Skip to main content

[{id=146030, label=Demyelinating diseases of the central nervous system (G35-G37), uri=g35-g37}, {id=145852, label=ICD, uri=icd}, {id=147619, label=Multiple sclerosis, uri=g35-g37_g35}]

g35-g37, icd, g35-g37_g35,
Intended for healthcare professionals
Skip to main content
Open access
Research article
First published online April 22, 2021

Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Anat Achiron https://orcid.org/0000-0002-2020-3126 [email protected], Mathilda Mandel, […], Sapir Dreyer-Alster, Gil Harari, David Magalashvili, Polina Sonis, Mark Dolev, Shay Menascu, Shlomo Flechter, Rina Falb, and Michael Gurevich+8View all authors and affiliations
All Articles
https://doi.org/10.1177/17562864211012835

Abstract

Background and Aims:

The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. We aimed to characterize humoral immunity in mRNA-COVID-19 MS vaccinees treated with high-efficacy DMTs.

Methods:

We measured SARS-CoV-2 IgG response using anti-spike protein-based serology (EUROIMMUN) in 125 MS patients vaccinated with BNT162b2-COVID-19 vaccine 1 month after the second dose. Patients were either untreated or under treatment with fingolimod, cladribine, or ocrelizumab. A group of healthy subjects similarly vaccinated served as control. The percent of subjects that developed protective antibodies, the titer, and the time from the last dosing were evaluated.

Results:

Protective humoral immunity of 97.9%, 100%, 100%, 22.7%, and 3.8%, was observed in COVID-19 vaccinated healthy subjects (N = 47), untreated MS patients (N = 32), and MS patients treated with cladribine (N = 23), ocrelizumab (N = 44), and fingolimod (N = 26), respectively. SARS-CoV-2 IgG antibody titer was high in healthy subjects, untreated MS patients, and MS patients under cladribine treatment, within 29.5–55 days after the second vaccine dose. Only 22.7% of patients treated with ocrelizumab developed humoral IgG response irrespective to normal absolute lymphocyte count. Most fingolimod-treated MS patients had very low lymphocyte count and failed to develop SARS-COV-2 antibodies. Age, disease duration, and time from the last dosing did not affect humoral response to COVID-19 vaccination.

Conclusions:

Cladribine treatment does not impair humoral response to COVID-19 vaccination. We recommend postponing ocrelizumab treatment in MS patients willing to be vaccinated as a protective humoral response can be expected only in some. We do not recommend vaccinating MS patients treated with fingolimod as a protective humoral response is not expected.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused a devastating disease with high rates of morbidity and mortality spreading all over the world.1
The most effective and safe way to protect people from contagious diseases is by vaccination. The lipid nanoparticle-formulated Pfizer–BioNTech COVID-19 (BNT162b2) vaccine is a new type of vaccine, based on nucleoside-modified mRNA vector vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2. This vaccine proved safe and highly efficient against COVID-19 in a large cohort of patients,2 and is currently administered all over the world.
We have vaccinated a large cohort of 555 patients with multiple sclerosis (MS) and demonstrated that the vaccine is safe for patients.3 MS patients had similar rates of adverse reactions to what has been reported in the general population, and we did not observe post-vaccination MS worsening or an immediate increase in the rate of acute relapses. Our findings support the recommendation to MS patients not to delay vaccination during the still-expanding SARS-CoV-2 pandemic.
Although we did not find differences in the adverse events profile between untreated MS patients and patients treated with disease-modifying therapies (DMTs), data related to the ability of MS patients to elicit a protective post-COVID-19 vaccination immune response under high-efficacy DMTs are crucial.
It is well known that high-efficacy DMTs induce immunomodulation associated with lymphocyte depletion involving T cells, B cells, or both.4,5 Ocrelizumab is an anti-CD20 monoclonal antibody that depletes B lymphocytes and thereby may interfere in the process of antibody production.6 Fingolimod acts as an antagonist of sphingosine-1-phosphate receptor and therefore prevents lymphocyte egression from secondary lymphoid tissues and marked peripheral blood lymphopenia.7 Cladribine is a purine analog that targets B cells more than T cells and has been shown to induce long-term selective suppression of certain subtypes of B cells, especially memory B cells.8,9
Currently, there are no data regarding the efficacy of the COVID-19 vaccine to induce humoral immunity in MS patients treated with these DMTs.
In the current study, we evaluated the humoral response to the BNT162b2-COVID-19 vaccine in adult MS patients to provide evidence-based guidelines to the MS community regarding the magnitude of protective immunity particularly in patients treated with high-efficacy DMTs.

Methods

Study participants and study design

We established guideline recommendations for COVID-19 vaccination for MS patients.3 Briefly, these guideline recommendations for COVID-19 vaccination were to promote vaccination and pre-vaccination lymphocyte count for all MS patients. Patients were recommended to be vaccinated regardless of the lymphocyte count and without stopping their current immunomodulatory treatment; specifically, patients treated with B-cell depletion therapies such as alemtuzumab or ocrelizumab and patients treated with cladribine were recommended to be vaccinated at least 3 months after the last treatment dose. We included in the current observational cohort study MS patients that performed pre-vaccination lymphocyte count and received the full COVID-19 vaccination paradigm. Blood samples were evaluated for the presence of SARS-CoV-2 IgG antibodies 1 month after the second vaccine dose. A group of healthy subjects similarly vaccinated against COVID-19 served as control.

COVID-19 vaccination

Subjects received two intramuscular injections, 21 days apart, delivered in the deltoid muscle. Each injection contained 30 µg of BNT162b2 (0.3 ml volume per dose).

