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COVID-19 Vaccine Considerations for MS Healthcare Providers


The following considerations supplement our vaccine guidance for patients. They are based on questions received from clinicians and are intended to help facilitate shared decision-making conversations with your patients. These considerations will be updated as more data are available.

Read our COVID-19 Vaccine Conversation Tip Sheet for information on having discussions with your patients about decisions to vaccinate.

Given the potential serious health consequences of COVID-19 disease, working with your patients to get the vaccine may be more important than optimally timing the vaccine with their DMT. The decision of when to get the COVID-19 vaccine should include an evaluation of your patient’s risk of COVID-19, including their occupation, and the current state of their MS. If the risk of their MS worsening is equal to or outweighs their risk of COVID-19, do not alter their DMT schedule and advise they get the vaccine.  
There is no evidence that current vaccines provide any additional risk to persons with MS. While individuals with MS were not formally studied, the mechanisms of action of the mRNA vaccines and the J&J vector vaccine pose no specific biological risks to persons with autoimmune diseases. The mRNA vaccine is taken up by local muscle cells/dendritic cells, is degraded locally soon after it elicits the desired vaccine response, and does NOT infect neurons. The J&J vaccine is a non-replicating (non-live or attenuated) vaccine which is modified so that it cannot cause infection.
No clear data yet exist related to the efficacy of COVID-19 vaccines in the setting of individual MS DMTs. Our guidance is based on expert consensus and data from previous studies of other vaccines. See references from Ciotti et al., 2020, Table 2 for more literature on the effects of disease modifying therapies on vaccine immune response.
Antibody responses to common vaccinations (influenza, rabies, tetanus toxoid) are expected to be substantially attenuated—but not eliminated—by immunotherapies targeting B cells (Bar-Or et al., 2020) including ocrelizumab, ofatumumab and rituximab. Other cell-depleting immune therapies such as alemtuzumab and cladribine are expected to also attenuate antibody responses, to differing extents. With highly effective COVID-19 vaccines, it’s reasonable to believe responses to them would be at least as good as the response to other vaccines studied in MS patients on the same therapies.
There are no data on the utility of measuring COVID-19 antibody titers. Antibody tests can indicate an immune response to the vaccine, but it is not yet known whether distinguishing neutralizing antibodies from merely binding antibodies is important, or what titer is the best indicator of protection.
Limited early data indicate that memory T cell responses to the vaccines (in addition to neutralizing antibody responses generated from B cells), also have a role in developing protective immunity to SARS-Cov-2. More data are needed as this is clinically relevant for patients using B-cell depleting therapies.  
Clinicians should educate their patients on the merits of continued safety measures after getting vaccinated. Responses to the current vaccines could be less effective against some of the new coronavirus strains. It’s critically important to continue protection measures, like wearing a mask, social distancing and frequent hand washing, which may provide further protection and slow the spread of the virus. Encourage family members and other close contacts to get vaccinated as well.  
Dosing alterations are not recommended for fingolimod, siponimod, ozanimod and ponesimod. This recommendation is based on a risk/benefit analysis that possible MS rebound disease may be worse than any potential increased immune response that could occur with altering DMT dosing. See the FDA prescribing information for more details on MS worsening after stopping these treatments. Dosing alterations are not necessary for patients on beta interferons, glatiramer acetate, fumarates, natalizumab and teriflunomide.
There are data that suggest increasing the interval between infusions for some patients on ocrelizumab and rituximab may be safe and may not be associated with reemergence of MS disease activity. Waiting 6 months following an ocrelizumab or rituximab infusion allows for some B-cell reconstitution. An extended dosing interval may be acceptable in clinically and radiologically stable patients who have been on ocrelizumab or rituximab for more than a year.
An extended dosing interval is not recommended for patients who have been on ocrelizumab or rituximab for less than a year. There are some data suggesting ongoing disease activity on ocrelizumab during the first 6-9 months of treatment, which may reflect the need for several cycles of treatment to achieve the depth and breadth of B-cell depletion that most effectively limits new disease activity.
Administration of COVID-19 vaccines 12 weeks post ocrelizumab and rituximab administration could be reasonable timing and would avoid treatment delay. Serum CD19 counts might not be the best biomarker for B cell reconstitution. Based on animal data, limited reconstitution could already be occurring in the tissues prior to being appreciated in the blood, which may be relevant for vaccine response. At this time, we do not see utility in assessing serum CD19 B cell counts to determine vaccine timing.    
For patients already taking ofatumumab, there are no data to currently guide timing of the vaccine in relation to last DMT injection. Based on slow reconstitution of B cells, there may be no utility in holding doses or waiting until prior to the next dose of ofatumumab to get vaccinated.
For patients already on cladribine, limited current data does not indicate obvious differences in vaccine responses based on timing. Cladribine exhibits slower kinetics of lymphopenia compared to rapid depletion by anti-CD20 or anti-CD52. It is also slower to reach nadir compared to lymphopenia with S1PR modulators (though mechanism of lymphopenia differs: cladribine depletes, S1PR modulators sequesters). For patients who have not yet started cladribine, it is reasonable to consider initiation of DMT 2-4 weeks after vaccination. Similarly, for those due for their next course of cladribine, consider timing it 2-4 weeks after vaccination.
Check the CDC for updated guidance on prophylactic and post-vaccination use of antipyretic or analgesics.


