Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach

ABSTRACT

Background: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism’s normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. Objective: To discuss strategies to manage those patients. Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.

RESUMO

Introdução: A mais recente pandemia causada pelo coronavírus SARS-CoV-2 (COVID-19, do inglês coronavirus disease 2019) representa uma ameaça potencial para pacientes com doenças autoimunes, incluindo esclerose múltipla (EM) e transtorno do espectro de neuromielite óptica (NMOSD, do inglês neuromyelitis optica spectrum disorders). Esses pacientes são geralmente tratados com medicamentos imunomoduladores ou imunossupressores que podem alterar a resposta normal do organismo a infecções. Até o momento, não há consenso sobre como o manejo dos pacientes com EM e NMOSD deve ser realizado durante a pandemia. Objetivo: Discutir estratégias para manejar esses pacientes. Métodos: Focamos em como 1) reduzir o risco de infecção por COVID-19, como distanciamento social, telemedicina e exames laboratoriais e de imagem em intervalos mais amplos; 2) manejo de surtos, incluindo evitar tratamento de surto leve e uso de corticoide oral; 3) gerenciar terapias modificadoras de doença, como a preferência por medicamentos associados a menor risco de infecção (interferons, glatirâmer, teriflunomida e natalizumabe) e infusão em intervalo estendido de natalizumabe, quando seguro; 4) individualizar a escolha da terapia de indução para EM (anticorpos monoclonais anti-CD20, alentuzumabe e cladribina); 5) manejar terapias preventivas de NMOSD, incluindo seleção inicial de terapia e manutenção do tratamento atual; 6) manejar pacientes com EM/NMOSD que foram infectados por COVID-19. Conclusão: No futuro, séries de casos de pacientes com MS/NMOSD infectados com COVID-19 nos ajudará a definir as melhores estratégias de manejo. Por enquanto, contamos com a experiência e orientação especializadas.

Keywords:

Multiple Sclerosis - Neuromyelitis Optica Spectrum Disorders - Coronavirus - Immunosuppressive Agents - Drug Side Effects

Palavras-chave:

Esclerose Múltipla - Neuromielite Óptica - Coronavírus - Imunossupressor - Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos

Authors’ contributions:

SLPA and MFM: Substantial contributions to the study design and development, writing of the article, and critical revision. GDS, CCDD, LBF, AMBM, VAS, ABAGRG, and MB: Substantial contributions to the study design and development. DC: Substantial contributions to the approval of the final version.

