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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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General Review Article

Drugs Used in the Treatment of Multiple Sclerosis During COVID-19 Pandemic: A Critical Viewpoint

Author(s): Marika Alborghetti*, Gianmarco Bellucci*, Antonietta Gentile*, Chiara Calderoni, Ferdinando Nicoletti, Ruggero Capra, Marco Salvetti and Diego Centonze*

Volume 20, Issue 1, 2022

Page: [107 - 125] Pages: 19

DOI: 10.2174/1570159X19666210330094017

Price: $65

Abstract

Since COVID-19 has emerged as a word public health problem, attention has been focused on how immune-suppressive drugs used for the treatment of autoimmune disorders influence the risk for SARS-CoV-2 infection and the development of acute respiratory distress syndrome (ARDS). Here, we discuss the disease-modifying agents approved for the treatment of multiple sclerosis (MS) within this context. Interferon (IFN)-β1a and -1b, which display antiviral activity, could be protective in the early stage of COVID-19 infection, although SARS-CoV-2 may have developed resistance to IFNs. However, in the hyperinflammation stage, IFNs may become detrimental by facilitating macrophage invasion in the lung and other organs. Glatiramer acetate and its analogues should not interfere with the development of COVID-19 and may be considered safe. Teriflunomide, a first-line oral drug used in the treatment of relapsing-remitting MS (RRMS), may display antiviral activity by depleting cellular nucleotides necessary for viral replication. The other first-line drug, dimethyl fumarate, may afford protection against SARS-CoV-2 by activating the Nrf-2 pathway and reinforcing the cellular defenses against oxidative stress. Concern has been raised regarding the use of second-line treatments for MS during the COVID-19 pandemic. However, this concern is not always justified. For example, fingolimod might be highly beneficial during the hyperinflammatory stage of COVID-19 for a number of mechanisms, including the reinforcement of the endothelial barrier. Caution is suggested for the use of natalizumab, cladribine, alemtuzumab, and ocrelizumab, although MS disease recurrence after discontinuation of these drugs may overcome a potential risk for COVID-19 infection.

Keywords: Disease-modifying therapy, multiple sclerosis, COVID-19 pandemic, Sars-Cov-2, immunomodulation, neuroprotection, cytokine storm, risk-benefit ratio

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[1]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[2]
Hu, B.; Guo, H.; Zhou, P.; Shi, Z.L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol., 2020, 19(3), 1-14.
[PMID: 33024307]
[3]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[4]
Hikmet, F.; Méar, L.; Edvinsson, Å.; Micke, P.; Uhlén, M.; Lindskog, C. The protein expression profile of ACE2 in human tissues. Mol. Syst. Biol., 2020, 16(7)e9610
[http://dx.doi.org/10.15252/msb.20209610] [PMID: 32715618]
[5]
Cantuti-Castelvetri, L.; Ojha, R.; Pedro, L.D.; Djannatian, M.; Franz, J.; Kuivanen, S.; van der Meer, F.; Kallio, K.; Kaya, T.; Anastasina, M.; Smura, T.; Levanov, L.; Szirovicza, L.; Tobi, A.; Kallio-Kokko, H.; Österlund, P.; Joensuu, M.; Meunier, F.A.; Butcher, S.J.; Winkler, M.S.; Mollenhauer, B.; Helenius, A.; Gokce, O.; Teesalu, T.; Hepojoki, J.; Vapalahti, O.; Stadelmann, C.; Balistreri, G.; Simons, M. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science, 2020, 370(6518), 856-860.
[http://dx.doi.org/10.1126/science.abd2985] [PMID: 33082293]
[6]
Daly, J.L.; Simonetti, B.; Klein, K.; Chen, K.E.; Williamson, M.K.; Antón-Plágaro, C.; Shoemark, D.K.; Simón-Gracia, L.; Bauer, M.; Hollandi, R.; Greber, U.F.; Horvath, P.; Sessions, R.B.; Helenius, A.; Hiscox, J.A.; Teesalu, T.; Matthews, D.A.; Davidson, A.D.; Collins, B.M.; Cullen, P.J.; Yamauchi, Y. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science, 2020, 370(6518), 861-865.
[http://dx.doi.org/10.1126/science.abd3072] [PMID: 33082294]
[7]
Siddiqi, H.K.; Mehra, M.R. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J. Heart Lung Transplant., 2020, 39(5), 405-407.
[http://dx.doi.org/10.1016/j.healun.2020.03.012] [PMID: 32362390]
[8]
Harrison, AG; Lin, T. Wang, P Mechanisms of sars-cov-2 transmission and pathogenesis. Trends Immunol., 2020, 41(12), 1100-1115.
[9]
Giamarellos-Bourboulis, E.J.; Netea, M.G.; Rovina, N.; Akinosoglou, K.; Antoniadou, A.; Antonakos, N.; Damoraki, G.; Gkavogianni, T.; Adami, M.E.; Katsaounou, P.; Ntaganou, M.; Kyriakopoulou, M.; Dimopoulos, G.; Koutsodimitropoulos, I.; Velissaris, D.; Koufargyris, P.; Karageorgos, A.; Katrini, K.; Lekakis, V.; Lupse, M.; Kotsaki, A.; Renieris, G.; Theodoulou, D.; Panou, V.; Koukaki, E.; Koulouris, N.; Gogos, C.; Koutsoukou, A. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe, 2020, 27(6), 992-1000.e3.
[http://dx.doi.org/10.1016/j.chom.2020.04.009] [PMID: 32320677]
[10]
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, 2020, 324(8), 782-793.
[http://dx.doi.org/10.1001/jama.2020.12839] [PMID: 32648899]
[11]
Williamson, E.J.; Walker, A.J.; Bhaskaran, K.; Bacon, S.; Bates, C.; Morton, C.E.; Curtis, H.J.; Mehrkar, A.; Evans, D.; Inglesby, P.; Cockburn, J.; McDonald, H.I.; MacKenna, B.; Tomlinson, L.; Douglas, I.J.; Rentsch, C.T.; Mathur, R.; Wong, A.Y.S.; Grieve, R.; Harrison, D.; Forbes, H.; Schultze, A.; Croker, R.; Parry, J.; Hester, F.; Harper, S.; Perera, R.; Evans, S.J.W.; Smeeth, L.; Goldacre, B. Factors associated with COVID-19-related death using opensafely. Nature, 2020, 584(7821), 430-436.
[http://dx.doi.org/10.1038/s41586-020-2521-4] [PMID: 32640463]
[12]
Luna, G.; Alping, P.; Burman, J.; Fink, K.; Fogdell-Hahn, A.; Gunnarsson, M.; Hillert, J.; Langer-Gould, A.; Lycke, J.; Nilsson, P.; Salzer, J.; Svenningsson, A.; Vrethem, M.; Olsson, T.; Piehl, F.; Frisell, T. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol., 2020, 77(2), 184-191.
[http://dx.doi.org/10.1001/jamaneurol.2019.3365] [PMID: 31589278]
[13]
Bowen, J.D.; Brink, J.; Brown, T.R.; Lucassen, E.B.; Smoot, K.; Wundes, A.; Repovic, P. COVID-19 in MS: Initial observations from the Pacific Northwest. Neurol. Neuroimmunol. Neuroinflamm., 2020, 7(5)e783
[http://dx.doi.org/10.1212/NXI.0000000000000783] [PMID: 32457226]
[14]
Fan, M.; Qiu, W.; Bu, B.; Xu, Y.; Yang, H.; Huang, D.; Lau, A.Y.; Guo, J.; Zhang, M.N.; Zhang, X.; Yang, C.S.; Chen, J.; Zheng, P.; Liu, Q.; Zhang, C.; Shi, F.D. Risk of COVID-19 infection in MS and neuromyelitis optica spectrum disorders. Neurol. Neuroimmunol. Neuroinflamm., 2020, 7(5)e787
[http://dx.doi.org/10.1212/NXI.0000000000000787] [PMID: 32503092]
[15]
Louapre, C.; Collongues, N.; Stankoff, B.; Giannesini, C.; Papeix, C.; Bensa, C.; Deschamps, R.; Créange, A.; Wahab, A.; Pelletier, J.; Heinzlef, O.; Labauge, P.; Guilloton, L.; Ahle, G.; Goudot, M.; Bigaut, K.; Laplaud, D.A.; Vukusic, S.; Lubetzki, C.; De Sèze, J.; Derouiche, F.; Tourbah, A.; Mathey, G.; Théaudin, M.; Sellal, F.; Dugay, M.H.; Zéphir, H.; Vermersch, P.; Durand-Dubief, F.; Françoise, R.; Androdias-Condemine, G.; Pique, J.; Codjia, P.; Tilikete, C.; Marcaud, V.; Lebrun-Frenay, C.; Cohen, M.; Ungureanu, A.; Maillart, E.; Beigneux, Y.; Roux, T.; Corvol, J.C.; Bordet, A.; Mathieu, Y.; Le Breton, F.; Boulos, D.D.; Gout, O.; Guéguen, A.; Moulignier, A.; Boudot, M.; Chardain, A.; Coulette, S.; Manchon, E.; Ayache, S.S.; Moreau, T.; Garcia, P.Y.; Kumaran, D.; Castelnovo, G.; Thouvenot, E.; Taithe, F.; Poupart, J.; Kwiatkowski, A.; Defer, G.; Derache, N.; Branger, P.; Biotti, D.; Ciron, J.; Clerc, C.; Vaillant, M.; Magy, L.; Montcuquet, A.; Kerschen, P.; Coustans, M.; Guennoc, A.M.; Brochet, B.; Ouallet, J.C.; Ruet, A.; Dulau, C.; Wiertlewski, S.; Berger, E.; Buch, D.; Bourre, B.; Pallix-Guiot, M.; Maurousset, A.; Audoin, B.; Rico, A.; Maarouf, A.; Edan, G.; Papassin, J.; Videt, D. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol., 2020, 77(9), 1079-1088.
[http://dx.doi.org/10.1001/jamaneurol.2020.2581] [PMID: 32589189]
[16]
Sepúlveda, M.; Llufriu, S.; Martínez-Hernández, E.; Català, M.; Artola, M.; Hernando, A.; Montejo, C.; Pulido-Valdeolivas, I.; Martínez-Heras, E.; Guasp, M.; Solana, E.; Llansó, L.; Escudero, D.; Aldea, M.; Prats, C.; Graus, F.; Blanco, Y.; Saiz, A. Incidence and impact of COVID-19 in MS: A survey from a barcelona MS Unit. Neurol. Neuroimmunol. Neuroinflamm., 2021, 8(2)e954
[http://dx.doi.org/10.1212/NXI.0000000000000954] [PMID: 33504634]
[17]
Levin, S.N.; Venkatesh, S.; Nelson, K.E.; Li, Y.; Aguerre, I.; Zhu, W.; Masown, K.; Rimmer, K.T.; Diaconu, C.I.; Onomichi, K.B.; Leavitt, V.M.; Levine, L.L.; Strauss-Farber, R.; Vargas, W.S.; Banwell, B.; Bar-Or, A.; Berger, J.R.; Goodman, A.D.; Longbrake, E.E.; Oh, J.; Weinstock-Guttman, B.; Thakur, K.T.; Edwards, K.R.; Riley, C.S.; Xia, Z.; De Jager, P.L. Multiple Sclerosis Resilience to COVID-19 (MSReCOV) Collaborative. Manifestations and impact of the COVID-19 pandemic in neuroinflammatory diseases. Ann. Clin. Transl. Neurol., 2021, 8(4), 918-928.
