Pandemic forward: Lessons learned and expert perspectives on multiple sclerosis care in the COVID-19 era

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious global health threat that has impacted healthcare delivery and accessibility across the globe. Individuals with chronic neuroimmunological diseases such as multiple sclerosis (MS) are of particular interest as they may be more vulnerable to infections due to treatment involving immunomodulatory disease modifying therapies (DMTs). Given the uncertainties and rapidly evolving circumstances associated with the pandemic, we aim to provide expert perspectives on pragmatic approaches to patient-centered MS care, which in recent years has shifted towards early intervention to substantively alter disease course and prevent irreversible progression. We will emphasize the need for flexible and evidence-based shared decision-making to provide holistic care for people with MS (PwMS) throughout the pandemic and beyond. The pandemic has changed the day-to-day management of MS (Mateen et al., 2020Mateen F.J. Rezaei S. Alakel N. Gazdag B. Kumar A.R. Vogel A. Impact of COVID-19 on U.S. and Canadian neurologists' therapeutic approach to multiple sclerosis: a survey of knowledge, attitudes, and practices.J. Neurol. 2020; : 1-9Google Scholar). Stay-at-home orders and social distancing measures have limited in-person interactions with MS care teams and reduced access to health facilities for diagnosis and monitoring. Pandemic-related restrictions and patient concerns of potential infection outside of the home have led to gaps in clinical care, resulting in potential delayed disease evaluation, diagnosis, and monitoring as well as care for non-MS comorbidities (Vogel et al., 2020Vogel A.C. Schmidt H. Loud S. McBurney R. Mateen F.J. Impact of the COVID-19 pandemic on the health care of >1,000 People living with multiple sclerosis: a cross-sectional study.Mult. Scler. Relat. Disord. 2020; : 46Google Scholar). Access to critical rehabilitative care such as physical, occupational, and speech therapy has also been disrupted, impacting the holistic approach to patient support. These changes to interactions with the MS care team have resulted in swift adaptations to patient care, including an increased reliance on telehealth and other services (Sullivan et al., 2020Sullivan A.B. Kane A. Roth A.J. Davis B.E. Drerup M.L. Heinberg L.J. The COVID-19 crisis: a mental health perspective and response using telemedicine.J. Patient Exp. 2020; 7: 295-301Crossref PubMed Google Scholar). Along with its clinical impacts, the COVID-19 pandemic has adversely affected the physical, emotional, and mental wellbeing of many PwMS (Motl et al., 2020Motl R. Ehde D. Shinto L. Fernhall B. LaRocca N. Zackowski K. Health behaviors, wellness, and multiple sclerosis amid COVID-19.Arch. Phys. Med. Rehabil. 2020; 101: 1839-1841Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). For instance, pandemic-related fears and stay-at-home orders may have reduced activity levels for many PwMS, which could negatively impact their physical condition and quality of life, and increase their risk of developing non-MS comorbidities (Synnott, 2020Synnott E. Bridging the gap in multiple sclerosis rehabilitation during Covid-19.J. Mult. Scler. 2020; 7: 01Google Scholar). Social distancing measures have limited in-person engagements with their social support networks, thereby potentially impacting their mental health (Bhaskar et al., 2020Bhaskar S. Bradley S. Israeli-Korn S. Menon B. Chattu V.K. Thomas P. Chawla J. Kumar R. Prandi P. Ray D. Golla S. Surya N. Yang H. Martinez S. Ozgen M.H. Codrington J. González E.M.J. Toosi M. Hariya Mohan N. Menon K.V. Chahidi A. Mederer Hengstl S. Chronic neurology in COVID-19 era: clinical considerations and recommendations from the REPROGRAM consortium.Front. Neurol. 2020; 11: 664Crossref PubMed Scopus (45) Google Scholar). Mental wellbeing may be further compromised by financial concerns stemming from self-quarantining or job loss, and heightened fears about contracting COVID-19 (Vogel et al., 2020Vogel A.C. Schmidt H. Loud S. McBurney R. Mateen F.J. Impact of the COVID-19 pandemic on the health care of >1,000 People living with multiple sclerosis: a cross-sectional study.Mult. Scler. Relat. Disord. 