Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study.

Azvudine COVID-19 Molnupiravir Nirmatrelvir/ritonavir Retrospective study

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
09 Feb 2024
Historique:
received: 21 07 2023
accepted: 06 02 2024
medline: 10 2 2024
pubmed: 10 2 2024
entrez: 10 2 2024
Statut: epublish

Résumé

This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9-11) vs. 11 (95% CI 10-12) vs. 9 (95% CI 8-12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8-10) vs. 10 (95% CI 9.48-11) vs. 8.708 (95% CI 7.51-11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11-13) vs. 13 (95% CI 12-14) vs. 12 (95% CI 10-14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs.

Identifiants

pubmed: 38337014
doi: 10.1038/s41598-024-53862-y
pii: 10.1038/s41598-024-53862-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3318

Subventions

Organisme : Key Research & Developmenta Program of Hunan Province
ID : 2022SK2047
Organisme : Key Research & Developmenta Program of Hunan Province
ID : 2020SK3014
Organisme : Natural Science Foundation of Changsha city
ID : kq2208448

Informations de copyright

© 2024. The Author(s).

Références

Wiersinga, W. J., Rhodes, A., Cheng, A. C., Peacock, S. J. & Prescott, H. C. Pathophysiology, transmission, diagnosis, and treatment of Coronavirus Disease 2019 (COVID-19): A review. JAMA 324, 782–793 (2020).
doi: 10.1001/jama.2020.12839 pubmed: 32648899
World Health Organization. COVID-19 Weekly Epidemiological Update. Edition 140 published 27 April 2023. https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---27-april-2023 . Accessed May 2, 2023. (World health Organization, Geneva, 2023).
Koelle, K., Martin, M. A., Antia, R., Lopman, B. & Dean, N. E. The changing epidemiology of SARS-CoV-2. Science 375, 1116–1121 (2022).
doi: 10.1126/science.abm4915 pubmed: 35271324 pmcid: 9009722
Rothan, H. A. & Byrareddy, S. N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 109, 102433 (2020).
doi: 10.1016/j.jaut.2020.102433 pubmed: 32113704 pmcid: 7127067
China CDC. National Novel Coronavirus Infection Epidemic Situation. https://www.chinacdc.cn/jkzt/crb/zl/szkb_11803/jszl_13141/202304/t20230429_265709.html . Accessed June 14, 20232023.
Qu, P. et al. Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA2752. Cell Host Microbe 31, 9–17 (2023).
doi: 10.1016/j.chom.2022.11.012 pubmed: 36476380
Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186, 279-286 e278 (2023).
doi: 10.1016/j.cell.2022.12.018 pubmed: 36580913 pmcid: 9747694
Ren, S. Y., Wang, W. B., Gao, R. D. & Zhou, A. M. Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission, and vaccine resistance. World J. Clin. Cases 10, 1–11 (2022).
doi: 10.12998/wjcc.v10.i1.1 pubmed: 35071500 pmcid: 8727245
Niu, B., Ji, S., Zhao, S. & Lei, H. Timing and magnitude of the second wave of the COVID-19 Omicron variant—189 Countries and Territories, November 2021 to February 2023. China CDC Wkly. 5, 397–401 (2023).
doi: 10.46234/ccdcw2023.076 pubmed: 37197175 pmcid: 10184472
Consortium, W. H. O. S. T. et al. (2021) Repurposed antiviral drugs for Covid-19—Interim WHO solidarity trial results. N. Engl. J. Med. 384, 497–511.
Dryden-Peterson, S. et al. Nirmatrelvir plus ritonavir for early COVID-19 in a large U.S. Health system: A population-based cohort study. Ann. Intern. Med. 176, 77–84 (2023).
doi: 10.7326/M22-2141 pubmed: 36508742
Vassilopoulos, A. & Mylonakis, E. In patients with COVID-19 at risk for severe disease, nirmatrelvir + ritonavir reduced hospitalization or death. Ann. Intern. Med. 175, JC63 (2022).
doi: 10.7326/J22-0038 pubmed: 35667068
Hammond, J. et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N. Engl. J. Med. 386, 1397–1408 (2022).
doi: 10.1056/NEJMoa2118542 pubmed: 35172054
Jayk Bernal, A. et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N. Engl. J. Med. 386, 509–520 (2022).
doi: 10.1056/NEJMoa2116044 pubmed: 34914868
Khoo, S. H. et al. Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): A randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Infect. Dis. 23, 183–195 (2023).
doi: 10.1016/S1473-3099(22)00644-2 pubmed: 36272432
Butler, C. C. 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 401, 281–293 (2023).
doi: 10.1016/S0140-6736(22)02597-1 pubmed: 36566761
Zhang, J.-L. et al. Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients. Signal Transduct. Target. Ther. 6, 414 (2021).
doi: 10.1038/s41392-021-00835-6 pubmed: 34873151 pmcid: 8646019
Ren, Z. et al. A randomized, open-label, controlled clinical trial of azvudine tablets in the treatment of mild and common COVID-19, a pilot study. Adv. Sci. (Weinheim, Baden-Wurttemberg, Germany) 7, e2001435 (2020).
da Silva, R. M. et al. Serial viral load analysis by DDPCR to evaluate FNC efficacy and safety in the treatment of mild cases of COVID-19. Front. Med. 10, 1143485 (2023).
