Volume 29, Issue 2 (June 2025)                   Physiol Pharmacol 2025, 29(2): 111-122 | Back to browse issues page


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Maghbooli Z, Kasaeian A, Fattahi M R, Varzandi T, Hamtaeigashi S, Mohammadnabi S et al . Enhancing Clinical Outcomes and Survival in Hospitalized Multiple Sclerosis Patients with COVID-19: Challenges of Antiviral Therapy. Physiol Pharmacol 2025; 29 (2) :111-122
URL: http://ppj.phypha.ir/article-1-2433-en.html
Abstract:   (594 Views)
Introduction: This study aimed to evaluate the efficacy and safety concerns of remdesivir and type 1 interferons on the clinical outcomes of hospitalized multiple sclerosis patients with COVID-19.
Methods: Using electronic health records systems; this is a cross-sectional study of two years of hospital admissions in terms of COVID-19 in Iran from March 2019 to August 2021. The severities of COVID-19 outcomes were ICU admission, hospitalization days, and 30-day survival rates.
Results: A total of 993 hospitalized multiple sclerosis patients with a confirmed diagnosis of COVID-19 based on PCR testing were recorded in the electronic health systems. Nearly half of these patients (50.3%) had received treatment with an anti-CD20 agent (rituximab or ocrelizumab) at the hospital admission. This group exhibited higher mortality rates, increased need for ICU admission, and longer hospitalization (p<0.05).
There was a significant association between taking interferon-β1 alone (adjusted IRR=1.21, 95% CI 1.32 to 1.42) or in combination with remdesivir (adjusted IRR=1.30, 95% CI 1.18 to 1.5042) and longer hospitalization.
There were no significant associations between antiviral treatment (remdesivir alone, interferon-β1- β1 alone, and interferon-β1plus remdesivir) and ICU admission (p>0.2), the in-hospital mortality rate (p>0.2), or 30-day survival rate (p>0.2). The results were similar in patients who did or did not receive anti-CD20 agents. These results were consistent among patients regardless of whether they received anti-CD20 agents.
Conclusion: Our data suggest that remdesivir, interferon-β1, or a combination of both does not benefit hospitalized MS patients with COVID-19.
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References
1. Baldi F, Dentone C, Mikulska M, Fenoglio D, Mirabella M, Magnè F, et al. Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19. Frontiers in Medicine 2022; 9: 1062450. [DOI:10.3389/fmed.2022.1062450]
2. Bellucci G, Albanese A, Rizzi C, Rinaldi V, Salvetti M, Ristori G. The value of Interferon β in multiple sclerosis and novel opportunities for its anti-viral activity: a narrative literature review. Frontiers in Immunology 2023; 14: 1161849. [DOI:10.3389/fimmu.2023.1161849]
3. Chisari C G, Sgarlata E, Arena S, Toscano S, Luca M, Patti F. Rituximab for the treatment of multiple sclerosis: a review. Journal of Neurology 2022; 269: 159-183. [DOI:10.1007/s00415-020-10362-z]
4. Cragg M S, Walshe C A, Ivanov A O, Glennie M J. The biology of CD20 and its potential as a target for mAb therapy. Current directions in autoimmunity 2005; 8: 140-174. [DOI:10.1159/000082102]
5. D’Abramo A, Vita S, Maffongelli G, Mariano A, Agrati C, Castilletti C, et al. Prolonged and severe SARS-CoV-2 infection in patients under B-cell-depleting drug successfully treated: A tailored approach. Int J Infect Dis 2021; 107: 247-250. [DOI:10.1016/j.ijid.2021.04.068]
6. Davoudi-Monfared E, Rahmani H, Khalili H, Hajiabdolbaghi M, Salehi M, Abbasian L, et al. A Randomized clinical trial of the efficacy and safety of interferon β-1a in treatment of severe Covid-19. Antimicrob Agents Chemother 2020; 64. [DOI:10.1128/AAC.01061-20]
7. De Wit E, Van Doremalen N, Falzarano D, Munster V J. SARS and MERS: recent insights into emerging coronaviruses. Nature reviews microbiology 2016; 14: 523-534. [DOI:10.1038/nrmicro.2016.81]
8. Furlan A, Forner G, Cipriani L, Vian E, Rigoli R, Gherlinzoni F, et al. Covid-19 in B cell-depleted patients after rituximab: A diagnostic and therapeutic challenge. Frontiers in Immunology 2021; 12: 763412. [DOI:10.3389/fimmu.2021.763412]
9. Haddad F, Dokmak G, Karaman R. A Comprehensive review on the efficacy of several pharmacologic agents for the treatment of Covid-19. Life 2022; 12: 1758. [DOI:10.3390/life12111758]
10. Hartinger J M, Kratky V, Hruskova Z, Slanar O, Tesar V. Implications of rituximab pharmacokinetic and pharmacodynamic alterations in various immune-mediated glomerulopathies and potential anti-CD20 therapy alternatives. Frontiers in Immunology 2022; 13: 1024068. [DOI:10.3389/fimmu.2022.1024068]
11. Hashemi-Meshkini A, Koochak R, Nikfar S, Rezaei-Darzi E, Yaghoubifard S. Evaluation of Covid-19 treatments in iran in comparison with local therapeutic recommendations: A population-level study on utilization and costs of prescription drugs. Journal of Research in Pharmacy Practice 2022; 11: 1-7. [DOI:10.4103/jrpp.jrpp_6_22]
12. Hawker K, O’Connor P, Freedman M S, Calabresi P A, Antel J, Simon J, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Annals of Neurology 2009; 66: 460-471. [DOI:10.1002/ana.21867]
13. Hollen C, Bernard J. Multiple sclerosis management during the Covid-19 pandemic. Current Neurology and Neuroscience Reports 2022; 22: 537-543. [DOI:10.1007/s11910-022-01211-9]
14. https://www.covid19treatmentguidelines.nih.gov/. Covid-19 treatment guidelines panel. coronavirus disease 2019 (Covid-19) treatment guidelines. National Institutes of Health.