Publikationsverlauf

Eingereicht: 23. Mai 2020

Angenommen: 31. Mai 2020

Artikel online veröffentlicht:
13. Juni 2023

• REFERENCES

• 1 World Health Organization. Emergencies preparedness, response. Pneumonia of unknown cause in China. WHO. 2020. Available from: <https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/>.
• 2 Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Apr;181(2):271-80.e8. https://doi.org/10.1016/j.cell.2020.02.052
• 3 Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: Properties and future directions. J Neurochem. 2008 Dec;107(6):1482-94. https://doi.org/10.1111/j.1471-4159.2008.05723.x
• 4 Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-73. https://doi.org/10.1016/S1474-4422(17)30470-2
• 5 Kennedy PM. Impact of delayed diagnosis and treatment in clinically isolated syndrome and multiple sclerosis. J Neurosci Nurs. 2013 Dec;45(6 Suppl. 1):S3-13. https://doi.org/10.1097/JNN.20200056202000560021
• 6 Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015 Jul;85(2):177-89. https://doi.org/10.1212/WNL.20200056202000561729
• 7 Lennon PVA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet. 2004 Dec;364(9451):2106-12. https://doi.org/10.1016/S0140-6736(04)17551-X
• 8 dos Passos GR, Oliveira LM, da Costa BK, Apostolos-Pereira SL, Callegaro D, Fujihara K, et al. MOG-IgG-associated optic neuritis, encephalitis, and myelitis: lessons learned from neuromyelitis optica spectrum disorder. Front Neurol. 2018 Apr;9:217. https://doi.org/10.3389/fneur.2018.00217
• 9 Papais-Alvarenga RM, Vasconcelos CCF, Carra A, Castillo ISd, Florentin S, Diaz de Bedoya FH, et al. Central nervous system idiopathic inflammatory demyelinating disorders in South Americans: a descriptive, multicenter, cross-sectional study. PLoS One. 2015 Jul;10(7):1-20. https://doi.org/10.1371/journal.pone.0127757
• 10 Carrá A, J S, Macías-Islas M. COVID-19 en pacientes con esclerosis múltiple. Recomendaciones Latinoameticanas & Sharing Initiative. Lat Am Comm Treat Res Mult Sclerosis-Lact. 2020;(1):1-22. http://www.lactrimsweb.org/wp-content/uploads/2020/04/RECOMENDAÇÇES-GERAIS-DA-AMÉRICA-LATINA-PARA-PACIENTES-E-CUIDADORES-002.pdf Acessed 11/05/2020
• 11 Pitombeira M, PaternÒ R, Braga N, Passos G, Callegaro D, Lana-Peixoto M, et al. 2º Comunicado BCTRIMS: Epidemia do Coronavírus (COVID-19) . 2020. Available from: <https://www.bctrims.org.br/wp-content/uploads/2020/03/2o-Comunicado-BCTRIMS-Epidemia-do-Coronav%C3%ADrus-COVID-19-INFORMA%C3%87%C3%95ES-AOS-PACIENTES.pdf>.
• 12 Yeroushalmi S, Maloni H, Costello K, Wallin MT. Telemedicine and multiple sclerosis: a comprehensive literature review. J Telemed Telecare. 2019 May;1357633X19840097. https://doi.org/10.1177/1357633X19840097
• 13 Enquanto EE, Batalha DA, Ao DEC, Da C. ATO ADMINISTRATIVO ( AA ) São Paulo , 17 de abril de 2020. Ref . AA Número 03 / 2020 Assunto : Teleneuroexame. 2020;(11). https://www.abneuro.org.br/post/ato-administrativo-aa-teleneuroexame. Acessed 11/05/2020
• 14 Milea D, Najjar RP, Jiang Z, Ting D, Vasseneix C, Xu X, et al. Artificial intelligence to detect papilledema from ocular fundus photographs. N Engl J Med. 2020 Apr;382:1687-95. https://doi.org/10.1056/NEJMoa1917130
• 15 Zanin L, Saraceno G, Panciani PP, Renisi G, Signorini L, Migliorati K, et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien). 2020 May:1-4. [Epub ahead of print]. https://doi.org/10.1007/s00701-020-04374-x
• 16 Beck RW, Cleary PA, Anderson MMJ, Keltner JL, Shults WT, Kaufman DI, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med. 1992 Feb;326(9):581-8. https://doi.org/10.1056/NEJM199202273260901
• 17 Lattanzi S, Cagnetti C, Danni M, Provinciali L, Silvestrini M. Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis. J Neurol. 2017 May;264(8):1697-704. https://doi.org/10.1007/s00415-017-8505-0