[http://dx.doi.org/10.1002/acn3.51314]
[18]
Mallucci, G.; Zito, A.; Baldanti, F.; Gastaldi, M.; Fabbro, B.D.; Franciotta, D.; Bergamaschi, R. Safety of disease-modifying treatments in SARS-CoV-2 antibody-positive multiple sclerosis patients. Mult. Scler. Relat. Disord., 2021, 49102754
[http://dx.doi.org/10.1016/j.msard.2021.102754] [PMID: 33609958]
[19]
Sormani, M.P. An Italian programme for COVID-19 infection in multiple sclerosis. Lancet Neurol., 2020, 19(6), 481-482.
[http://dx.doi.org/10.1016/S1474-4422(20)30147-2] [PMID: 32359409]
[20]
Parrotta, E.; Kister, I.; Charvet, L.; Sammarco, C.; Saha, V.; Charlson, R.E.; Howard, J.; Gutman, J.M.; Gottesman, M.; Abou-Fayssal, N.; Wolintz, R.; Keilson, M.; Fernandez-Carbonell, C.; Krupp, L.B.; Zhovtis Ryerson, L. COVID-19 outcomes in MS: observational study of early experience from NYU multiple sclerosis comprehensive care center. Neurol. Neuroimmunol. Neuroinflamm., 2020, 7(5)e835
[http://dx.doi.org/10.1212/NXI.0000000000000835] [PMID: 32646885]
[21]
Sormani, M.P.; De Rossi, N.; Schiavetti, I.; Carmisciano, L.; Cordioli, C.; Moiola, L.; Radaelli, M.; Immovilli, P.; Capobianco, M.; Trojano, M.; Zaratin, P.; Tedeschi, G.; Comi, G.; Battaglia, M.A.; Patti, F.; Salvetti, M. Disease-modifying therapies and coronavirus Disease 2019 severity in multiple sclerosis. Ann. Neurol., 2021, 89(4), 780-789.
[http://dx.doi.org/10.1002/ana.26028] [PMID: 33480077]
[22]
Zhang, Y.; Staker, E.; Cutter, G.; Krieger, S.; Miller, A.E. Perceptions of risk and adherence to care in MS patients during the COVID-19 pandemic: A cross-sectional study. Mult. Scler. Relat. Disord., 2021, 50102856
[http://dx.doi.org/10.1016/j.msard.2021.102856] [PMID: 33662858]
[23]
Bodro, M.; Compta, Y.; Sánchez-Valle, R. Presentations and mechanisms of CNS disorders related to COVID-19. Neurol. Neuroimmunol. Neuroinflamm., 2020, 8(1)e923
[http://dx.doi.org/10.1212/NXI.0000000000000923] [PMID: 33310765]
[24]
Meinhardt, J.; Radke, J.; Dittmayer, C.; Franz, J.; Thomas, C.; Mothes, R.; Laue, M.; Schneider, J.; Brünink, S.; Greuel, S.; Lehmann, M.; Hassan, O.; Aschman, T.; Schumann, E.; Chua, R.L.; Conrad, C.; Eils, R.; Stenzel, W.; Windgassen, M.; Rößler, L.; Goebel, H.H.; Gelderblom, H.R.; Martin, H.; Nitsche, A.; Schulz-Schaeffer, W.J.; Hakroush, S.; Winkler, M.S.; Tampe, B.; Scheibe, F.; Körtvélyessy, P.; Reinhold, D.; Siegmund, B.; Kühl, A.A.; Elezkurtaj, S.; Horst, D.; Oesterhelweg, L.; Tsokos, M.; Ingold-Heppner, B.; Stadelmann, C.; Drosten, C.; Corman, V.M.; Radbruch, H.; Heppner, F.L. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci., 2021, 24(2), 168-175.
[http://dx.doi.org/10.1038/s41593-020-00758-5] [PMID: 33257876]
[25]
Fuchs, V.; Kutza, M.; Wischnewski, S.; Deigendesch, N.; Lutz, L.; Kulsvehagen, L.; Ricken, G.; Kappos, L.; Tzankov, A.; Hametner, S.; Frank, S.; Schirmer, L.; Pröbstel, A.K. Presence of SARS-CoV-2 transcripts in the choroid plexus of MS and Non-MS patients With COVID-19. Neurol. Neuroimmunol. Neuroinflamm., 2021, 8(2)e957
[http://dx.doi.org/10.1212/NXI.0000000000000957] [PMID: 33504636]
[26]
Liotta, E.M.; Batra, A.; Clark, J.R.; Shlobin, N.A.; Hoffman, S.C.; Orban, Z.S.; Koralnik, I.J. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann. Clin. Transl. Neurol., 2020, 7(11), 2221-2230.
[http://dx.doi.org/10.1002/acn3.51210] [PMID: 33016619]
[27]
Schneider, W.M.; Chevillotte, M.D.; Rice, C.M. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol., 2014, 32, 513-545.
[http://dx.doi.org/10.1146/annurev-immunol-032713-120231] [PMID: 24555472]
[28]
Severa, M.; Farina, C.; Salvetti, M.; Coccia, E.M. Three Decades of Interferon-β in multiple sclerosis: can we repurpose this information for the management of SARS-CoV2 Infection? Front. Immunol., 2020, 11, 1459.
[http://dx.doi.org/10.3389/fimmu.2020.01459] [PMID: 32655578]
[29]
Schreiber, G. The role of type I Interferons in the pathogenesis and treatment of COVID-19. Front. Immunol., 2020, 11595739
[http://dx.doi.org/10.3389/fimmu.2020.595739] [PMID: 33117408]
[30]
Clementi, N.; Ferrarese, R.; Criscuolo, E.; Diotti, R.A.; Castelli, M.; Scagnolari, C.; Burioni, R.; Antonelli, G.; Clementi, M.; Mancini, N. Interferon-β-1a inhibition of severe acute respiratory syndrome-coronavirus 2 in vitro when administered after virus infection. J. Infect. Dis., 2020, 222(5), 722-725.
[http://dx.doi.org/10.1093/infdis/jiaa350] [PMID: 32559285]
[31]
Lokugamage, K.G.; Hage, A.; de Vries, M.; Valero-Jimenez, A.M.; Schindewolf, C.; Dittmann, M.; Rajsbaum, R.; Menachery, V.D.; Type, I. Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. J. Virol., 2020, 94(23), e01410-e01420.
[http://dx.doi.org/10.1128/JVI.01410-20] [PMID: 32938761]
[32]
Lei, X.; Dong, X.; Ma, R.; Wang, W.; Xiao, X.; Tian, Z.; Wang, C.; Wang, Y.; Li, L.; Ren, L.; Guo, F.; Zhao, Z.; Zhou, Z.; Xiang, Z.; Wang, J. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun., 2020, 11(1), 3810.
[http://dx.doi.org/10.1038/s41467-020-17665-9] [PMID: 32733001]
[33]
Jamilloux, Y.; Henry, T.; Belot, A.; Viel, S.; Fauter, M.; El Jammal, T.; Walzer, T.; François, B.; Sève, P. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun. Rev., 2020, 19(7)102567
[http://dx.doi.org/10.1016/j.autrev.2020.102567] [PMID: 32376392]
[34]
Channappanavar, R.; Fehr, A.R.; Vijay, R.; Mack, M.; Zhao, J.; Meyerholz, D.K.; Perlman, S. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe, 2016, 19(2), 181-193.
[http://dx.doi.org/10.1016/j.chom.2016.01.007] [PMID: 26867177]
[35]
Acharya, D.; Liu, G.; Gack, M.U. Dysregulation of type I interferon responses in COVID-19. Nat. Rev. Immunol., 2020, 20(7), 397-398.
[http://dx.doi.org/10.1038/s41577-020-0346-x] [PMID: 32457522]
[36]
Hadjadj, J.; Yatim, N.; Barnabei, L.; Corneau, A.; Boussier, J.; Smith, N.; Péré, H.; Charbit, B.; Bondet, V.; Chenevier-Gobeaux, C.; Breillat, P.; Carlier, N.; Gauzit, R.; Morbieu, C.; Pène, F.; Marin, N.; Roche, N.; Szwebel, T.A.; Merkling, S.H.; Treluyer, J.M.; Veyer, D.; Mouthon, L.; Blanc, C.; Tharaux, P.L.; Rozenberg, F.; Fischer, A.; Duffy, D.; Rieux-Laucat, F.; Kernéis, S.; Terrier, B. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science, 2020, 369(6504), 718-724.
[http://dx.doi.org/10.1126/science.abc6027] [PMID: 32661059]
[37]
Xu, G.; Qi, F.; Li, H.; Yang, Q.; Wang, H.; Wang, X.; Liu, X.; Zhao, J.; Liao, X.; Liu, Y.; Liu, L.; Zhang, S.; Zhang, Z. The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing. Cell Discov., 2020, 6, 73.