2020; : 46Google Scholar). It is therefore important to ensure that PwMS receive the physical and psychosocial care needed to see them safely through the pandemic (Figure 1). Fortunately, telehealth services may be leveraged to fill the gap (Sullivan et al., 2020Sullivan A.B. Kane A. Roth A.J. Davis B.E. Drerup M.L. Heinberg L.J. The COVID-19 crisis: a mental health perspective and response using telemedicine.J. Patient Exp. 2020; 7: 295-301Crossref PubMed Google Scholar) and could be an effective tool for rehabilitative and supportive MS care during the pandemic (DeLuca et al., 2020DeLuca J. Chiaravalloti N.D. Sandroff B.M. Treatment and management of cognitive dysfunction in patients with multiple sclerosis.Nat. Rev. Neurol. 2020; 16: 319-332Crossref PubMed Scopus (64) Google Scholar). Additionally, racial and social disparities in the impact of COVID-19 in the US have become evident, with underserved and ethnic minority populations being disproportionately affected (Webb Hooper et al., 2020Webb Hooper M. Nápoles A.M. Pérez-Stable E.J. COVID-19 and racial/ethnic disparities.JAMA. 2020; 323: 2466-2467Crossref PubMed Scopus (1198) Google Scholar). These disparities underscore the need to better serve PwMS in these more vulnerable populations. The current state of the evidence suggests that simply having MS does not increase risk of SARS-CoV-2 infection or worsen clinical outcomes compared to those without MS (Evangelou et al., 2020Evangelou N. Garjani A. dasNair R. Hunter R. Tuite-Dalton K.A. Craig E.M. Rodgers W.J. Coles A. Dobson R. Duddy M. Ford D.V. Hughes S. Pearson O. Middleton L.A. Rog D. Tallantyre E.C. Friede T. Middleton R.M. Nicholas R. Self-diagnosed COVID-19 in people with multiple sclerosis: a community-based cohort of the UK MS register.J. Neurol., Neurosurg; Psychiatry. 2020; (jnnp-): 2020-324449Google Scholar; Parrotta et al., 2020Parrotta 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.Neurol. - Neuroimmunol. Neuroinflamm. 2020; 7: e835Crossref PubMed Scopus (99) Google Scholar). As with the general population, PwMS with risk factors such as older age, obesity, diabetes, cardiac and pulmonary comorbidities, and potentially physical disability may be at higher risk for more severe outcomes of COVID-19 if they become infected (Louapre et al., 2020Louapre 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. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis.JAMA Neurol. 2020; Crossref PubMed Scopus (262) Google Scholar; Multiple Sclerosis International Federation 2020Multiple Sclerosis International Federation, 2020. The coronavirus and MS – updated global advice. https://www.msif.org/news/2020/02/10/the-coronavirus-and-ms-what-you-need-to-know/. (Accessed 30 September 2020).Google Scholar; Sormani et al., 2020Sormani 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. Musc-19 Study GroupDisease modifying therapies and COVID-19 severity in multiple sclerosis.Lancet. 2020; Google Scholar). PwMS are therefore advised to follow the same World Health Organization guidelines as the general population including wearing a face mask, maintaining social distancing, and practicing good hygiene (Multiple Sclerosis International Federation 2020Multiple Sclerosis International Federation, 2020. The coronavirus and MS – updated global advice. https://www.msif.org/news/2020/02/10/the-coronavirus-and-ms-what-you-need-to-know/. (Accessed 30 September 2020).Google Scholar). Those at high risk of severe COVID-19, whether they have MS or not, are advised to be extra vigilant to protect against infection (Louapre et al., 2020Louapre 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. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis.JAMA Neurol. 2020; Crossref PubMed Scopus (262) Google Scholar; Multiple Sclerosis International Federation 2020Multiple Sclerosis International Federation, 2020. The coronavirus and MS – updated global advice. https://www.msif.org/news/2020/02/10/the-coronavirus-and-ms-what-you-need-to-know/. (Accessed 30 September 2020).Google Scholar). Studies evaluating DMT use on infection severity have generally reported mixed results (Louapre et al., 2020Louapre 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. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis.JAMA Neurol. 2020; Crossref PubMed Scopus (262) Google Scholar; Sormani et al., 2020Sormani 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. Musc-19 Study GroupDisease modifying therapies and COVID-19 severity in multiple sclerosis.Lancet. 