• 18 Le Page E, Veillard D, Laplaud DA, Hamonic S, Wardi R, Lebrun C, et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): A randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015 Sep;386(9997):974-81. https://doi.org/10.1016/S0140-6736(15)61137-0
• 19 Elovaara I, Kuusisto H, Wu X, Rinta S, Dastidar P, Reipert B. Intravenous immunoglobulins are a therapeutic option in the treatment of multiple sclerosis relapse. Clin Neuropharmacol. 2011 Mar;34(2):84-9. https://doi.org/10.1097/wnf.0b013e31820a17f3
• 20 Abboud H, Petrak A, Mealy M, Sasidharan S, Siddique L, Levy M. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016 Apr;22(2):85-192. https://doi.org/10.1177/1352458515581438
• 21 Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014 Aug;20(4):501-4. https://doi.org/10.1177/1352458513495938
• 22 Shosha E, Dubey D, Palace J, Nakashima I, Jacob A, Fujihara K, et al. Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology. 2018 Oct;91(17):E1642-51. https://doi.org/10.1212/WNL.20200056202000566392
• 23 Oliveira LM, Apóstolos-Pereira SL, Pitombeira MS, Bruel Torretta PH, Callegaro D, Sato DK. Persistent MOG-IgG positivity is a predictor of recurrence in MOG-IgG-associated optic neuritis, encephalitis and myelitis. Mult Scler. 2019 Dec;25(14):1907-14. https://doi.org/10.1177/1352458518811597
• 24 Harding K, Williams O, Willis M, Hrastelj J, Rimmer A, Joseph F, et al. Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis. JAMA Neurol. 2019 Feb;76(5):536-41. https://doi.org/10.1001/jamaneurol.2018.4905
• 25 Malpas CB, Ali Manouchehrinia A, Sharmin S, Roos I, Horakova D, Havrdova EK, et al. Early clinical markers of aggressive multiple sclerosis. medRxiv. 2019 Jan;19002063. https://doi.org/10.1101/19002063
• 26 Wijnands JMA, Zhu F, Kingwell E, Fisk JD, Evans C, Marrie RA, et al. Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study. J Neurol Neurosurg Psychiatry. 2018;89(10):1050-6. https://doi.org/10.1136/jnnp-2017-317493
• 27 Epstein DJ, Dunn J, Deresinski S. Infectious complications of multiple sclerosis therapies: Implications for screening, prophylaxis, and management. Open Forum Infect Dis. 2018 Jul;5(8):1-8. https://doi.org/10.1093/ofid/ofy174
• 28 The coronavirus and MS - global advice _ MS International Federation. https://www.msif.org/news/2020/02/10/the-coronavirus-and-ms-what-you-need-to-know/. Acessed 11/05/2020
• 29 Hughes R, Pedotti R, Koendgen H. COVID-19 in persons with multiple sclerosis treated with ocrelizumab - a pharmacovigilance case series. Mult Scler Relat Disord. 2020 May;42:102192. https://doi.org/10.1016/j.msard.2020.102192
• 30 Giovannoni G. Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19. Mult Scler Relat Disord. 2020;41:102135. https://doi.org/10.1016/j.msard.2020.102135
• 31 Hatcher SE, Waubant E, Nourbakhsh B, Crabtree-Hartman E, Graves JS. Rebound syndrome in patients with multiple sclerosis after cessation of fingolimod treatment. JAMA Neurol. 2016 Jul;73(7):790-4. https://doi.org/10.1001/jamaneurol.2016.0826
• 32 Sorensen PS, Koch-Henriksen N, Petersen T, Ravnborg M, Oturai A, Sellebjerg F. Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients. J Neurol. 2014 Apr;261(6):1170-7. https://doi.org/10.1007/s00415-014-7325-8
• 33 Weideman AM, Tapia-Maltos MA, Johnson K, Greenwood M, Bielekova B. Meta-analysis of the age-dependent efficacy of multiple sclerosis treatments. Front Neurol. 2017 Nov;8:577. https://doi.org/10.3389/fneur.2017.00577
• 34 Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaître O, Cohen P, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov;371(19):1771-80. https://doi.org/10.1056/NEJMoa1404231
• 35 Durozard P, Rico A, Boutiere C, Maarouf A, Lacroix R, Cointe S, et al. Comparison of the response to rituximab between myelin oligodendrocyte glycoprotein and aquaporin-4 antibody diseases. Ann Neurol. 2020 Feb;87(2):256-66. https://doi.org/10.1002/ana.25648