[http://dx.doi.org/10.1038/s41421-020-00225-2] [PMID: 33101705]
[38]
Bastard, P.; Rosen, L.B.; Zhang, Q.; Michailidis, E.; Hoffmann, H.H.; Zhang, Y.; Dorgham, K.; Philippot, Q.; Rosain, J.; Béziat, V.; Manry, J.; Shaw, E.; Haljasmägi, L.; Peterson, P.; Lorenzo, L.; Bizien, L.; Trouillet-Assant, S.; Dobbs, K.; de Jesus, A.A.; Belot, A.; Kallaste, A.; Catherinot, E.; Tandjaoui-Lambiotte, Y.; Le Pen, J.; Kerner, G.; Bigio, B.; Seeleuthner, Y.; Yang, R.; Bolze, A.; Spaan, A.N.; Delmonte, O.M.; Abers, M.S.; Aiuti, A.; Casari, G.; Lampasona, V.; Piemonti, L.; Ciceri, F.; Bilguvar, K.; Lifton, R.P.; Vasse, M.; Smadja, D.M.; Migaud, M.; Hadjadj, J.; Terrier, B.; Duffy, D.; Quintana-Murci, L.; van de Beek, D.; Roussel, L.; Vinh, D.C.; Tangye, S.G.; Haerynck, F.; Dalmau, D.; Martinez-Picado, J.; Brodin, P.; Nussenzweig, M.C.; Boisson-Dupuis, S.; Rodríguez-Gallego, C.; Vogt, G.; Mogensen, T.H.; Oler, A.J.; Gu, J.; Burbelo, P.D.; Cohen, J.I.; Biondi, A.; Bettini, L.R.; D’Angio, M.; Bonfanti, P.; Rossignol, P.; Mayaux, J.; Rieux-Laucat, F.; Husebye, E.S.; Fusco, F.; Ursini, M.V.; Imberti, L.; Sottini, A.; Paghera, S.; Quiros-Roldan, E.; Rossi, C.; Castagnoli, R.; Montagna, D.; Licari, A.; Marseglia, G.L.; Duval, X.; Ghosn, J.; Tsang, J.S.; Goldbach-Mansky, R.; Kisand, K.; Lionakis, M.S.; Puel, A.; Zhang, S.Y.; Holland, S.M.; Gorochov, G.; Jouanguy, E.; Rice, C.M.; Cobat, A.; Notarangelo, L.D.; Abel, L.; Su, H.C.; Casanova, J.L. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science, 2020, 370(6515)eabd4585
[http://dx.doi.org/10.1126/science.abd4585] [PMID: 32972996]
[39]
Zhang, Q.; Bastard, P.; Liu, Z.; Le Pen, J.; Moncada-Velez, M.; Chen, J.; Ogishi, M.; Sabli, I.K.D.; Hodeib, S.; Korol, C.; Rosain, J.; Bilguvar, K.; Ye, J.; Bolze, A.; Bigio, B.; Yang, R.; Arias, A.A.; Zhou, Q.; Zhang, Y.; Onodi, F.; Korniotis, S.; Karpf, L.; Philippot, Q.; Chbihi, M.; Bonnet-Madin, L.; Dorgham, K.; Smith, N.; Schneider, W.M.; Razooky, B.S.; Hoffmann, H.H.; Michailidis, E.; Moens, L.; Han, J.E.; Lorenzo, L.; Bizien, L.; Meade, P.; Neehus, A.L.; Ugurbil, A.C.; Corneau, A.; Kerner, G.; Zhang, P.; Rapaport, F.; Seeleuthner, Y.; Manry, J.; Masson, C.; Schmitt, Y.; Schlüter, A.; Le Voyer, T.; Khan, T.; Li, J.; Fellay, J.; Roussel, L.; Shahrooei, M.; Alosaimi, M.F.; Mansouri, D.; Al-Saud, H.; Al-Mulla, F.; Almourfi, F.; Al-Muhsen, S.Z.; Alsohime, F.; Al Turki, S.; Hasanato, R.; van de Beek, D.; Biondi, A.; Bettini, L.R.; D’Angio’, M.; Bonfanti, P.; Imberti, L.; Sottini, A.; Paghera, S.; Quiros-Roldan, E.; Rossi, C.; Oler, A.J.; Tompkins, M.F.; Alba, C.; Vandernoot, I.; Goffard, J.C.; Smits, G.; Migeotte, I.; Haerynck, F.; Soler-Palacin, P.; Martin-Nalda, A.; Colobran, R.; Morange, P.E.; Keles, S.; Çölkesen, F.; Ozcelik, T.; Yasar, K.K.; Senoglu, S.; Karabela, Ş.N.; Rodríguez-Gallego, C.; Novelli, G.; Hraiech, S.; Tandjaoui-Lambiotte, Y.; Duval, X.; Laouénan, C.; Snow, A.L.; Dalgard, C.L.; Milner, J.D.; Vinh, D.C.; Mogensen, T.H.; Marr, N.; Spaan, A.N.; Boisson, B.; Boisson-Dupuis, S.; Bustamante, J.; Puel, A.; Ciancanelli, M.J.; Meyts, I.; Maniatis, T.; Soumelis, V.; Amara, A.; Nussenzweig, M.; García-Sastre, A.; Krammer, F.; Pujol, A.; Duffy, D.; Lifton, R.P.; Zhang, S.Y.; Gorochov, G.; Béziat, V.; Jouanguy, E.; Sancho-Shimizu, V.; Rice, C.M.; Abel, L.; Notarangelo, L.D.; Cobat, A.; Su, H.C.; Casanova, J.L. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, 2020, 370(6515)eabd4570
[http://dx.doi.org/10.1126/science.abd4570] [PMID: 32972995]
[40]
Meffre, E.; Iwasaki, A. Interferon deficiency can lead to severe COVID. Nature, 2020, 587(7834), 374-376.
[http://dx.doi.org/10.1038/d41586-020-03070-1] [PMID: 33139913]
[41]
Blanco-Melo, D.; Nilsson-Payant, B.E.; Liu, W.C.; Uhl, S.; Hoagland, D.; Møller, R.; Jordan, T.X.; Oishi, K.; Panis, M.; Sachs, D.; Wang, T.T.; Schwartz, R.E.; Lim, J.K.; Albrecht, R.A.; tenOever, B.R. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell, 2020, 181(5), 1036-1045.e9.
[http://dx.doi.org/10.1016/j.cell.2020.04.026] [PMID: 32416070]
[42]
Broggi, A.; Ghosh, S.; Sposito, B.; Spreafico, R.; Balzarini, F.; Lo Cascio, A.; Clementi, N.; De Santis, M.; Mancini, N.; Granucci, F.; Zanoni, I. Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science, 2020, 369(6504), 706-712.
[http://dx.doi.org/10.1126/science.abc3545] [PMID: 32527925]
[43]
Liao, M.; Liu, Y.; Yuan, J.; Wen, Y.; Xu, G.; Zhao, J.; Cheng, L.; Li, J.; Wang, X.; Wang, F.; Liu, L.; Amit, I.; Zhang, S.; Zhang, Z. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med., 2020, 26(6), 842-844.
[http://dx.doi.org/10.1038/s41591-020-0901-9] [PMID: 32398875]
[44]
Zhou, Z.; Ren, L.; Zhang, L.; Zhong, J.; Xiao, Y.; Jia, Z.; Guo, L.; Yang, J.; Wang, C.; Jiang, S.; Yang, D.; Zhang, G.; Li, H.; Chen, F.; Xu, Y.; Chen, M.; Gao, Z.; Yang, J.; Dong, J.; Liu, B.; Zhang, X.; Wang, W.; He, K.; Jin, Q.; Li, M.; Wang, J. Heightened innate immune responses in the respiratory tract of COVID-19 Patients. Cell Host Microbe, 2020, 27(6), 883-890.e2.
[http://dx.doi.org/10.1016/j.chom.2020.04.017] [PMID: 32407669]
[45]
Chua, R.L.; Lukassen, S.; Trump, S.; Hennig, B.P.; Wendisch, D.; Pott, F.; Debnath, O.; Thürmann, L.; Kurth, F.; Völker, M.T.; Kazmierski, J.; Timmermann, B.; Twardziok, S.; Schneider, S.; Machleidt, F.; Müller-Redetzky, H.; Maier, M.; Krannich, A.; Schmidt, S.; Balzer, F.; Liebig, J.; Loske, J.; Suttorp, N.; Eils, J.; Ishaque, N.; Liebert, U.G.; von Kalle, C.; Hocke, A.; Witzenrath, M.; Goffinet, C.; Drosten, C.; Laudi, S.; Lehmann, I.; Conrad, C.; Sander, L.E.; Eils, R. COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nat. Biotechnol., 2020, 38(8), 970-979.
[http://dx.doi.org/10.1038/s41587-020-0602-4] [PMID: 32591762]
[46]
Ziegler, C.G.K.; Allon, S.J.; Nyquist, S.K.; Mbano, I.M.; Miao, V.N.; Tzouanas, C.N.; Cao, Y.; Yousif, A.S.; Bals, J.; Hauser, B.M.; Feldman, J.; Muus, C.; Wadsworth, M.H., II; Kazer, S.W.; Hughes, T.K.; Doran, B.; Gatter, G.J.; Vukovic, M.; Taliaferro, F.; Mead, B.E.; Guo, Z.; Wang, J.P.; Gras, D.; Plaisant, M.; Ansari, M.; Angelidis, I.; Adler, H.; Sucre, J.M.S.; Taylor, C.J.; Lin, B.; Waghray, A.; Mitsialis, V.; Dwyer, D.F.; Buchheit, K.M.; Boyce, J.A.; Barrett, N.A.; Laidlaw, T.M.; Carroll, S.L.; Colonna, L.; Tkachev, V.; Peterson, C.W.; Yu, A.; Zheng, H.B.; Gideon, H.P.; Winchell, C.G.; Lin, P.L.; Bingle, C.D.; Snapper, S.B.; Kropski, J.A.; Theis, F.J.; Schiller, H.B.; Zaragosi, L.E.; Barbry, P.; Leslie, A.; Kiem, H.P.; Flynn, J.L.; Fortune, S.M.; Berger, B.; Finberg, R.W.; Kean, L.S.; Garber, M.; Schmidt, A.G.; Lingwood, D.; Shalek, A.K.; Ordovas-Montanes, J. SARS-CoV-2 Receptor ACE2 Is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell, 2020, 181(5), 1016-1035.e19.
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]
[47]
Onabajo, O.O.; Banday, A.R.; Stanifer, M.L.; Yan, W.; Obajemu, A.; Santer, D.M.; Florez-Vargas, O.; Piontkivska, H.; Vargas, J.M.; Ring, T.J.; Kee, C.; Doldan, P.; Tyrrell, D.L.; Mendoza, J.L.; Boulant, S.; Prokunina-Olsson, L. Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor. Nat. Genet., 2020, 52(12), 1283-1293.
[http://dx.doi.org/10.1038/s41588-020-00731-9] [PMID: 33077916]
[48]
Coles, A.; Lim, M.; Giovannoni, G.; Anderson, P. ABN guidance on the use of disease-modifying therapies in multiple sclerosis in response to the threat of a coronavirus epidemic., 2020.Available from:. https://multiple-sclerosis-research.org/2020/03/abn-guidance-on-dmt-in-the-times-of-covid-19/
[49]
Maguire, C.; Frohman, T.; Zamvil, S.S.; Frohman, E.; Melamed, E. Should interferons take front stage as an essential MS disease-modifying therapy in the era of coronavirus disease 2019? Neurol. Neuroimmunol. Neuroinflamm., 2020, 7(5)e811
[http://dx.doi.org/10.1212/NXI.0000000000000811] [PMID: 32527763]
[50]
Xia, H.; Cao, Z.; Xie, X.; Zhang, X.; Chen, J.Y.; Wang, H.; Menachery, V.D.; Rajsbaum, R.; Shi, P.Y. Evasion of Type I Interferon by SARS-CoV-2. Cell Rep., 2020, 33(1)108234
[http://dx.doi.org/10.1016/j.celrep.2020.108234] [PMID: 32979938]
[51]
Arnon, R.; Aharoni, R. Glatiramer acetate: from bench to bed and back. Isr. Med. Assoc. J., 2019, 21(3), 151-157.
[PMID: 30905097]
[52]
van der Touw, W.; Kang, K.; Luan, Y.; Ma, G.; Mai, S.; Qin, L.; Bian, G.; Zhang, R.; Mungamuri, S.K.; Hu, H.M.; Zhang, C.C.; Aaronson, S.A.; Feldmann, M.; Yang, W.C.; Chen, S.H.; Pan, P.Y. Glatiramer acetate enhances myeloid-derived suppressor cell function via recognition of paired ig-like receptor B. J. Immunol., 2018, 201(6), 1727-1734.