2020; Google Scholar). An initial analysis of the MS Global Data-Sharing Initiative, which included 1540 PwMS with confirmed or suspected SARS-CoV-2 infection, suggested that anti-CD20 DMTs ocrelizumab and rituximab were associated with higher frequencies of hospital admission, ICU admission, and the need for artificial ventilation compared to dimethyl fumarate and other MS DMTs. However, there did appear to be no association observed between DMTs and risk of death (Simpson-Yap et al., 2020Simpson-Yap, S., De Brouwer, E., Kalincik, T., Rijke, N., Hillert, J., Walton, C., Edan, G., Moreau, Y., Spelman, T., Geys, L., Parciak, T., Gautrais, C., Lazovski, N., Pirmani, A., Ardeshirdavani, A., Forsberg, L., Glaser, A., McBurney, R., Schmidt, H., Bergmann, A., Braune, S., Stahmann, A., Middleton, R., Salter, A., Van Der Walt, A., Rojas, J., Van Der Mei, I., Ivanov, R., Sciascia Do Olival, G., Dias, A., Magyari, M., Brum, D., Mendes, M., Alonso, R., Nicholas, R., Bauer, J., Chertcoff, A., Zabalza, A., Arrambide, G., Comi, G., Peeters, L., 2020. SS02.04 - First results of the COVID-19 in MS global data sharing initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes, 8th Joint ACTRIMS-ECTRIMS meeting. Virtual.Google Scholar). In contrast, the Covisep registry in France, which included 347 PwMS with confirmed/highly suspected COVID-19 diagnosis, found no association between exposure to DMTs and infection severity (Louapre et al., 2020Louapre 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. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis.JAMA Neurol. 2020; Crossref PubMed Scopus (262) Google Scholar). More work is needed to collect well controlled data on use of DMTs in MS and negative outcomes caused by COVID-19. However, to give general guidance, clinical experts have provided their opinions on the potential effect of DMTs used for MS on SARS-CoV-2 infection risk and in general have concluded that INFβ and glatiramer acetate “may not” increase infection risk, whereas fingolimod, siponimod, B cell-depleting therapies, alemtuzumab, and cladribine “may” do so (Korsukewitz et al., 2020Korsukewitz C. Reddel S.W. Bar-Or A. Wiendl H. Neurological immunotherapy in the era of COVID-19 - looking for consensus in the literature.Na. Rev. Neurol. 2020; 16: 493-505Crossref PubMed Scopus (42) Google Scholar; Thakolwiboon et al., 2020Thakolwiboon S. Zhao-Fleming H. Pan J. Scott J.K. Shoji E. Sohn G. Avila M. Disease-modifying therapies during the COVID-19 outbreak: a narrative review of international and national recommendations.Int. J. MS Care. 2020; 22: 151-157Crossref PubMed Scopus (17) Google Scholar). The infection risk associated with natalizumab, teriflunomide, and dimethyl fumarate is thus far unclear (Korsukewitz et al., 2020Korsukewitz C. Reddel S.W. Bar-Or A. Wiendl H. Neurological immunotherapy in the era of COVID-19 - looking for consensus in the literature.Na. Rev. Neurol. 2020; 16: 493-505Crossref PubMed Scopus (42) Google Scholar; Thakolwiboon et al., 2020Thakolwiboon S. Zhao-Fleming H. Pan J. Scott J.K. Shoji E. Sohn G. Avila M. Disease-modifying therapies during the COVID-19 outbreak: a narrative review of international and national recommendations.Int. J. MS Care. 2020; 22: 151-157Crossref PubMed Scopus (17) Google Scholar). The evidence to date provides important but early insights on the impact of SARS-CoV-2 on PwMS. However, clinical decision-making during the pandemic should balance potential COVID-19 risks and the consequences of delaying higher efficacy therapies, including unintended outcomes such as worsening disability and increased relapse rate, MRI lesions, and brain atrophy that will persist long after the COVID-19 pandemic. The risk of SARS-CoV-2 infection and the potential association between infection severity and MS and DMT use has been a particularly highly debated topic of interest since the early days of the pandemic in 2020. With very limited available data, clinical guidance published in the first few months of the pandemic was based on perceived hypothetical risks associated with the mechanism of action of the DMT drug class or general principles of immunologic mechanism of action. Although well-intentioned, such recommendations are not evidence-based and may have inadvertently created confusion and, in some cases, unnecessary changes in clinical care. Cautiously, some MS treatments have been delayed or discontinued, with some experts recommending a shift to less effective DMTs. These clinical decisions may contribute to greater physical and cognitive disability for PwMS in the future. Early data from large centralized databases/registries such as the MS Global Data-Sharing Initiative (QMENTA 2020QMENTA, 2020. MS global data-sharing initiative weekly results