15. Hueso T, Pouderoux C, Péré H, Beaumont A L, Raillon L A, Ader F, et al. Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19. Blood 2020; 136: 2290-2295. [DOI:10.1182/blood.2020008423]
16. Hughes R, Whitley L, Fitovski K, Schneble H-M, Muros E, Sauter A, et al. COVID-19 in ocrelizumab-treated people with multiple sclerosis. Multiple Sclerosis and Related Disorders 2021; 49: 102725. [DOI:10.1016/j.msard.2020.102725]
17. Jakimovski D, Kolb C, Ramanathan M, Zivadinov R, Weinstock-Guttman B. Interferon β for multiple sclerosis. Cold Spring Harbor Perspectives in Medicine 2018; 8. [DOI:10.1101/cshperspect.a032003]
18. Januel E, Hajage D, Labauge P, Maillart E, De Sèze J, Zephir H, et al. Association between anti-CD20 therapies and Covid-19 severity among patients with relapsing-remitting and progressive multiple sclerosis. JAMA Network Open 2023; 6: e2319766-e2319766. [DOI:10.1001/jamanetworkopen.2023.19766]
19. Jelcic I, Al Nimer F, Wang J, Lentsch V, Planas R, Jelcic I, et al. Memory B cells activate brain-homing, autoreactive CD4(+) T cells in multiple sclerosis. Cell 2018; 175: 85-100. [DOI:10.1016/j.cell.2018.08.011]
20. Kado R, Sanders G, McCune W J. Suppression of normal immune responses after treatment with rituximab. Current Opinion in Rheumatology 2016; 28: 251-258. [DOI:10.1097/BOR.0000000000000272]
21. Kalil A C, Mehta A K, Patterson T F, Erdmann N, Gomez C A, Jain M K, et al. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. The Lancet Respiratory Medicine 2021; 9: 1365-1376.
22. Kintrilis N, Gkinos C P, Galinos I. Prolonged Covid-19 in a multiple sclerosis patient treated with rituximab. Cureus 2022; 14: e32523. [DOI:10.7759/cureus.32523]
23. Lassmann H. Pathogenic mechanisms associated with different clinical courses of multiple sclerosis. Frontiers in Immunology 2018; 9: 3116. [DOI:10.3389/fimmu.2018.03116]
24. Lisak R P, Benjamins J A, Nedelkoska L, Barger J L, Ragheb S, Fan B, et al. Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro. Journal of Neuroimmunology 2012; 246: 85-95. [DOI:10.1016/j.jneuroim.2012.02.015]
25. Maghbooli Z, Hosseinpour H, Fattahi M R, Varzandi T, Hamtaeigashi S, Mohammad-Nabi S, et al. Association between disease-modifying therapies and adverse clinical outcomes in multiple sclerosis patients with Covid-19 infection. Multiple Sclerosis and Related Disorders 2022; 67: 104067. [DOI:10.1016/j.msard.2022.104067]
26. Mary A, Hénaut L, Macq P Y, Badoux L, Cappe A, Porée T, et al. Rationale for Covid-19 treatment by nebulized interferon-β-1b-literature review and personal preliminary experience. Frontiers in Pharmacology 2020; 11: 592543. [DOI:10.3389/fphar.2020.592543]
27. McLaughlin P, Grillo-López A J, Link B K, Levy R, Czuczman M S, Williams M E, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. Journal of Clinical Oncology 1998; 16: 2825-2833. [DOI:10.1200/JCO.1998.16.8.2825]
28. Mehta P, Porter J C, Chambers R C, Isenberg D A, Reddy V. B-cell depletion with rituximab in the COVID-19 pandemic: where do we stand? Lancet Rheumatol 2020; 2: e589-e590. [DOI:10.1016/S2665-9913(20)30270-8]
29. Okoli G N, Reddy V K, Lam O L, Askin N, Rabbani R. Update on efficacy of the approved remdesivir regimen for treatment of Covid-19: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials. Current Medical Research and Opinion 2024; 40: 1277-1287. [DOI:10.1080/03007995.2024.2366443]
30. Pan H, Peto R, Henao-Restrepo A M, Preziosi M P, Sathiyamoorthy V, Abdool Karim Q, et al. Repurposed antiviral drugs for Covid-19 - interim WHO solidarity trial results. The New England Journal of Medicine 2021; 384: 497-511. [DOI:10.1056/NEJMoa2023184]
31. Schreiber G. The Role of type I interferons in the pathogenesis and treatment of Covid-19. Frontiers in Immunology 2020; 11: 595739. [DOI:10.3389/fimmu.2020.595739]
32. Spinner C D, Gottlieb R L, Criner G J, Arribas López J R, Cattelan A M, Soriano Viladomiu A, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate Covid-19: A randomized clinical trial. Jama 2020; 324: 1048-1057. [DOI:10.1001/jama.2020.16349]
33. van der Kolk L E, Baars J W, Prins M H, van Oers M H. Rituximab treatment results in impaired secondary humoral immune responsiveness. Blood 2002; 100: 2257-2259. [DOI:10.1182/blood.V100.6.2257.h81802002257_2257_2259]

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