[http://dx.doi.org/10.4049/jimmunol.1701450] [PMID: 30068593]
[53]
Hestvik, A.L.; Skorstad, G.; Price, D.A.; Vartdal, F.; Holmoy, T. Multiple sclerosis: glatiramer acetate induces anti-inflammatory T cells in the cerebrospinal fluid. Mult. Scler., 2008, 14(6), 749-758.
[http://dx.doi.org/10.1177/1352458508089411] [PMID: 18611988]
[54]
Arnon, R.; Aharoni, R. Neuroprotection and neurogeneration in MS and its animal model EAE effected by glatiramer acetate. J. Neural Transm. (Vienna), 2009, 116(11), 1443-1449.
[http://dx.doi.org/10.1007/s00702-009-0272-3] [PMID: 19669693]
[55]
Reick, C.; Ellrichmann, G.; Tsai, T.; Lee, D.H.; Wiese, S.; Gold, R.; Saft, C.; Linker, R.A. Expression of brain-derived neurotrophic factor in astrocytes - Beneficial effects of glatiramer acetate in the R6/2 and YAC128 mouse models of Huntington's disease. Exp Neurol.,, 2016, 285(Pt A), 12-23.
[56]
Azoulay, D.; Vachapova, V.; Shihman, B.; Miler, A.; Karni, A. Lower brain-derived neurotrophic factor in serum of relapsing remitting MS: reversal by glatiramer acetate. J. Neuroimmunol., 2005, 167(1-2), 215-218.
[http://dx.doi.org/10.1016/j.jneuroim.2005.07.001] [PMID: 16083971]
[57]
De Santi, L.; Polimeni, G.; Cuzzocrea, S.; Esposito, E.; Sessa, E.; Annunziata, P.; Bramanti, P. Neuroinflammation and neuroprotection: an update on (future) neurotrophin-related strategies in multiple sclerosis treatment. Curr. Med. Chem., 2011, 18(12), 1775-1784.
[http://dx.doi.org/10.2174/092986711795496881] [PMID: 21466473]
[58]
Zheng, C.; Kar, I.; Chen, C.K.; Sau, C.; Woodson, S.; Serra, A.; Abboud, H. Multiple sclerosis disease-modifying therapy and the COVID-19 pandemic: implications on the risk of infection and future vaccination. CNS Drugs, 2020, 34(9), 879-896.
[http://dx.doi.org/10.1007/s40263-020-00756-y] [PMID: 32780300]
[59]
Comi, G.; Miller, A.E.; Benamor, M.; Truffinet, P.; Poole, E.M.; Freedman, M.S. Characterizing lymphocyte counts and infection rates with long-term teriflunomide treatment: Pooled analysis of clinical trials. Mult. Scler., 2020, 26(9), 1083-1092.
[http://dx.doi.org/10.1177/1352458519851981] [PMID: 31172849]
[60]
Grebenciucova, E.; Pruitt, A. Infections in patients receiving multiple sclerosis disease-modifying therapies. Curr. Neurol. Neurosci. Rep., 2017, 17(11), 88.
[http://dx.doi.org/10.1007/s11910-017-0800-8] [PMID: 28940162]
[61]
Bar-Or, A.; Pachner, A.; Menguy-Vacheron, F.; Kaplan, J.; Wiendl, H. Teriflunomide and its mechanism of action in multiple sclerosis. Drugs, 2014, 74(6), 659-674.
[http://dx.doi.org/10.1007/s40265-014-0212-x] [PMID: 24740824]
[62]
Li, L.; Liu, J.; Delohery, T.; Zhang, D.; Arendt, C.; Jones, C. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro. J. Neuroimmunol., 2013, 265(1-2), 82-90.
[http://dx.doi.org/10.1016/j.jneuroim.2013.10.003] [PMID: 24182769]
[63]
Wostradowski, T.; Prajeeth, C.K.; Gudi, V.; Kronenberg, J.; Witte, S.; Brieskorn, M.; Stangel, M. In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia. J. Neuroinflammation, 2016, 13(1), 250.
[http://dx.doi.org/10.1186/s12974-016-0715-3] [PMID: 27658519]
[64]
Miller, A.E. Oral teriflunomide in the treatment of relapsing forms of multiple sclerosis: clinical evidence and long-term experience. Ther. Adv. Neurol. Disorder., 2017, 10(12), 381-396.
[http://dx.doi.org/10.1177/1756285617722500] [PMID: 29204190]
[65]
Dimitrova, P.; Skapenko, A.; Herrmann, M.L.; Schleyerbach, R.; Kalden, J.R.; Schulze-Koops, H. Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiation. J. Immunol., 2002, 169(6), 3392-3399.
[http://dx.doi.org/10.4049/jimmunol.169.6.3392] [PMID: 12218161]
[66]
Korn, T.; Magnus, T.; Toyka, K.; Jung, S. Modulation of effector cell functions in experimental autoimmune encephalomyelitis by leflunomide--mechanisms independent of pyrimidine depletion. J. Leukoc. Biol., 2004, 76(5), 950-960.
[http://dx.doi.org/10.1189/jlb.0504308] [PMID: 15328336]
[67]
O’Donnell, E.F.; Saili, K.S.; Koch, D.C.; Kopparapu, P.R.; Farrer, D.; Bisson, W.H.; Mathew, L.K.; Sengupta, S.; Kerkvliet, N.I.; Tanguay, R.L.; Kolluri, S.K. The anti-inflammatory drug leflunomide is an agonist of the aryl hydrocarbon receptor. PLoS One, 2010, 5(10)e13128
[http://dx.doi.org/10.1371/journal.pone.0013128] [PMID: 20957046]
[68]
Redaelli, C.; Gaffarogullari, E.C.; Brune, M.; Pilz, C.; Becker, S.; Sonner, J.; Jäschke, A.; Gröne, H.J.; Wick, W.; Platten, M.; Lanz, T.V. Toxicity of teriflunomide in aryl hydrocarbon receptor deficient mice. Biochem. Pharmacol., 2015, 98(3), 484-492.
[http://dx.doi.org/10.1016/j.bcp.2015.08.111] [PMID: 26341389]
[69]
Bar-Or, A.; Freedman, M.S.; Kremenchutzky, M.; Menguy-Vacheron, F.; Bauer, D.; Jodl, S.; Truffinet, P.; Benamor, M.; Chambers, S.; O’Connor, P.W. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology, 2013, 81(6), 552-558.
[http://dx.doi.org/10.1212/WNL.0b013e31829e6fbf] [PMID: 23851964]
[70]
Josephson, M.A.; Gillen, D.; Javaid, B.; Kadambi, P.; Meehan, S.; Foster, P.; Harland, R.; Thistlethwaite, R.J.; Garfinkel, M.; Atwood, W.; Jordan, J.; Sadhu, M.; Millis, M.J.; Williams, J. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation, 2006, 81(5), 704-710.
[http://dx.doi.org/10.1097/01.tp.0000181149.76113.50] [PMID: 16534472]
[71]
Knight, D.A.; Hejmanowski, A.Q.; Dierksheide, J.E.; Williams, J.W.; Chong, A.S.; Waldman, W.J. Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation, 2001, 71(1), 170-174.
[http://dx.doi.org/10.1097/00007890-200101150-00031] [PMID: 11211189]
[72]
Bar-Or, A.; Pender, M.P.; Khanna, R.; Steinman, L.; Hartung, H.P.; Maniar, T.; Croze, E.; Aftab, B.T.; Giovannoni, G.; Joshi, M.A. Epstein-barr virus in multiple sclerosis: theory and emerging immunotherapies. Trends Mol. Med., 2020, 26(3), 296-310.
[http://dx.doi.org/10.1016/j.molmed.2019.11.003] [PMID: 31862243]
[73]
Bilger, A.; Plowshay, J.; Ma, S.; Nawandar, D.; Barlow, E.A.; Romero-Masters, J.C.; Bristol, J.A.; Li, Z.; Tsai, M.H.; Delecluse, H.J.; Kenney, S.C. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication. Oncotarget, 2017, 8(27), 44266-44280.
[http://dx.doi.org/10.18632/oncotarget.17863] [PMID: 28574826]
[74]
Gilli, F.; Li, L.; Royce, D.B.; DiSano, K.D.; Pachner, A.R. Treatment of Theiler’s virus-induced demyelinating disease with teriflunomide. J. Neurovirol., 2017, 23(6), 825-838.
[http://dx.doi.org/10.1007/s13365-017-0570-8] [PMID: 28913765]
[75]
Xiong, R.; Zhang, L.; Li, S.; Sun, Y.; Ding, M.; Wang, Y.; Zhao, Y.; Wu, Y.; Shang, W.; Jiang, X.; Shan, J.; Shen, Z.; Tong, Y.; Xu, L.; Chen, Y.; Liu, Y.; Zou, G.; Lavillete, D.; Zhao, Z.; Wang, R.; Zhu, L.; Xiao, G.; Lan, K.; Li, H.; Xu, K. Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2. Protein Cell, 2020, 11(10), 723-739.
[http://dx.doi.org/10.1007/s13238-020-00768-w] [PMID: 32754890]
[76]
Möhn, N.; Saker, F.; Bonda, V.; Respondek, G.; Bachmann, M.; Stoll, M.; Wattjes, M.P.; Stangel, M.; Skripuletz, T. Mild COVID-19 symptoms despite treatment with teriflunomide and high-dose methylprednisolone due to multiple sclerosis relapse. J. Neurol., 2020, 267(10), 2803-2805.
[http://dx.doi.org/10.1007/s00415-020-09921-1] [PMID: 32494855]
[77]
Maghzi, A.H.; Houtchens, M.K.; Preziosa, P.; Ionete, C.; Beretich, B.D.; Stankiewicz, J.M.; Tauhid, S.; Cabot, A.; Berriosmorales, I.; Schwartz, T.H.W.; Sloane, J.A.; Freedman, M.S.; Filippi, M.; Weiner, H.L.; Bakshi, R. COVID-19 in teriflunomide-treated patients with multiple sclerosis. J. Neurol., 2020, 267(10), 2790-2796.
[http://dx.doi.org/10.1007/s00415-020-09944-8] [PMID: 32494856]
[78]
Mantero, V.; Baroncini, D.; Balgera, R.; Guaschino, C.; Basilico, P.; Annovazzi, P.; Zaffaroni, M.; Salmaggi, A.; Cordano, C. Mild COVID-19 infection in a group of teriflunomide-treated patients with multiple sclerosis. J. Neurol., 2020, 1-2.
[http://dx.doi.org/10.1007/s00415-020-10196-9] [PMID: 32865629]
[79]
Ciardi, M.R.; Zingaropoli, M.A.; Pasculli, P.; Perri, V.; Tartaglia, M.; Valeri, S.; Russo, G.; Conte, A.; Mastroianni, C.M. The peripheral blood immune cell profile in a teriflunomide-treated multiple sclerosis patient with COVID-19 pneumonia. J. Neuroimmunol., 2020, 346577323
[http://dx.doi.org/10.1016/j.jneuroim.2020.577323] [PMID: 32688146]
[80]
Burness, C.B.; Deeks, E.D. Dimethyl fumarate: a review of its use in patients with relapsing-remitting multiple sclerosis. CNS Drugs, 2014, 28(4), 373-387.