table. https://www.qmenta.com/covid19-patients_ms-table/. (Accessed 30 September 2020).Google Scholar) and the COViMS registry (COViMS Registry 2020COViMS RegistryThe COViMS Database Public Data Update.2020https://www.covims.org/current-dataGoogle Scholar) suggest that some of the initial fears concerning SARS-CoV-2 may have been unfounded. Future data from these sources will be important in addressing questions on long-term immunity in PwMS following SARS-CoV-2 infection and, once a COVID-19 vaccine becomes available, will provide insights into the challenges associated with immunizing those on DMTs. Based on the available evidence, treatment should be similar to that provided prior to the pandemic: individualized to each person's clinical profile, taking into account factors such as age, MS disease course, current disease activity, and comorbidities. For many PwMS, treatment may likely remain unchanged unless contrary evidence emerges. All patients, whether they have MS or not, should be educated on risk factors for more severe outcomes of COVID-19 if they become infected. Vaccinations should be discussed as an integral part of MS care, particularly in relation to how some DMTs such as anti-CD20s may impact effective immune responses to routine vaccines as well as the potential SARS-CoV-2 vaccine in the future. During patient encounters, whether virtual or in person, MS care teams should make a focused effort to address patients’ fears about the effect that their MS and DMTs may have on their infection risk and outcomes. Clinicians should educate their patients about their risks based on clinical evidence and facts, rather than on hypotheticals, to ensure an informed, evidence-based, shared decision-making approach to MS care. Additionally, MS care teams should actively engage with patients during their encounters to assess any impacts the pandemic has had on their psychosocial wellbeing and to ensure their supportive care needs are being met. It is crucial that we continue to assess, diagnose, follow-up, monitor, and treat PwMS as frequently and as carefully as we did before the pandemic. Advances in telemedicine should be leveraged for all aspects of MS care to compensate for necessary distancing requirements. Jacqueline A Nicholas has received personal compensation as a consultant or speaker for Novartis Pharmaceuticals Corporation, Alexion, Biogen, Genzyme, Genentech, EMD Serono, Bristol Myers Squibb, and Vielo Bio. She also receives consulting fees from Celgene and the Multiple Sclerosis Association of America; and receives research grants from ADAMAS, Novartis Pharmaceuticals Corporation, Biogen, and Genzyme. Robert K Shin has received personal compensation as a consultant or speaker for Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Mallinckrodt, Novartis, and Sanofi Genzyme. Enrique Alvarez has received compensation for activities such as advisory boards, lectures and consultancy with the following companies and organizations: Actelion/Janssen, Alexion, Bayer, Biogen, Celgene/BMS, EMD Serono/Merck, Genentech/Roche, Genzyme, Novartis, and TG Therapeutics and research support from: Biogen, Genentech/Roche, Novartis, TG Therapeutics, Patient-Centered Outcomes Research Initiative, National Multiple Sclerosis Society, National Institutes of Health, and Rocky Mountain MS Center. Barry Hendin has received advisory and speaking honoraria from Biogen, Genentech, Genzyme, EMD Serono, Novartis and Alexion. Kavita V Nair receives consulting fees from Novartis, BMS, Biogen, and Genentech. Fred D Lublin has received personal compensation for consulting from Biogen, EMD Serono, Novartis, Teva, Actelion/Janssen, Sanofi, Acorda, Roche/Genentech, MedImmune/Viela Bio, Receptos/Celgene, TG Therapeutics, Atara Biotherapeutics, Polpharma, Mapi Pharma, Innate Immunotherapeutics, Apitope, Orion Biotechnology, Brainstorm Cell Therapeutics, Jazz Pharmaceuticals, GW Pharma, Mylan, Immunic, Population Council, and Avotres. He has received speaker's honoraria from Sanofi; and received grants from Novartis; Actelion; Biogen; Sanofi, NMSS, NIH; and Brainstorm Cell Therapeutics. Medical writing support, including assisting authors with the development of the manuscript drafts and incorporation of comments, was provided by Grace Jeong, PhD of Alphabet Health (New York, NY), supported by Novartis Pharmaceuticals Corporation, according to Good Publication Practice guidelines (https://www.ismpp.org/gpp3). The authors received no honoraria related to the development of this publication.