/s41467-022-29104-y
Hammond J, Leister-Tebbe H, Gardner A et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med 2022;386:1397–1408. doi: 10.1056/NEJMoa2118542
Hettle D, Hutchings S, Muir P & Moran E. COVID-19 Genomics UK (COG-UK) consortium. Persistent SARS-CoV-2 infection in immunocompromised patients facilitates rapid viral evolution: Retrospective cohort study and literature review. Clin Infect Pract 2022;16:100210. doi: 10.1016/j.clinpr.2022.100210
Heyer A, Günther T, Robitaille A et al. Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection. Cell Rep Med 2022;3(9):100735. doi: 10.1016/j.xcrm.2022.100735
Iketani S, Mohri H, Culbertson B et al. Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir. bioRxiv [Preprint]. 2022 Aug 18:2022.08.07.499047. doi: 10.1101/2022.08.07.499047
Iketani S, Mohri H, Culbertson B et al. Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir. Nature 2023;613:558–564. doi: 10.1038/s41586-022-05514-2
Ip JD, Chu AW, Chan MW et al. Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance. eBiomedicine 2023:91;104559. doi: 10.1016/j.ebiom.2023.104559
Jin Z, Du X, Xu Y et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020;582:289–293. doi: 10.1038/s41586-020-2223-y
Katzenmaier S, Markert C, Riedel KD et al. Determining the time course of CYP3A inhibition by potent reversible and irreversible CYP3A inhibitors using A limited sampling strategy. Clin Pharmacol Ther 2011;90(5):666–673. doi: 10.1038/clpt.2011.164
Li G, Hilgenfeld R, Whitley R et al. Therapeutic strategies for COVID-19: progress and lessons learned. Nat Rev Drug Discov 2023;22:449–475. doi: 10.1038/s41573-023-00672-y
Moghadasi SA, Heilmann E, Khalil AM et al. Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors. bioRxiv [Preprint]. 2022 doi: 10.1101/2022.08.07.503099. Update in: Sci Adv. 2023;9(13):eade8778. PMID: 35982678; PMCID: PMC9387136
NHS England. Rapid Policy Statement. Interim Clinical Commissioning Policy: remdesivir and molnupiravir for non-hospitalised patients with COVID-19. 2023. Available at: https://www.england.nhs.uk/coronavirus/community-treatments/
NHS England. Rapid Policy Statement. Interim Clinical Commissioning Policy: Remdesivir for patients hospitalised due to COVID-19. 2022. Available at: https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103220.
National Institute for Health and Care Excellence. Casirivimab plus imdevimab, nirmatrelvir plus ritonavir, sotrovimab and tocilizumab for treating COVID-19. Technology appraisal guidance [TA878]. 2023. Available at: https://www.nice.org.uk/guidance/ta878
National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. NICE guideline [NG191]. 2023. Available at: https://www.nice.org.uk/guidance/ng191
National Institute for Health and Care Excellence. Molnupiravir, remdesivir and tixagevimab plus cilgavimab for treating COVID-19 [ID6261]. In development [GID-TA11297]. Last updated: 05 July 2023. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-ta11297
Sanderson T, Hisner R, Donovan-Banfield I et al. Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases. medRxiv 2023. doi: 10.1101/2023.01.26.23284998
Stader F, Khoo S, Stoeckle M et al. Stopping lopinavir/ritonavir in COVID-19 patients: duration of the drug interacting effect. J Antimicrob Chemother 2020;75(10):3084–3086. doi: 10.1093/jac/dkaa253
Stevens LJ, Pruijssers AJ, Lee HW et al. Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms. Sci Transl Med 2022 3;14(656):eabo0718. doi: 10.1126/scitranslmed.abo0718
Trottier CA, Wong B, Kohli R et al. Dual Antiviral Therapy for Persistent Coronavirus Disease 2019 and Associated Organizing Pneumonia in an Immunocompromised Host. Clinical Infectious Diseases 2023: 76(5):923–925. doi: 10.1093/cid/ciac847
UK Health Security Agency. National flu and COVID-19 surveillance reports: 2022 to 2023 season. 2023. Available at: https://www.gov.uk/government/statistics/national-flu-and-covid-19-surveillance-reports-2022-to-2023-season
University of Liverpool. COVID-19 Drug interactions checker. 2023. Available at: https://www.covid19-druginteractions.org/checker
WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results. N Engl J Med 2021;384:497–511. doi: 10.1056/NEJMoa2023184
Xie Y, Choi T & Al-Aly Z. Association of Treatment With Nirmatrelvir and the Risk of Post–COVID-19 Condition. JAMA Intern Med 2023;183(6):554–564. doi: 10.1001/jamainternmed.2023.0743
Zhou Y, Gammeltoft KA, Ryberg LA et al. Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system. Sci Adv 2022;8(51):eadd7197. doi: 10.1126/sciadv.add7197