[http://dx.doi.org/10.1007/s40263-014-0155-5] [PMID: 24623127]
[81]
Montes Diaz, G.; Hupperts, R.; Fraussen, J.; Somers, V. Dimethyl fumarate treatment in multiple sclerosis: Recent advances in clinical and immunological studies. Autoimmun. Rev., 2018, 17(12), 1240-1250.
[http://dx.doi.org/10.1016/j.autrev.2018.07.001] [PMID: 30316988]
[82]
Hosseini, A.; Masjedi, A.; Baradaran, B.; Hojjat-Farsangi, M.; Ghalamfarsa, G.; Anvari, E.; Jadidi-Niaragh, F. Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis. J. Cell. Physiol., 2019, 234(7), 9943-9955.
[http://dx.doi.org/10.1002/jcp.27930] [PMID: 30536402]
[83]
Kornberg, M.D.; Bhargava, P.; Kim, P.M.; Putluri, V.; Snowman, A.M.; Putluri, N.; Calabresi, P.A.; Snyder, S.H. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science, 2018, 360(6387), 449-453.
[http://dx.doi.org/10.1126/science.aan4665] [PMID: 29599194]
[84]
Schmidt, T.J.; Ak, M.; Mrowietz, U. Reactivity of dimethyl fumarate and methylhydrogen fumarate towards glutathione and N-acetyl-L-cysteine--preparation of S-substituted thiosuccinic acid esters. Bioorg. Med. Chem., 2007, 15(1), 333-342.
[http://dx.doi.org/10.1016/j.bmc.2006.09.053] [PMID: 17049250]
[85]
Hammer, A.; Waschbisch, A.; Knippertz, I.; Zinser, E.; Berg, J.; Jörg, S.; Kuhbandner, K.; David, C.; Pi, J.; Bayas, A.; Lee, D.H.; Haghikia, A.; Gold, R.; Steinkasserer, A.; Linker, R.A. Role of nuclear factor (erythroid-derived 2)-like 2 signaling for effects of fumaric acid esters on dendritic cells. Front. Immunol., 2017, 8, 1922.
[http://dx.doi.org/10.3389/fimmu.2017.01922] [PMID: 29312359]
[86]
Olagnier, D.; Farahani, E.; Thyrsted, J.; Blay-Cadanet, J.; Herengt, A.; Idorn, M.; Hait, A.; Hernaez, B.; Knudsen, A.; Iversen, M.B.; Schilling, M.; Jørgensen, S.E.; Thomsen, M.; Reinert, L.S.; Lappe, M.; Hoang, H.D.; Gilchrist, V.H.; Hansen, A.L.; Ottosen, R.; Nielsen, C.G.; Møller, C.; van der Horst, D.; Peri, S.; Balachandran, S.; Huang, J.; Jakobsen, M.; Svenningsen, E.B.; Poulsen, T.B.; Bartsch, L.; Thielke, A.L.; Luo, Y.; Alain, T.; Rehwinkel, J.; Alcamí, A.; Hiscott, J.; Mogensen, T.H.; Paludan, S.R.; Holm, C.K. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat. Commun., 2020, 11(1), 4938.
[http://dx.doi.org/10.1038/s41467-020-18764-3] [PMID: 33009401]
[87]
Chen, H.; Assmann, J.C.; Krenz, A.; Rahman, M.; Grimm, M.; Karsten, C.M.; Köhl, J.; Offermanns, S.; Wettschureck, N.; Schwaninger, M. Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE. J. Clin. Invest., 2014, 124(5), 2188-2192.
[http://dx.doi.org/10.1172/JCI72151] [PMID: 24691444]
[88]
Grzegorzewska, A.P.; Seta, F.; Han, R.; Czajka, C.A.; Makino, K.; Stawski, L.; Isenberg, J.S.; Browning, J.L.; Trojanowska, M. Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways. Sci. Rep., 2017, 7, 41605.
[http://dx.doi.org/10.1038/srep41605] [PMID: 28150703]
[89]
Lin, S.X.; Lisi, L.; Dello Russo, C.; Polak, P.E.; Sharp, A.; Weinberg, G.; Kalinin, S.; Feinstein, D.L. The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro, 2011, 3(2)e00055
[http://dx.doi.org/10.1042/AN20100033] [PMID: 21382015]
[90]
Parodi, B.; Rossi, S.; Morando, S.; Cordano, C.; Bragoni, A.; Motta, C.; Usai, C.; Wipke, B.T.; Scannevin, R.H.; Mancardi, G.L.; Centonze, D.; Kerlero de Rosbo, N.; Uccelli, A. Fumarates modulate microglia activation through a novel HCAR2 signaling pathway and rescue synaptic dysregulation in inflamed CNS. Acta Neuropathol., 2015, 130(2), 279-295.
[http://dx.doi.org/10.1007/s00401-015-1422-3] [PMID: 25920452]
[91]
Putzki, N.; Baranwal, M.K.; Tettenborn, B.; Limmroth, V.; Kreuzfelder, E. Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells. Eur. Neurol., 2010, 63(5), 311-317.
[http://dx.doi.org/10.1159/000302687] [PMID: 20453514]
[92]
Planas, R.; Jelčić, I.; Schippling, S.; Martin, R.; Sospedra, M. Natalizumab treatment perturbs memory- and marginal zone-like B-cell homing in secondary lymphoid organs in multiple sclerosis. Eur. J. Immunol., 2012, 42(3), 790-798.
[http://dx.doi.org/10.1002/eji.201142108] [PMID: 22144343]
[93]
Mattoscio, M.; Nicholas, R.; Sormani, M.P.; Malik, O.; Lee, J.S.; Waldman, A.D.; Dazzi, F.; Muraro, P.A. Hematopoietic mobilization: Potential biomarker of response to natalizumab in multiple sclerosis. Neurology, 2015, 84(14), 1473-1482.
[http://dx.doi.org/10.1212/WNL.0000000000001454] [PMID: 25762712]
[94]
Shenoy, E.S.; Mylonakis, E.; Hurtado, R.M.; Venna, N. Natalizumab and HSV meningitis. J. Neurovirol., 2011, 17(3), 288-290.
[http://dx.doi.org/10.1007/s13365-011-0027-4] [PMID: 21487835]
[95]
Fine, A.J.; Sorbello, A.; Kortepeter, C.; Scarazzini, L. Central nervous system herpes simplex and varicella zoster virus infections in natalizumab-treated patients. Clin. Infect. Dis., 2013, 57(6), 849-852.
[http://dx.doi.org/10.1093/cid/cit376] [PMID: 23728144]
[96]
Moiola, L.; Barcella, V.; Benatti, S.; Capobianco, M.; Capra, R.; Cinque, P.; Comi, G.; Fasolo, M.M.; Franzetti, F.; Galli, M.; Gerevini, S.; Meroni, L.; Origoni, M.; Prosperini, L.; Puoti, M.; Scarpazza, C.; Tortorella, C.; Zaffaroni, M.; Riva, A. The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement. Mult. Scler., 2020.1352458520952311
[PMID: 32940121]
[97]
Lamers, M.M.; Beumer, J.; van der Vaart, J.; Knoops, K.; Puschhof, J.; Breugem, T.I.; Ravelli, R.B.G.; Paul van Schayck, J.; Mykytyn, A.Z.; Duimel, H.Q.; van Donselaar, E.; Riesebosch, S.; Kuijpers, H.J.H.; Schipper, D.; van de Wetering, W.J.; de Graaf, M.; Koopmans, M.; Cuppen, E.; Peters, P.J.; Haagmans, B.L.; Clevers, H. SARS-CoV-2 productively infects human gut enterocytes. Science, 2020, 369(6499), 50-54.
[http://dx.doi.org/10.1126/science.abc1669] [PMID: 32358202]
[98]
Rimmer, K.; Farber, R.; Thakur, K.; Braverman, G.; Podolsky, D.; Sutherland, L.; Migliore, C.; Ryu, Y.K.; Levin, S.; De Jager, P.L.; Vargas, W.; Levine, L.; Riley, C.S. Fatal COVID-19 in an MS patient on natalizumab: A case report. Mult. Scler. J. Exp. Transl. Clin., 2020, 6(3)2055217320942931
[http://dx.doi.org/10.1177/2055217320942931] [PMID: 32850133]
[99]
Loonstra, F.C.; Hoitsma, E.; van Kempen, Z.L.; Killestein, J.; Mostert, J.P. COVID-19 in multiple sclerosis: The Dutch experience. Mult. Scler., 2020, 26(10), 1256-1260.
[http://dx.doi.org/10.1177/1352458520942198] [PMID: 32662742]
[100]
Aguirre, C.; Meca-Lallana, V.; Barrios-Blandino, A.; Del Río, B.; Vivancos, J. Covid-19 in a patient with multiple sclerosis treated with natalizumab: May the blockade of integrins have a protective role? Mult. Scler. Relat. Disord., 2020, 44102250
[http://dx.doi.org/10.1016/j.msard.2020.102250] [PMID: 32531754]
[101]
Borriello, G.; Ianniello, A. COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach. Mult. Scler. Relat. Disord., 2020, 41102165
[http://dx.doi.org/10.1016/j.msard.2020.102165] [PMID: 32388451]
[102]
Shukla, A.K.; Westfield, G.H.; Xiao, K.; Reis, R.I.; Huang, L.Y.; Tripathi-Shukla, P.; Qian, J.; Li, S.; Blanc, A.; Oleskie, A.N.; Dosey, A.M.; Su, M.; Liang, C.R.; Gu, L.L.; Shan, J.M.; Chen, X.; Hanna, R.; Choi, M.; Yao, X.J.; Klink, B.U.; Kahsai, A.W.; Sidhu, S.S.; Koide, S.; Penczek, P.A.; Kossiakoff, A.A.; Woods, V.L., Jr; Kobilka, B.K.; Skiniotis, G.; Lefkowitz, R.J. Visualization of arrestin recruitment by a G-protein-coupled receptor. Nature, 2014, 512(7513), 218-222.
[http://dx.doi.org/10.1038/nature13430] [PMID: 25043026]
[103]
Spiegel, S.; Milstien, S. The outs and the ins of sphingosine-1-phosphate in immunity. Nat. Rev. Immunol., 2011, 11(6), 403-415.
[http://dx.doi.org/10.1038/nri2974] [PMID: 21546914]
[104]
David, O.J.; Kovarik, J.M.; Schmouder, R.L. Clinical pharmacokinetics of fingolimod. Clin. Pharmacokinet., 2012, 51(1), 15-28.
[http://dx.doi.org/10.2165/11596550-000000000-00000] [PMID: 22149256]
[105]
David, O.J.; Behrje, R.; Pal, P.; Hara, H.; Lates, C.D.; Schmouder, R. Pharmacokinetic interaction between fingolimod and carbamazepine in healthy subjects. Clin. Pharmacol. Drug Dev., 2018, 7(6), 575-586.