• 36 Warny M, Helby J, Nordestgaard BG, Birgens H, Bojesen SE. Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. PLoS Med. 2018 Nov;15(11):1-22. https://doi.org/10.1371/journal.pmed.1002685
• 37 Kappos L, Radue E-W, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb;362(5):387-401. https://doi.org/10.1056/NEJMoa0909494
• 38 Francis G, Kappos L, O’Connor P, Collins W, Tang D, Mercier F, et al. Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy. Mult Scler. 2014 Apr;20(4):471-80. https://doi.org/10.1177/1352458513500551
• 39 Comi G, Miller AE, Benamor M, Truffinet P, Poole EM, Freedman MS. Characterizing lymphocyte counts and infection rates with long-term teriflunomide treatment: pooled analysis of clinical trials. Mult Scler. 2019 Jun:1352458519851981. https://doi.org/10.1177/1352458519851981
• 40 Bomprezzi R. Dimethyl fumarate in the treatment of relapsing-remitting multiple sclerosis: An overview. Ther Adv Neurol Disord. 2015 Jan;8(1):20-30. https://doi.org/10.1177/1756285614564152
• 41 Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol. 2020 Oct;77(2):184-91. https://doi.org/10.1001/jamaneurol.2019.3365
• 42 Foley J, Carrillo-Infante C, Smith J, Evans K, Ho P-R, Lee L, et al. The 5-year Tysabri global observational program in safety (TYGRIS) study confirms the long-term safety profile of natalizumab treatment in multiple sclerosis. Mult Scler Relat Disord. 2020 Apr;39:101863. https://doi.org/10.1016/j.msard.2019.101863
• 43 Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, et al. Extended interval dosing of natalizumab in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):885-9. https://doi.org/10.1136/jnnp-2015-312940
• 44 Zhovtis Ryerson L, Foley J, Chang I, Kister I, Cutter G, Metzger RR, et al. Risk of natalizumab-associated PML in patients with MS is reduced with extended interval dosing. Neurology. 2019 Oct;93(15):e1452-62. https://doi.org/10.1212/WNL.20200056202000568243
• 45 Barmettler S, Ong MS, Farmer JR, Choi H, Walter J. Association of immunoglobulin levels, infectious risk, and mortality with rituximab and hypogammaglobulinemia. JAMA Netw Open. 2018 Nov;1(7):e184169. https://doi.org/10.1001/jamanetworkopen.2018.4169
• 46 Ellrichmann G, Bolz J, Peschke M, Duscha A, Hellwig K, Lee D-H, et al. Peripheral CD19 + B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders. J Neurol. 2019 Jan;266(1):57-67. https://doi.org/10.1007/s00415-018-9092-4
• 47 Sormani MP, Study I. An Italian programme for COVID-19 infection in multiple sclerosis. Lancet Neurol. 2020 Jun;19(6):481-2. https://doi.org/10.1016/S1474-4422(20)30147-2
• 48 Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Sørensen PS, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010 Feb;362(5):416-26. https://doi.org/10.1056/NEJMoa0902533
• 49 Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol NeuroInflamm. 2017 Jul;4(4). https://doi.org/10.1212/NXI.20200056202000560360
• 50 Kocsik AS, Klein DE, Liedke M, Kaunzner UW, Nealon NM, Gauthier SA, et al. Induction of disease remission with one cycle of alemtuzumab in relapsing-remitting MS. J Neurol. 2018 Apr;265(5):1226-9. https://doi.org/10.1007/s00415-018-8845-4
• 51 Kim SH, Huh SY, Lee SJ, Joung AR, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep;70(9):1110-7. https://doi.org/10.1001/jamaneurol.2013.3071
• 52 Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroid use. Rheum Dis Clin North Am. 2016 Feb;42(1):157-76. https://doi.org/10.1016/j.rdc.2015.08.004
• 53 Singh G, Fries JF, Spitz P, Williams CA. Toxic effects of azathioprine in rheumatoid arthritis. A national post-marketing perspective. Arthritis Rheum. 1989 Jul;32(7):837-43.