Bar-Or A, Grove RA, Austin DJ, et al. Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study [published correction appears in Neurology. 2018 Sep 11;91(11):538]. Neurology. 2018;90(20):e1805-e1814. doi:10.1212/WNL.0000000000005516
Bar-Or A, Calkwood J, Chognot C, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology 2020;95(14):e1999-e2008.
Barun B, Gabelić T, Adamec I, Babić A, Lalić H, Batinić D, Krbot Skorić M, Habek M. Influence of delaying ocrelizumab dosing in multiple sclerosis due to COVID-19 pandemics on clinical and laboratory effectiveness. Mult Scler Relat Disord. 2020 Dec 21;48:102704. doi: 10.1016/j.msard.2020.102704. Epub ahead of print.
Baker D, Pryce G, James LK, Marta M, Schmierer K. The ocrelizumab phase II extension trial suggests the potential to improve the risk: Benefit balance in multiple sclerosis. Mult Scler Relat Disord. 2020;44:102279. doi:10.1016/j.msard.2020.102279
Maarouf A, Rico A, Boutiere C, et al. Extending rituximab dosing intervals in patients with MS during the COVID-19 pandemic and beyond?. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e825. Published 2020 Jun 25. doi:10.1212/NXI.0000000000000825

The National MS Society consulted the following individuals in the development of this guidance:

MS neurologists and experts

Nancy Sicotte, MD, FAAN—Chair, National MS Society’s National Medical Advisory Committee, Cedars-Sinai Medical Center, USA
Brenda Banwell, MD— Chair of MS International Federation International Medical and Scientific Advisory Board (IMSB) – University of Pennsylvania, USA
Amit Bar-Or, MD, FRCPC—President, International Society for Neuroimmunology - University of Pennsylvania, USA
Jorge Correale, MD-- Raul Carrea Institute for Neurological Research, FLENI, Buenos Aires, Argentina
Anne Cross, MD, FAAN—Washington University and Secretary of Board of Governors of the Consortium of MS Centers, USA
Jaime Imitola, MD, FAAN—University of Connecticut, UConn Health, USA
Dorlan Kimbrough, MD—Duke University, USA
Avindra Nath, MD—National Institutes of Health/National Institutes of Neurological Disorders and Stroke, USA
Scott Newsome, DO, MSCS, FAAN, FANA—Johns Hopkins University and President of the Board of Governors of the Consortium of MS Centers, USA
Penny Smyth, MD, FRCPC—University of Alberta, Canada
Rachael Stacom, MS, ANP-BC, MSCN—Independence Care System, USA

Staff from MS Partner Organizations

Julie Fiol, RN, MSCN—National MS Society, USA
Pamela Kanellis, PhD—MS Society of Canada
Julie Kelndorfer—MS Society of Canada
Hope Nearhood, MPH, PMP—National MS Society, USA
Leslie Ritter—National MS Society, USA


© 2021 The National Multiple Sclerosis Society is a tax exempt 501(c)3 nonprofit organization. Its Identification Number (EIN) is 13-5661935.