To Vaccinate or Not to Vaccinate? That’s the Question for MS and COVID-19

COVID-19 and MS

As numerous foreign studies and data from the Czech Republic have shown, the course of COVID-19 in MS patients is generally similar to the rest of the population. Risk factors include certain comorbidities (especially cardiovascular ones), a higher body mass index (BMI), and older age. However, there are risk factors specific to MS patients [1, 2]. Those at higher risk of severe COVID-19 are:

• patients undergoing therapy targeting the CD20 molecule on the surface of B lymphocytes;
• patients who have received a pulse of corticosteroids in the past 2 months;
• patients with a higher degree of neurological disability.

Beyond the risk of a severe course of COVID-19, MS patients inherently face another risk – relapse. According to a Czech (and the most extensive to date) study [3] based on data from 495 patients, approximately 7.3% experienced a relapse within 3 months after contracting COVID-19. This represents an increase compared to the previous year in the same patients.

Safety profile of vaccination in MS patients

One of the most effective measures against COVID-19 has proven to be vaccination. However, for patients with autoimmune diseases, vaccination has its specifics – especially the potential risk of exacerbating the primary disease. This issue was also analyzed using data from Czech patients. In the 3 months following the first dose of vaccination, glucocorticoids had to be administered due to an attack in 5.3% of the total 1661 vaccinated patients. Compared to the incidence of relapses in the same patients in the previous year (about 4%), this is a significant yet fortunately mild and clinically not very significant increase [3]. It shows that vaccination in MS patients is not entirely without risks and should be prescribed with caution, not indiscriminately.

The above data also raise the question of risk factors for relapse after vaccination. In this regard, we are somewhat fortunate. The least risk of relapse is seen in older patients with a long duration of the disease – those who are at the highest risk of a severe course of COVID-19. For them, vaccination is unequivocally indicated.

Safe, yes, but what about efficacy?

Besides safety, the efficacy of vaccination is, of course, also very important. Many studies [4–7] have indirectly tried to evaluate this through antibody and cellular immunity analysis – especially considering the specific type of disease-modifying drug (DMD). For most DMDs, there is no impact on the response.

Unfortunately, antibody immunity is reduced in patients on therapy targeting the CD20 molecule (who are also at risk for a severe course) and those on oral DMDs – S1P modulators. For patients treated with these agents, cellular immunity often does not develop either, unlike with anti-CD20 therapy. However, this is not a rule. In a small to low percentage of cases, antibody or cellular immune responses may occur.

Another DMD with an oral form of administration is teriflunomide, which inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, thus blocking de novo pyrimidine synthesis. This inhibits the proliferation of autoaggressive activated T and B lymphocytes without affecting resting and slow-dividing lymphocytes, which can continue to provide immune surveillance. For teriflunomide, the course of COVID-19 and the vaccination response are not affected according to reasonably extensive available data [8].

Individual approach

But how to proceed with a specific patient? An individual approach is especially important. When recommending vaccination, risk factors for a severe course (age, comorbidities, type of DMD) and relapse risk factors (age), disease activity, and response to previous vaccinations must be considered. An important factor is also the history of the infection and the time interval since this event, as well as the potential effect of vaccination. For high-risk groups, prophylactic administration of monoclonal antibodies can be considered, and in the event of COVID-19 infection, antiviral drugs can be administered.

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Sources:
1. Šťastná D., Menkyová I., Drahota J. et al. Multiple sclerosis, neuromyelitis optica spectrum disorder and COVID-19: a pandemic year in Czechia. Mult Scler Relat Disord 2021 Sep; 54: 103104, doi: 10.1016/j.msard.2021.103104.
2. Prosperini L., Tortorella C., Haggiag S. et al. Increased risk of death from COVID-19 in multiple sclerosis: a pooled analysis of observational studies. J Neurol 2022 Mar; 269 (3): 1114−1120, doi: 10.1007/s00415-021-10803-3.
3. Šťastná D., Menkyová I., Drahota J. et al. To be or not to be vaccinated: the risk of MS or NMOSD relapse after COVID-19 vaccination and infection. Mult Scler Relat Disord 2022 Sep; 65: 104014, doi: 10.1016/j.msard.2022.104014.
4. Achiron A., Mandel M., Dreyer-Alster S. et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord 2021 Apr 22; 14: 17562864211012835, doi: 10.1177/17562864211012835.
5. Achiron A., Mandel M., Gurevich M. et al. Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod. J Neurol 2022 May; 269 (5): 2286−2292, doi: 10.1007/s00415-022-11030-0.
6. Milo R., Staun-Ram E., Karussis D. et al.; Israeli Neuroimmunology Study Group on COVID-19 Vaccination in Multiple Sclerosis. Humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis: an Israeli multi-center experience following 3 vaccine doses. Front Immunol 2022 Apr 1; 13: 868915, doi: 10.3389/fimmu.2022.868915.
7. Tallantyre E. C., Scurr M. J., Vickaryous N. et al. Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis. Mult Scler Relat Disord 2022 Aug; 64: 103937, doi: 10.1016/j.msard.2022.103937.
8. Tornatore C., Wiendl H., Lublin A. L. et al. Vaccine response in patients with multiple sclerosis receiving teriflunomide. Front Neurol 2022 Feb 28; 13: 828616, doi: 10.3389/fneur.2022.828616.