doi: 10.3389/fmed.2023.1143485
Gao, Y. et al. Antiviral effect of azvudine and nirmatrelvir-ritonavir among hospitalized patients with COVID-19. J. Infect. 86, e158–e160 (2023).
doi: 10.1016/j.jinf.2023.03.023 pubmed: 37003523 pmcid: 10062713
Petrakis, V., Rafailidis, P., Trypsianis, G., Papazoglou, D. & Panagopoulos, P. The antiviral effect of nirmatrelvir/ritonavir during COVID-19 pandemic real-world data. Viruses 15, 976 (2023).
doi: 10.3390/v15040976 pubmed: 37112956 pmcid: 10144059
Gao, Y., Liu, M., Li, Z., Xu, J., Zhang, J. & Tian, J. Molnupiravir for treatment of adults with mild or moderate COVID-19: A systematic review and meta-analysis of randomized controlled trials. Clin. Microbiol. Infect., (2023).
Zhou, Z. et al. Clinical characteristics of older and younger patients infected with SARS-CoV-2. Aging (Albany NY) 12, 11296–11305 (2020).
doi: 10.18632/aging.103535 pubmed: 32575073
Vujcic, I. Outcomes of COVID-19 among patients with liver disease. World J. Gastroenterol. 29, 815–824 (2023).
doi: 10.3748/wjg.v29.i5.815 pubmed: 36816621 pmcid: 9932431
Przekop, D., Gruszewska, E. & Chrostek, L. Liver function in COVID-19 infection. World J. Hepatol. 13, 1909–1918 (2021).
doi: 10.4254/wjh.v13.i12.1909 pubmed: 35069997 pmcid: 8727219
Yu, D. et al. Liver injury in COVID-19: Clinical features and treatment management. Virol. J. 18, 121 (2021).
doi: 10.1186/s12985-021-01593-1 pubmed: 34108015 pmcid: 8188532
Grandvuillemin, A., Rocher, F., Valnet-Rabier, M. B., Drici, M. D. & Dautriche, A. French Pharmacovigilance, N. Pharmacovigilance follow-up of patients in the context of the COVID-19 pandemic. Therapie, (2023).
Lory, P. et al. Safety profile of the lopinavir/ritonavir combination before and during the SARS-CoV-2 pandemic. Therapie 78, 419–425 (2022).
doi: 10.1016/j.therap.2022.10.066 pubmed: 36376122
Casalini, G., Giacomelli, A. & Antinori, S. Liver tests abnormalities with licensed antiviral drugs for COVID-19: A narrative review. Expert Opin. Drug Saf. 21, 1483–1494 (2022).
doi: 10.1080/14740338.2022.2160446 pubmed: 36597859
Painter, W. P. et al. Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2. Antimicrob. Agents Chemother. 65, 10–1128 (2021).
doi: 10.1128/AAC.02428-20
Kale, A., Shelke, V., Dagar, N., Anders, H. J. & Gaikwad, A. B. How to use COVID-19 antiviral drugs in patients with chronic kidney disease. Front. Pharmacol. 14, 1053814 (2023).
doi: 10.3389/fphar.2023.1053814 pubmed: 36843922 pmcid: 9947246
Izzedine, H., Jhaveri, K. D. & Perazella, M. A. COVID-19 therapeutic options for patients with kidney disease. Kidney Int. 97, 1297–1298 (2020).
doi: 10.1016/j.kint.2020.03.015 pubmed: 32317113 pmcid: 7271263
Sun, Y. et al. Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: A retrospective cohort study. ClinicalMedicine 59, e101981 (2023).
doi: 10.1016/j.eclinm.2023.101981
Parums, D. V. Editorial: Rebound COVID-19 and cessation of antiviral treatment for SARS-CoV-2 with paxlovid and molnupiravir. Med. Sci. Monit. 28, e938532 (2022).
doi: 10.12659/MSM.938532 pubmed: 36181334 pmcid: 9536144
Anderson, A. S., Caubel, P., Rusnak, J. M. & Investigators, E.-H.T. Nirmatrelvir–ritonavir and viral load rebound in Covid-19. N. Engl. J. Med. 387, 1047–1049 (2022).
doi: 10.1056/NEJMc2205944 pubmed: 36069818
Charness, M. E. et al. Rebound of SARS-CoV-2 infection after nirmatrelvir-ritonavir treatment. N. Engl. J. Med. 387, 1045–1047 (2022).
doi: 10.1056/NEJMc2206449 pubmed: 36069968
Rubin, R. From positive to negative to positive again-the mystery of why COVID-19 rebounds in some patients who take paxlovid. JAMA 327, 2380–2382 (2022).
doi: 10.1001/jama.2022.9925 pubmed: 35675094
Zhou, Z. G. et al. Low-dose corticosteroid combined with immunoglobulin reverses deterioration in severe cases with COVID-19. Signal Transduct. Target. Ther. 5, 276 (2020).
doi: 10.1038/s41392-020-00407-0 pubmed: 33235253 pmcid: 7683873

Auteurs

Mei-Ping Chen (MP)

Department of Infectious Disease, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (The First Hospital of Changsha), Changsha, 410000, People's Republic of China.

Di-Xuan Jiang (DX)

Department of Respiratory and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (The First Hospital of Changsha), Changsha, 410000, People's Republic of China.

Jia-Xi Rang (JX)

Department of Nurse, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (The First Hospital of Changsha), Changsha, 410000, People's Republic of China.

Hai-Bo Zhuo (HB)

Department of Respiratory and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (The First Hospital of Changsha), Changsha, 410000, People's Republic of China.

Zhi-Guo Zhou (ZG)

Department of Respiratory and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (The First Hospital of Changsha), Changsha, 410000, People's Republic of China. zhouzhiguo1217@163.com.

Classifications MeSH