[http://dx.doi.org/10.1002/cpdd.459] [PMID: 29694732]
[106]
Barry, B.; Erwin, A.A.; Stevens, J.; Tornatore, C. Fingolimod rebound: a review of the clinical experience and management considerations. Neurol. Ther., 2019, 8(2), 241-250.
[http://dx.doi.org/10.1007/s40120-019-00160-9] [PMID: 31677060]
[107]
Meissner, A.; Miro, F.; Jiménez-Altayó, F.; Jurado, A.; Vila, E.; Planas, A.M. Sphingosine-1-phosphate signalling-a key player in the pathogenesis of Angiotensin II-induced hypertension. Cardiovasc. Res., 2017, 113(2), 123-133.
[http://dx.doi.org/10.1093/cvr/cvw256] [PMID: 28082452]
[108]
Ohkura, S.I.; Usui, S.; Takashima, S.I.; Takuwa, N.; Yoshioka, K.; Okamoto, Y.; Inagaki, Y.; Sugimoto, N.; Kitano, T.; Takamura, M.; Wada, T.; Kaneko, S.; Takuwa, Y. Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6. PLoS One, 2017, 12(8)e0182329
[http://dx.doi.org/10.1371/journal.pone.0182329] [PMID: 28771545]
[109]
Hamming, I.; Timens, W.; Bulthuis, M.L.; Lely, A.T.; Navis, G.; van Goor, H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol., 2004, 203(2), 631-637.
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[110]
Lukassen, S.; Chua, R.L.; Trefzer, T.; Kahn, N.C.; Schneider, M.A.; Muley, T.; Winter, H.; Meister, M.; Veith, C.; Boots, A.W.; Hennig, B.P.; Kreuter, M.; Conrad, C.; Eils, R. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J., 2020, 39(10)e105114
[http://dx.doi.org/10.15252/embj.2020105114] [PMID: 32246845]
[111]
Kimball, A.; Hatfield, K.M.; Arons, M.; James, A.; Taylor, J.; Spicer, K.; Bardossy, A.C.; Oakley, L.P.; Tanwar, S.; Chisty, Z.; Bell, J.M.; Methner, M.; Harney, J.; Jacobs, J.R.; Carlson, C.M.; McLaughlin, H.P.; Stone, N.; Clark, S.; Brostrom-Smith, C.; Page, L.C.; Kay, M.; Lewis, J.; Russell, D.; Hiatt, B.; Gant, J.; Duchin, J.S.; Clark, T.A.; Honein, M.A.; Reddy, S.C.; Jernigan, J.A. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - King County, Washington, March 2020. MMWR Morb. Mortal. Wkly. Rep., 2020, 69(13), 377-381.
[http://dx.doi.org/10.15585/mmwr.mm6913e1] [PMID: 32240128]
[112]
Liu, G.; Burns, S.; Huang, G.; Boyd, K.; Proia, R.L.; Flavell, R.A.; Chi, H. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat. Immunol., 2009, 10(7), 769-777.
[http://dx.doi.org/10.1038/ni.1743] [PMID: 19483717]
[113]
Rahman, M.M.; Prünte, L.; Lebender, L.F.; Patel, B.S.; Gelissen, I.; Hansbro, P.M.; Morris, J.C.; Clark, A.R.; Verrills, N.M.; Ammit, A.J. The phosphorylated form of FTY720 activates PP2A, represses inflammation and is devoid of S1P agonism in A549 lung epithelial cells. Sci. Rep., 2016, 6, 37297.
[http://dx.doi.org/10.1038/srep37297] [PMID: 27849062]
[114]
Walsh, K.B.; Teijaro, J.R.; Wilker, P.R.; Jatzek, A.; Fremgen, D.M.; Das, S.C.; Watanabe, T.; Hatta, M.; Shinya, K.; Suresh, M.; Kawaoka, Y.; Rosen, H.; Oldstone, M.B. Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus. Proc. Natl. Acad. Sci. USA, 2011, 108(29), 12018-12023.
[http://dx.doi.org/10.1073/pnas.1107024108] [PMID: 21715659]
[115]
Garcia, J.G.; Liu, F.; Verin, A.D.; Birukova, A.; Dechert, M.A.; Gerthoffer, W.T.; Bamberg, J.R.; English, D. Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J. Clin. Invest., 2001, 108(5), 689-701.
[http://dx.doi.org/10.1172/JCI12450] [PMID: 11544274]
[116]
Natarajan, V.; Dudek, S.M.; Jacobson, J.R.; Moreno-Vinasco, L.; Huang, L.S.; Abassi, T.; Mathew, B.; Zhao, Y.; Wang, L.; Bittman, R.; Weichselbaum, R.; Berdyshev, E.; Garcia, J.G. Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury. Am. J. Respir. Cell Mol. Biol., 2013, 49(1), 6-17.
[http://dx.doi.org/10.1165/rcmb.2012-0411TR] [PMID: 23449739]
[117]
Singer, I.I.; Tian, M.; Wickham, L.A.; Lin, J.; Matheravidathu, S.S.; Forrest, M.J.; Mandala, S.; Quackenbush, E.J. Sphingosine-1-phosphate agonists increase macrophage homing, lymphocyte contacts, and endothelial junctional complex formation in murine lymph nodes. J. Immunol., 2005, 175(11), 7151-7161.
[http://dx.doi.org/10.4049/jimmunol.175.11.7151] [PMID: 16301618]
[118]
Brinkmann, V.; Cyster, J.G.; Hla, T. FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am. J. Transplant., 2004, 4(7), 1019-1025.
[http://dx.doi.org/10.1111/j.1600-6143.2004.00476.x] [PMID: 15196057]
[119]
Wang, L.; Chiang, E.T.; Simmons, J.T.; Garcia, J.G.; Dudek, S.M. FTY720-induced human pulmonary endothelial barrier enhancement is mediated by c-Abl. Eur. Respir. J., 2011, 38(1), 78-88.
[http://dx.doi.org/10.1183/09031936.00047810] [PMID: 21071472]
[120]
Hardingham, G.E.; Bading, H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat. Rev. Neurosci., 2010, 11(10), 682-696.
[http://dx.doi.org/10.1038/nrn2911] [PMID: 20842175]
[121]
Joshi, P.; Gabrielli, M.; Ponzoni, L.; Pelucchi, S.; Stravalaci, M.; Beeg, M.; Mazzitelli, S.; Braida, D.; Sala, M.; Boda, E.; Buffo, A.; Gobbi, M.; Gardoni, F.; Matteoli, M.; Marcello, E.; Verderio, C. Fingolimod limits acute Aβ neurotoxicity and promotes synaptic versus extrasynaptic NMDA receptor functionality in hippocampal neurons. Sci. Rep., 2017, 7, 41734.
[http://dx.doi.org/10.1038/srep41734] [PMID: 28134307]
[122]
Deogracias, R.; Yazdani, M.; Dekkers, M.P.; Guy, J.; Ionescu, M.C.; Vogt, K.E.; Barde, Y.A. Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc. Natl. Acad. Sci. USA, 2012, 109(35), 14230-14235.
[http://dx.doi.org/10.1073/pnas.1206093109] [PMID: 22891354]
[123]
Di Menna, L.; Molinaro, G.; Di Nuzzo, L.; Riozzi, B.; Zappulla, C.; Pozzilli, C.; Turrini, R.; Caraci, F.; Copani, A.; Battaglia, G.; Nicoletti, F.; Bruno, V. Fingolimod protects cultured cortical neurons against excitotoxic death. Pharmacol. Res., 2013, 67(1), 1-9.
[http://dx.doi.org/10.1016/j.phrs.2012.10.004] [PMID: 23073075]
[124]
di Nuzzo, L.; Orlando, R.; Tognoli, C.; Di Pietro, P.; Bertini, G.; Miele, J.; Bucci, D.; Motolese, M.; Scaccianoce, S.; Caruso, A.; Mauro, G.; De Lucia, C.; Battaglia, G.; Bruno, V.; Fabene, P.F.; Nicoletti, F. Antidepressant activity of fingolimod in mice. Pharmacol. Res. Perspect., 2015, 3(3)e00135
[http://dx.doi.org/10.1002/prp2.135] [PMID: 26171219]
[125]
Asadi-Pooya, A.A.; Simani, L. Central nervous system manifestations of COVID-19: A systematic review. J. Neurol. Sci., 2020, 413116832
[http://dx.doi.org/10.1016/j.jns.2020.116832] [PMID: 32299017]
[126]
Stecchi, S.; Scandellari, C.; Gabrielli, L.; Lazzarotto, T. Recommendations for fingolimod treated patients vacinated for varicella zoster virus. Neurology, 2014, 82.
[127]
Kappos, L.; Mehling, M.; Arroyo, R.; Izquierdo, G.; Selmaj, K.; Curovic-Perisic, V.; Keil, A.; Bijarnia, M.; Singh, A.; von Rosenstiel, P. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology, 2015, 84(9), 872-879.
[http://dx.doi.org/10.1212/WNL.0000000000001302] [PMID: 25636714]
[128]
Gajofatto, A. Spotlight on siponimod and its potential in the treatment of secondary progressive multiple sclerosis: the evidence to date. Drug Des. Devel. Ther., 2017, 11, 3153-3157.
[http://dx.doi.org/10.2147/DDDT.S122249] [PMID: 29138536]
[129]
Goodman, A.D.; Anadani, N.; Gerwitz, L. Siponimod in the treatment of multiple sclerosis. Expert Opin. Investig. Drugs, 2019, 28(12), 1051-1057.
[http://dx.doi.org/10.1080/13543784.2019.1676725] [PMID: 31603362]
[130]
Hu, Y.; Turner, M.J.; Shields, J.; Gale, M.S.; Hutto, E.; Roberts, B.L.; Siders, W.M.; Kaplan, J.M. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology, 2009, 128(2), 260-270.
[http://dx.doi.org/10.1111/j.1365-2567.2009.03115.x] [PMID: 19740383]
[131]
Evan, J.R.; Bozkurt, S.B.; Thomas, N.C.; Bagnato, F. Alemtuzumab for the treatment of multiple sclerosis. Expert Opin. Biol. Ther., 2018, 18(3), 323-334.
[http://dx.doi.org/10.1080/14712598.2018.1425388] [PMID: 29309202]
[132]
Thomas, K.; Eisele, J.; Rodriguez-Leal, F.A.; Hainke, U.; Ziemssen, T. Acute effects of alemtuzumab infusion in patients with active relapsing-remitting MS. Neurol. Neuroimmunol. Neuroinflamm., 2016, 3(3)e228
[http://dx.doi.org/10.1212/NXI.0000000000000228] [PMID: 27213173]
[133]
Zhang, X.; Tao, Y.; Chopra, M.; Ahn, M.; Marcus, K.L.; Choudhary, N.; Zhu, H.; Markovic-Plese, S. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J. Immunol., 2013, 191(12), 5867-5874.