• 54 Pollak R, Nishikawa RA, Mozes MF, Jonasson O. Azathioprine-induced leukopenia - clinical significance in renal transplantation. J Surg Res. 1980 Sep;29(3):258-64. https://doi.org/10.1016/0022-4804(80)90169-9
• 55 Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M. Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol. 2014 Mar;71(3):324-30. https://doi.org/10.1001/jamaneurol.2013.5699
• 56 Subedi A, Magder LS, Petri M. Effect of mycophenolate mofetil on the white blood cell count and the frequency of infection in systemic lupus erythematosus. Rheumatol Int. 2015 Oct;35(10):1687-92. https://doi.org/10.1007/s00296-015-3265-6
• 57 Nogueras F, Espinosa MD, Mansilla A, Torres JT, Cabrera MA, Martín-Vivaldi R. Mycophenolate mofetil-induced neutropenia in liver transplantation. Transplant Proc. 2005 Apr;37(3):1509-11. https://doi.org/10.1016/j.transproceed.2005.02.038
• 58 Cronstein BN. Molecular therapeutics: Methotrexate and its mechanism of action. Arthritis Rheum. 1996 Dec;39(12):1951-60. https://doi.org/10.1002/art.1780391203
• 59 Berkowitz RS, Goldstein DP, Bernstein MR. Ten years’ experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease. Gynecol Oncol. 1986 Jan;23(1):111-8. https://doi.org/10.1016/0090-8258(86)90123-X
• 60 Gutierrez-Ureña S, Molina JF, García CO, Cuéllar ML, Espinoza LR. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum. 1996 Feb;39(2):272-6. https://doi.org/10.1002/art.1780390214
• 61 Saag KG, Gim GT, Patkar NM, Anuntiyo J, Finney C, Curtis JR, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthrit Care Res. 2008 Jun;59(6):762-84. https://doi.org/10.1002/art.23721
• 62 Neurologia AB de. REDONE - PROJETO COVID19. https://www.abneuro.org.br/redone-projeto-covid-19.. Acessed 11/05/2020
• 63 Farez MF, Correale J, Armstrong MJ, Rae-Grant A, Gloss D, Donley D, et al. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2019 Sep;93(13):584-94. https://doi.org/10.1212/WNL.20200056202000568157
• 64 Child R, Schedule AI. 2020 4. 2020. https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html Acessed 11/05/2020
• 65 SBIm. CALENDÁRIO DE VACINAÇÃO PACIENTES ESPECIAIS. https://sbim.org.br/images/calendarios/calend-sbim-pacientes-especiais.pdf Acessed 11/05/2020
• 66 Vacinas DAS. CALENDÁRIO DE VACINAÇÃO SBIm ADULTO. 2021:2021. https://sbim.org.br/images/calendarios/calend-sbim-adulto.pdf. Acessed 11/05/2020
• 67 Lopez A, Mariette X, Bachelez H, Belotd A, Bonnottee B, Hachulla E, et al. Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis. J Autoimmun. 2017 Jun;80:10-27. https://doi.org/10.1016/j.jaut.2017.03.011
• 68 Rákóczi E, Szekanecz Z. Pneumococcal vaccination in autoimmune rheumatic diseases. RMD Open. 2017;3(2):e000484. https://doi.org/10.1136/rmdopen-2017-000484
• 69 Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv. 2020 Feb;2020.02.22.20026500. https://doi.org/10.1101/2020.02.22.20026500
• 70 Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S. Acute myelitis after SARS-CoV-2 infection: a case report. medRxiv. 2020 Jan:2020.03.16.20035105. https://doi.org/10.1101/2020.03.16.20035105
• 71 Munhoz RP, Pedroso JL, Nascimento FA, Almeida SM, Barsottini OGP, Cardoso FEC, et al. Neurological complications in patients with SARS-CoV-2 infection: a systematic review. Arq Neuro-Psiquiatr. 2020 May Jun;78(5): 290-300. http://dx.doi.org/10.1590/0004-282x20200051
• 72 Liu Y, Yan L-M, Wan L, Xiang T-X, Le A, Liu J-M, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis. 2020 May;20(6):656-7. https://doi.org/10.1016/S1473-3099(20)30232-2
• 73 Brownlee W, Bourdette D, Broadley S, Killestein J, Ciccarelli O. Treating multiple sclerosis and neuromyelitis optica spectrum disorder during the COVID-19 pandemic. Neurology. 2020 Jun;92(22):10.1212/WNL.20200056202000569507. https://doi.org/10.1212/wnl.20200056202000569507