key: cord-0843376-suc8e0xa authors: Yamout, Bassem I; Zakaria, Magd; Inshasi, Jihad; Al-Jumah, Mohammad; Zeineddine, Maya; Dahdaleh, Maurice; Bohlega, Saeed; Gouider, Riadh; Alroughani, Raed title: MENACTRIMS Practice Guideline for COVID-19 Vaccination in Patients with Multiple Sclerosis date: 2021-08-25 journal: Mult Scler Relat Disord DOI: 10.1016/j.msard.2021.103225 sha: 7029a18a423314bf838c07b398209bb295eee9be doc_id: 843376 cord_uid: suc8e0xa Patients with multiple sclerosis (MS) should be vaccinated against COVID-19. All COVID-19 vaccines are effective and do not appear to carry any additional risk for patients with MS. Patients with MS should get a COVID-19 vaccine as soon as it becomes available. The risks of COVID-19 disease outweigh any potential risks from the vaccine. Even if vaccinated, patients with MS should continue to practice standard and recommended precautions against COVID-19, such as wearing a face mask, social distancing and washing hands. There is no evidence that patients with MS are at higher risk of complications from the mRNA, non-replicating viral vector, inactivated virus or protein COVID-19 vaccines, compared to the general population. COVID-19 Vaccines are safe to use in patients with MS treated with disease-modifying therapies (DMTs). The effectiveness of vaccination may be affected by few of the DMTs but yet some protection is still provided For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy.  COVID-19 Vaccines are safe to use in patients with MS treated with disease-modifying therapies (DMTs).  The effectiveness of vaccination may be affected by few of the DMTs but yet some protection is still provided  For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy. Keywords: COVID-19; multiple sclerosis; SARS-CoV-2; vaccines; disease-modifying therapies Multiple sclerosis (MS) is an autoimmune, demyelinating, neurodegenerative disease of the central nervous system (CNS) that might cause significant and irreversible disability 1 . Patients with MS are at increased risk for acquiring infections and disease-modifying therapies (DMTs), which suppress or modulate the immune system, have been associated with increased risk of infections [2] [3] [4] . For this reason, vaccination as the most efficient measure to prevent infections is imperative in this population. This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), causative agent of the COVID-19 disease pandemic. Several COVID-19 vaccines with various mechanisms of action and diverse immunogenic properties are currently available worldwide, authorized to varying degrees by the Food and Drug Administration (FDA), European Medicine Agency (EMA) and World Health Organization (WHO) under emergency use authorizations (EUAs), with many others in development 5 . As the COVID-19 vaccine repertoire is becoming complex, questions regarding potential interactions between the novel vaccines against COVID-19 and different DMTs are arising among MS patients and clinicians. Immunological studies have shown that the coordinated interactions between T and B lymphocytes of the adaptive immune system are essential to the successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells [6] [7] [8] [9] [10] [11] [12] . CD4 ₊ T cells facilitate CD8 ₊ T cell and B cell activation, while B cells drive and sustain T cell memory. Previous studies of conventional vaccines in MS patients have highlighted how each DMT or class of DMTs might impact the efficacy of a COVID-19 vaccine [13] [14] [15] [16] . DMTs such as interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, and natalizumab may not impair the immune response to vaccination, whereas, DMTs that rely on sequestration or depletion of T cells, B cells or both such as shingosine-1-phosphate (S1P) receptor modulators, cladribine, alemtuzumab and anti-CD20 therapies may reduce vaccine efficacy. Although robust data to support evidence-based recommendations on COVID-19 vaccinations is not yet available, this practice guideline aim is to offer guidance on vaccinating MS patients during the COVID-19 pandemic based on previous vaccine studies, mechanism of action of each DMT, currently available COVID-19 vaccine studies, and expert opinion. A group of regional experts selected by MENACTRIMS (Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis) held two consecutive meetings and several subsequent discussions to review all available evidence regarding COVID-19 vaccines in MS patients. The aim was to develop practical recommendations that would support clinical practice in the region. After reviewing all of the evidence, preliminary recommendations were developed by a subcommittee. Using the Delphi methodology through online meetings, the final version of this guideline was developed. There are several COVID-19 vaccines currently in use in different countries under EUAs, with many more currently under trial. There are currently four different types of COVID-19 vaccine in use or in development that work in different ways (Table 1 ). There is no theoretical reason or evidence from clinical trials to indicate that any of the currently available vaccines can pose any particular risk to patients with MS [24] [25] [26] .  Progressive MS, older age, higher level of disability and comorbidities (e.g., diabetes, high blood pressure, obesity, heart and lung disease, pregnancy), increase the risk for hospitalization due to COVID-19 [24] [25] [26] . Patients with MS in these high-risk groups are especially encouraged to get vaccinated as soon as vaccines becomes available.  Some DMTs 32-33 may make the vaccine less effective but it might still provide some protection.  It is important to note that most studies evaluating the effect of DMTs on vaccine efficacy, have measured serum antibodies. However T-cell mediated immunity might still be able to provide protection against infection with COVID-19 even if antibody response to the vaccine is reduced.  For certain DMTs we may consider coordinating the timing of the vaccine with the timing of the DMT dose to increase vaccine efficacy (Table 2) . For patients about to start fingolimod, siponimod or ozanimod, it is recommended to obtain full vaccination 2-4 weeks before starting treatment 34 . For patients already taking fingolimod, siponimod or ozanimod, treatment should continue as prescribed and patients can get vaccinated as soon as the vaccine is available. However, recent data has shown that patients on fingolimod have a significantly decreased humoral response to COVID-19 vaccines 35 . For patients about to start alemtuzumab, it is recommended to obtain full vaccination 4 weeks before starting treatment. For patients already taking alemtuzumab, consider starting the vaccine injections at least 6 months after the last alemtuzumab dose 36 . When possible, resume alemtuzumab at least 4 weeks after full vaccination. It is acceptable to delay the second cycle of alemtuzumab for up to 2 months to obtain full vaccination. For patients about to start cladribine, it is recommended to obtain full vaccination 2-4 weeks before starting treatment. Recent data showed that the efficacy of COVID-19 vaccines in patients on cladribine was similar to healthy controls when vaccination was initiated 4.4 months after the last dose of cladribine, even in patients with Grade III lymphopenia 35 . Other studies have also shown that patients on cladribine with Grade I or II lymphopenia mount adequate antibody response to influenza vaccines [37] [38] . However, the number of patients in those studies was small. For patients already taking cladribine, consider giving the vaccine whenever available since timing does not seem to affect vaccine efficacy. For patients due for their second course, administer cladribine 2-4 weeks after full vaccination. It is acceptable to delay the second cycle of cladribine for up to 2 months to obtain full vaccination. For patients about to start ocrelizumab or rituximab, it is recommended to obtain full vaccination 2-4 weeks before starting treatment. Recent data showed a significantly decreased response to COVID-19 and other types of vaccines in patients on ocrelizumab 35, 39 . In patients on rituximab, the ability to respond to the influenza vaccine was significantly decreased but appeared to be related to the degree of B cell recovery at the time of vaccination, which starts by 7-9 months following the last dose 40 COVID-19 vaccination is recommended for all MS patients, and currently available vaccines are safe and effective. 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All authors actively contributed to the discussion and the consensus reached. Bassem Yamout and Maya Zeineddine drafted the initial version of the manuscript and all authors discussed and reviewed the final version of the manuscript. All authors read and approved the final manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.