[http://dx.doi.org/10.4049/jimmunol.1301926] [PMID: 24198283]
[134]
Baker, D.; Herrod, S.S.; Alvarez-Gonzalez, C.; Giovannoni, G.; Schmierer, K. Interpreting lymphocyte reconstitution data from the pivotal phase 3 Trials of Alemtuzumab. JAMA Neurol., 2017, 74(8), 961-969.
[http://dx.doi.org/10.1001/jamaneurol.2017.0676] [PMID: 28604916]
[135]
Akgün, K.; Blankenburg, J.; Marggraf, M.; Haase, R.; Ziemssen, T. Event-Driven Immunoprofiling predicts return of disease activity in Alemtuzumab-treated multiple sclerosis. Front. Immunol., 2020, 11, 56.
[http://dx.doi.org/10.3389/fimmu.2020.00056] [PMID: 32082320]
[136]
Carandini, T.; Pietroboni, A.M.; Sacchi, L.; De Riz, M.A.; Pozzato, M.; Arighi, A.; Fumagalli, G.G.; Martinelli Boneschi, F.; Galimberti, D.; Scarpini, E. Alemtuzumab in multiple sclerosis during the COVID-19 pandemic: A mild uncomplicated infection despite intense immunosuppression. Mult. Scler., 2020, 26(10), 1268-1269.
[http://dx.doi.org/10.1177/1352458520926459] [PMID: 32463329]
[137]
Guevara, C.; Villa, E.; Cifuentes, M.; Naves, R.; Grazia, J. Mild COVID-19 infection in a patient with multiple sclerosis and severe depletion of T-lymphocyte subsets due to alemtuzumab. Mult. Scler. Relat. Disord., 2020, 44102314
[http://dx.doi.org/10.1016/j.msard.2020.102314] [PMID: 32593959]
[138]
Fernández-Díaz, E.; Gracia-Gil, J.; García-García, J.G.; Palao, M.; Romero-Sánchez, C.M.; Segura, T. COVID-19 and multiple sclerosis: A description of two cases on alemtuzumab. Mult. Scler. Relat. Disord., 2020, 45102402
[http://dx.doi.org/10.1016/j.msard.2020.102402] [PMID: 32711297]
[139]
Fiorella, C.; Lorna, G. COVID-19 in a multiple sclerosis (MS) patient treated with alemtuzumab: Insight to the immune response after COVID. Mult. Scler. Relat. Disord., 2020, 46102447
[http://dx.doi.org/10.1016/j.msard.2020.102447] [PMID: 32835901]
[140]
Coles, A.J.; Cohen, J.A.; Fox, E.J.; Giovannoni, G.; Hartung, H.P.; Havrdova, E.; Schippling, S.; Selmaj, K.W.; Traboulsee, A.; Compston, D.A.S.; Margolin, D.H.; Thangavelu, K.; Chirieac, M.C.; Jody, D.; Xenopoulos, P.; Hogan, R.J.; Panzara, M.A.; Arnold, D.L. Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology, 2017, 89(11), 1117-1126.
[http://dx.doi.org/10.1212/WNL.0000000000004354] [PMID: 28835403]
[141]
Fox, E.J.; Buckle, G.J.; Singer, B.; Singh, V.; Boster, A. Lymphopenia and DMTs for relapsing forms of MS: Considerations for the treating neurologist. Neurol. Clin. Pract., 2019, 9(1), 53-63.
[http://dx.doi.org/10.1212/CPJ.0000000000000567] [PMID: 30859008]
[142]
Bar-Or, A.; Calkwood, J.C.; Chognot, C.; Evershed, J.; Fox, E.J.; Herman, A.; Manfrini, M.; McNamara, J.; Robertson, D.S.; Stokmaier, D.; Wendt, J.K.; Winthrop, K.L.; Traboulsee, A. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology, 2020, 95(14), e1999-e2008.
[http://dx.doi.org/10.1212/WNL.0000000000010380] [PMID: 32727835]
[143]
Novi, G.; Mikulska, M.; Briano, F.; Toscanini, F.; Tazza, F.; Uccelli, A.; Inglese, M. COVID-19 in a MS patient treated with ocrelizumab: does immunosuppression have a protective role? Mult. Scler. Relat. Disord., 2020, 42102120
[http://dx.doi.org/10.1016/j.msard.2020.102120] [PMID: 32315980]
[144]
Wurm, H.; Attfield, K.; Iversen, A.K.; Gold, R.; Fugger, L.; Haghikia, A. Recovery from COVID-19 in a B-cell-depleted multiple sclerosis patient. Mult. Scler., 2020, 26(10), 1261-1264.
[http://dx.doi.org/10.1177/1352458520943791] [PMID: 32762494]
[145]
Suwanwongse, K.; Shabarek, N. Benign course of COVID-19 in a multiple sclerosis patient treated with Ocrelizumab. Mult. Scler. Relat. Disord., 2020, 42102201
[http://dx.doi.org/10.1016/j.msard.2020.102201] [PMID: 32480327]
[146]
Montero-Escribano, P.; Matías-Guiu, J.; Gómez-Iglesias, P.; Porta-Etessam, J.; Pytel, V.; Matias-Guiu, J.A. Anti-CD20 and COVID-19 in multiple sclerosis and related disorders: A case series of 60 patients from Madrid, Spain. Mult. Scler. Relat. Disord., 2020, 42102185
[http://dx.doi.org/10.1016/j.msard.2020.102185] [PMID: 32408147]
[147]
Barr, T.A.; Shen, P.; Brown, S.; Lampropoulou, V.; Roch, T.; Lawrie, S.; Fan, B.; O’Connor, R.A.; Anderton, S.M.; Bar-Or, A.; Fillatreau, S.; Gray, D. B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J. Exp. Med., 2012, 209(5), 1001-1010.
[http://dx.doi.org/10.1084/jem.20111675] [PMID: 22547654]
[148]
Safavi, F.; Nourbakhsh, B.; Azimi, A.R. B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Mult. Scler. Relat. Disord., 2020, 43102195
[http://dx.doi.org/10.1016/j.msard.2020.102195] [PMID: 32460086]
[149]
Wijnands, J.M.A.; Zhu, F.; Kingwell, E.; Fisk, J.D.; Evans, C.; Marrie, R.A.; Zhao, Y.; Tremlett, H. Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study. J. Neurol. Neurosurg. Psychiatry, 2018, 89(10), 1050-1056.
[http://dx.doi.org/10.1136/jnnp-2017-317493] [PMID: 29602795]
[150]
Chen, Z.; John Wherry, E. T cell responses in patients with COVID-19. Nat. Rev. Immunol., 2020, 20(9), 529-536.
[http://dx.doi.org/10.1038/s41577-020-0402-6] [PMID: 32728222]
[151]
Grifoni, A.; Weiskopf, D.; Ramirez, S.I.; Mateus, J.; Dan, J.M.; Moderbacher, C.R.; Rawlings, S.A.; Sutherland, A.; Premkumar, L.; Jadi, R.S.; Marrama, D.; de Silva, A.M.; Frazier, A.; Carlin, A.F.; Greenbaum, J.A.; Peters, B.; Krammer, F.; Smith, D.M.; Crotty, S.; Sette, A. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell, 2020, 181(7), 1489-1501.e15.
[http://dx.doi.org/10.1016/j.cell.2020.05.015] [PMID: 32473127]
[152]
Sekine, T.; Perez-Potti, A.; Rivera-Ballesteros, O.; Strålin, K.; Gorin, J.B.; Olsson, A.; Llewellyn-Lacey, S.; Kamal, H.; Bogdanovic, G.; Muschiol, S.; Wullimann, D.J.; Kammann, T.; Emgård, J.; Parrot, T.; Folkesson, E.; Rooyackers, O.; Eriksson, L.I.; Henter, J.I.; Sönnerborg, A.; Allander, T.; Albert, J.; Nielsen, M.; Klingström, J.; Gredmark-Russ, S.; Björkström, N.K.; Sandberg, J.K.; Price, D.A.; Ljunggren, H.G.; Aleman, S.; Buggert, M.; Robust, T. Cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell, 2020, 183(1), 158-168.e14.
[http://dx.doi.org/10.1016/j.cell.2020.08.017] [PMID: 32979941]
[153]
Wang, B.; Wang, L.; Kong, X.; Geng, J.; Xiao, D.; Ma, C.; Jiang, X.M.; Wang, P.H. Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients. J. Med. Virol., 2020, 92(9), 1684-1689.
[http://dx.doi.org/10.1002/jmv.25946] [PMID: 32343415]
[154]
Diao, B.; Wang, C.; Tan, Y.; Chen, X.; Liu, Y.; Ning, L.; Chen, L.; Li, M.; Liu, Y.; Wang, G.; Yuan, Z.; Feng, Z.; Zhang, Y.; Wu, Y.; Chen, Y. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front. Immunol., 2020, 11, 827.
[http://dx.doi.org/10.3389/fimmu.2020.00827] [PMID: 32425950]
[155]
Kaneko, N.; Kuo, H.H.; Boucau, J.; Farmer, J.R.; Allard-Chamard, H.; Mahajan, V.S.; Piechocka-Trocha, A.; Lefteri, K.; Osborn, M.; Bals, J.; Bartsch, Y.C.; Bonheur, N.; Caradonna, T.M.; Chevalier, J.; Chowdhury, F.; Diefenbach, T.J.; Einkauf, K.; Fallon, J.; Feldman, J.; Finn, K.K.; Garcia-Broncano, P.; Hartana, C.A.; Hauser, B.M.; Jiang, C.; Kaplonek, P.; Karpell, M.; Koscher, E.C.; Lian, X.; Liu, H.; Liu, J.; Ly, N.L.; Michell, A.R.; Rassadkina, Y.; Seiger, K.; Sessa, L.; Shin, S.; Singh, N.; Sun, W.; Sun, X.; Ticheli, H.J.; Waring, M.T.; Zhu, A.L.; Alter, G.; Li, J.Z.; Lingwood, D.; Schmidt, A.G.; Lichterfeld, M.; Walker, B.D.; Yu, X.G.; Padera, R.F., Jr; Pillai, S. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell, 2020, 183(1), 143-157.e13.
[http://dx.doi.org/10.1016/j.cell.2020.08.025] [PMID: 32877699]
[156]
Woodruff, M.C.; Ramonell, R.P.; Nguyen, D.C.; Cashman, K.S.; Saini, A.S.; Haddad, N.S.; Ley, A.M.; Kyu, S.; Howell, J.C.; Ozturk, T.; Lee, S.; Suryadevara, N.; Case, J.B.; Bugrovsky, R.; Chen, W.; Estrada, J.; Morrison-Porter, A.; Derrico, A.; Anam, F.A.; Sharma, M.; Wu, H.M.; Le, S.N.; Jenks, S.A.; Tipton, C.M.; Staitieh, B.; Daiss, J.L.; Ghosn, E.; Diamond, M.S.; Carnahan, R.H.; Crowe, J.E., Jr; Hu, W.T.; Lee, F.E.; Sanz, I. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nat. Immunol., 2020, 21(12), 1506-1516.
[http://dx.doi.org/10.1038/s41590-020-00814-z] [PMID: 33028979]
[157]
Shrock, E.; Fujimura, E.; Kula, T.; Timms, R.T.; Lee, I.H.; Leng, Y.; Robinson, M.L.; Sie, B.M.; Li, M.Z.; Chen, Y.; Logue, J.; Zuiani, A.; McCulloch, D.; Lelis, F.J.N.; Henson, S.; Monaco, D.R.; Travers, M.; Habibi, S.; Clarke, W.A.; Caturegli, P.; Laeyendecker, O.; Piechocka-Trocha, A.; Li, J.Z.; Khatri, A.; Chu, H.Y.; Villani, A.C.; Kays, K.; Goldberg, M.B.; Hacohen, N.; Filbin, M.R.; Yu, X.G.; Walker, B.D.; Wesemann, D.R.; Larman, H.B.; Lederer, J.A.; Elledge, S.J. Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science, 2020, 370(6520)eabd4250
[http://dx.doi.org/10.1126/science.abd4250] [PMID: 32994364]
[158]
Ziemssen, T.; Bar-Or, A.; Arnold, D.L.; Comi, G.; Hartung, H.P.; Hauser, S.L.; Lublin, F.; Selmaj, K.; Traboulsee, A.; Chin, P.; Fontoura, P.; Garren, H.; Masterman, D.; Kappos, L.P. 2 Effect of ocrelizumab on humoral immunity markers in the phase iii, double-blind, double-dummy, IFN β -1a–controlled OPERA I and OPERA II studies. Clin. Neurophysiol., 2017, 128(10), 326-327.
[159]
Thornton, J.R.; Harel, A. Negative SARS-CoV-2 antibody testing following COVID-19 infection in Two MS patients treated with ocrelizumab. Mult. Scler. Relat. Disord., 2020, 44102341
[http://dx.doi.org/10.1016/j.msard.2020.102341] [PMID: 32622338]
[160]
Fajnzylber, J.; Regan, J.; Coxen, K.; Corry, H.; Wong, C.; Rosenthal, A.; Worrall, D.; Giguel, F.; Piechocka-Trocha, A.; Atyeo, C.; Fischinger, S.; Chan, A.; Flaherty, K.T.; Hall, K.; Dougan, M.; Ryan, E.T.; Gillespie, E.; Chishti, R.; Li, Y.; Jilg, N.; Hanidziar, D.; Baron, R.M.; Baden, L.; Tsibris, A.M.; Armstrong, K.A.; Kuritzkes, D.R.; Alter, G.; Walker, B.D.; Yu, X.; Li, J.Z. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat. Commun., 2020, 11(1), 5493.
[http://dx.doi.org/10.1038/s41467-020-19057-5] [PMID: 33127906]
[161]
Quinti, I.; Lougaris, V.; Milito, C.; Cinetto, F.; Pecoraro, A.; Mezzaroma, I.; Mastroianni, C.M.; Turriziani, O.; Bondioni, M.P.; Filippini, M.; Soresina, A.; Spadaro, G.; Agostini, C.; Carsetti, R.; Plebani, A. A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia. J. Allergy Clin. Immunol., 2020, 146(1), 211-213.e4.
[http://dx.doi.org/10.1016/j.jaci.2020.04.013] [PMID: 32333914]
[162]
Weber, A.N.R.; Bittner, Z.; Liu, X.; Dang, T.M.; Radsak, M.P.; Brunner, C. Bruton’s tyrosine kinase: an emerging key player in innate immunity. Front. Immunol., 2017, 8, 1454.
[http://dx.doi.org/10.3389/fimmu.2017.01454] [PMID: 29167667]
[163]
van den Berg, D.F.; Te Velde, A.A. Severe COVID-19: NLRP3 inflammasome dysregulated. Front. Immunol., 2020, 11, 1580.
[http://dx.doi.org/10.3389/fimmu.2020.01580] [PMID: 32670297]
[164]
Gereige, J.D.; Maglione, P.J. Current understanding and recent developments in common variable immunodeficiency associated autoimmunity. Front. Immunol., 2019, 10, 2753.
[http://dx.doi.org/10.3389/fimmu.2019.02753] [PMID: 31921101]
[165]
Patuzzo, G.; Barbieri, A.; Tinazzi, E.; Veneri, D.; Argentino, G.; Moretta, F.; Puccetti, A.; Lunardi, C. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimmun. Rev., 2016, 15(9), 877-882.
[http://dx.doi.org/10.1016/j.autrev.2016.07.011] [PMID: 27392505]
[166]
Agarwal, S.; Cunningham-Rundles, C. Autoimmunity in common variable immunodeficiency. Ann. Allergy Asthma Immunol., 2019, 123(5), 454-460.
[http://dx.doi.org/10.1016/j.anai.2019.07.014] [PMID: 31349011]
[167]
Richardson, C.T.; Slack, M.A.; Dhillon, G.; Marcus, C.Z.; Barnard, J.; Palanichamy, A.; Sanz, I.; Looney, R.J.; Anolik, J.H. Failure of B cell tolerance in CVID. Front. Immunol., 2019, 10, 2881.
[http://dx.doi.org/10.3389/fimmu.2019.02881] [PMID: 31921145]
[168]
Pecoraro, A.; Crescenzi, L.; Galdiero, M.R.; Marone, G.; Rivellese, F.; Rossi, F.W.; de Paulis, A.; Genovese, A.; Spadaro, G. Immunosuppressive therapy with rituximab in common variable immunodeficiency. Clin. Mol. Allergy, 2019, 17, 9.
[http://dx.doi.org/10.1186/s12948-019-0113-3] [PMID: 31080365]
[169]
Baker, D.; Roberts, C.A.K.; Pryce, G.; Kang, A.S.; Marta, M.; Reyes, S.; Schmierer, K.; Giovannoni, G.; Amor, S. COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases. Clin. Exp. Immunol., 2020, 202(2), 149-161.
[http://dx.doi.org/10.1111/cei.13495] [PMID: 32671831]
[170]
Houot, R.; Levy, R.; Cartron, G.; Armand, P. Could anti-CD20 therapy jeopardise the efficacy of a SARS-CoV-2 vaccine? Eur. J. Cancer, 2020, 136, 4-6.
[http://dx.doi.org/10.1016/j.ejca.2020.06.017] [PMID: 32619884]
[171]
Ceronie, B.; Jacobs, B.M.; Baker, D.; Dubuisson, N.; Mao, Z.; Ammoscato, F.; Lock, H.; Longhurst, H.J.; Giovannoni, G.; Schmierer, K. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J. Neurol., 2018, 265(5), 1199-1209.
[http://dx.doi.org/10.1007/s00415-018-8830-y] [PMID: 29550884]
[172]
Comi, G.; Cook, S.; Giovannoni, G.; Rieckmann, P.; Sørensen, P.S.; Vermersch, P.; Galazka, A.; Nolting, A.; Hicking, C.; Dangond, F. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult. Scler. Relat. Disord., 2019, 29, 168-174.
[http://dx.doi.org/10.1016/j.msard.2019.01.038] [PMID: 30885375]
[173]
Giovannoni, G.; Comi, G.; Cook, S.; Rammohan, K.; Rieckmann, P.; Soelberg Sørensen, P.; Vermersch, P.; Chang, P.; Hamlett, A.; Musch, B.; Greenberg, S.J. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N. Engl. J. Med., 2010, 362(5), 416-426.
[http://dx.doi.org/10.1056/NEJMoa0902533] [PMID: 20089960]
[174]
Baker, D.; Amor, S.; Kang, A.S.; Schmierer, K.; Giovannoni, G. The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic. Mult. Scler. Relat. Disord., 2020, 43102174
[http://dx.doi.org/10.1016/j.msard.2020.102174] [PMID: 32464584]
[175]
Cook, S.; Leist, T.; Comi, G.; Montalban, X.; Giovannoni, G.; Nolting, A.; Hicking, C.; Galazka, A.; Sylvester, E. Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis. Mult. Scler. Relat. Disord., 2019, 29, 157-167.
[http://dx.doi.org/10.1016/j.msard.2018.11.021] [PMID: 30885374]
[176]
Jack, D.; Nolting, A.; Galazka, A. Favorable outcomes after COVID-19 infection in multiple sclerosis patients treated with cladribine tablets. Mult. Scler. Relat. Disord., 2020, 46102469
[http://dx.doi.org/10.1016/j.msard.2020.102469] [PMID: 32919180]
[177]
De Angelis, M.; Petracca, M.; Lanzillo, R.; Brescia Morra, V.; Moccia, M. Mild or no COVID-19 symptoms in cladribine-treated multiple sclerosis: Two cases and implications for clinical practice. Mult. Scler. Relat. Disord., 2020, 45102452
[http://dx.doi.org/10.1016/j.msard.2020.102452] [PMID: 32823148]
[178]
Dersch, R.; Wehrum, T.; Fähndrich, S.; Engelhardt, M.; Rauer, S.; Berger, B. COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment. Mult. Scler., 2020, 26(10), 1264-1266.
[http://dx.doi.org/10.1177/1352458520943783] [PMID: 32762488]
[179]
Baker, D.; Pryce, G.; Herrod, S.S.; Schmierer, K. Potential mechanisms of action related to the efficacy and safety of cladribine. Mult. Scler. Relat. Disord., 2019, 30, 176-186.
[http://dx.doi.org/10.1016/j.msard.2019.02.018] [PMID: 30785074]
[180]
Laugel, B.; Borlat, F.; Galibert, L.; Vicari, A.; Weissert, R.; Chvatchko, Y.; Bruniquel, D. Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity. J. Neuroimmunol., 2011, 240-241, 52-57.
[http://dx.doi.org/10.1016/j.jneuroim.2011.09.010] [PMID: 22035961]
[181]
Mitosek-Szewczyk, K.; Tabarkiewicz, J.; Wilczynska, B.; Lobejko, K.; Berbecki, J.; Nastaj, M.; Dworzanska, E.; Kolodziejczyk, B.; Stelmasiak, Z.; Rolinski, J. Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis. J. Neurol. Sci., 2013, 332(1-2), 35-40.
[http://dx.doi.org/10.1016/j.jns.2013.06.003] [PMID: 23835090]
[182]
Celius, E.G. Normal antibody response after COVID-19 during treatment with cladribine. Mult. Scler. Relat. Disord., 2020, 46102476
[http://dx.doi.org/10.1016/j.msard.2020.102476] [PMID: 32882501]
[183]
Lenze, E.J.; Mattar, C.; Zorumski, C.F.; Stevens, A.; Schweiger, J.; Nicol, G.E.; Miller, J.P.; Yang, L.; Yingling, M.; Avidan, M.S.; Reiersen, A.M. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial. JAMA, 2020, 324(22), 2292-2300.
[http://dx.doi.org/10.1001/jama.2020.22760] [PMID: 33180097]
[184]
Ghareghani, M.; Zibara, K.; Sadeghi, H.; Dokoohaki, S.; Sadeghi, H.; Aryanpour, R.; Ghanbari, A. Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis. Sci. Rep., 2017, 7(1), 4923.
[http://dx.doi.org/10.1038/s41598-017-04968-z] [PMID: 28687730]

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