Detection of SARS-CoV-2 IgG antibodies

Immunoassay for the detection of SARS-CoV-2 IgG antibodies in blood samples was performed using EUROIMMUN (EI, Lubeck, Germany) anti-SARS-CoV-2 IgG quantitative ELISA kit based on a recombinant S1 subunit of the SARS-CoV-2 spike protein. The assay was performed following the manufacturer’s instructions,10 using the AGILITY® automated ELISA analyzer (DYNEX Technologies Inc., Chantilly, VA), 1 month following COVID-19 s vaccine dose. An index value higher than 1.1 was considered positive.

Ethics and data collection

The study was approved by Sheba Medical Center Institutional Review Board (Sheba.SMC - 5596-08), and the need for informed consent was waived. Each patient record was coded anonymously to ensure confidentiality during statistical analyses.

Statistical analysis

Categorical variables are described as frequency, and percentage and continuous variables were reported by their median and interquartile range. Data were compared between the healthy subjects group and the untreated MS group, and between each DMT group and untreated MS group. Fisher’s exact test was applied to test the statistical significance of the difference in categorical variables between the study groups. An analysis of variance (ANOVA) model was applied to test the differences in SARS-CoV-2 IgG antibody titers between groups adjusted to suspected confounders. P-value cutoffs of 0.05 indicated significance. Data analyses were performed using Python (version 3.0) and SAS® (version 9.4 SAS Institute, Cary, NC).

Results

MS vaccinees

The demographic and clinical variables of the 172 study participants are presented in Table 1. We assessed 47 healthy vaccinees and 125 COVID-19 MS vaccinees comprised 72 (57.6%) females and 53 (42.4%) males; there were 76 (60.8%) relapsing-remitting, 24 (19.2%) primary-progressive, 18 (14.4%) secondary-progressive, 4 (3.2%) clinically isolated syndrome, and 3 (2.4%) radiologically isolated syndrome patients.
Table 1. Clinical and demographic variables of patients with multiple sclerosis that received COVID-19 vaccination under high-efficacy DMTs.
Study populationMS patients N = 125Healthy subjects N = 47
Cladribine N = 23Fingolimod N = 26Ocrelizumab N = 44Untreated N = 32
Follow-up after second vaccine, days
 Median3339.53746.544
 25–75 IQR29.5–35.533.2–51.532–42.235–5534.5–50
Gender, n (%)
 Females17 (73.9)12 (46.2)20 (45.5)23 (71.9)30 (63.8)
 Males6 (26.1)14 (53.8)24 (54.5)9 (28.1)17 (36.1)
Age, years
 Median43.144.953.250.554.3
 25–75 IQR36.3–47.941.3–52.046.4–61.737.1–58.943.1–61.9
Disease duration, years
 Median11.015.713.412.5___
 25–75 IQR6.8–21.88.3–20.75.5–20.26.6–18.8 
Disability by EDSS
 Median3.02.05.52.0___
 25–75 IQR1.3–4.71.1–3.44.0–6.01.0–5.3 
Time from last Tx dose to vaccination, months
 Median7.1NA4.9______
 25–75 IQR6.1–9.4 4.1–5.3  
Patients with positive SARS-CoV-19 IgG
N, (%)23 (100)1 (3.8)10 (22.7)32 (100)46 (97.9)
SARS-CoV-2 IgG titer
 Median7.00.270.298.17.4
 25–75 IQR6.5–8.10.12–0.450.06–0.897.5–8.46.4–8.1
Absolute lymphocyte count
 Median90055519401870 
 25–75 IQR630–1305402–7221395–23701650–2310 
DMTs, disease-modifying therapies; IQR, Interquartile range; EDSS, Expanded Disability Status Scale

SARS-CoV-2 anti-spike IgG

Protective humoral immunity was demonstrated in 46/47 (97.9%) of healthy subjects and all untreated MS patients. Similarly, all MS patients under cladribine treatment developed a high level of antibodies post-COVID-19 vaccination (p = 0.99).
MS patients treated with fingolimod failed to develop a post-vaccination humoral response, and only 1/26 (3.8%) had an antibody response that, although attenuated, was above the cut-off value for a positive response (p < 0.0001).
Most patients under treatment with ocrelizumab failed to develop a post-vaccination humoral response, and only 10/44 (22.7%) demonstrated a protective antibody titer (p < 0.0001).

Lymphocyte count

Absolute lymphocyte count presented as three gradings (>1000 cells/mm3, between 500 and 1000 cells/mm3, and <500 cells/mm3) in relation with post-vaccination SARS-CoV-2 IgG antibody titer by DMT treatment, is presented in Figure 1. The failure to develop SARS-CoV-2 IgG antibody response in fingolimod-treated MS patients could be related to the very low lymphocyte count in the majority of patients; 10/26 (38.5%) had a lymphocyte count below 500 cells/mm3, and an additional 13/26 (50%) had lymphocyte count between 500 and 1000 cells/mm3. Only one patient treated with Fingolimod (3.8%) showed a humoral response, but even in this subject, the SARS-CoV-2 titer was at the low protective level. This patient had a lymphocyte count of 700 cells/mm3, while three patients (11.5%) with rates >1000 cells/mm3 (see Figure 1) did not mount an immune response.
Figure 1. Post-vaccination SARS-CoV-2 IgG antibody titer by disease-modifying treatment in relation to absolute lymphocyte count presented as grading >1000 cells/mm3 (green circles), between 500 and 1000/cells mm3 (red), and <500 cells/mm3 (blue).
In ocrelizumab-treated MS patients, the failure to develop a humoral response to COVID-19 vaccine was not related to the absolute lymphocyte count as it occurred while 42/44 (95.5%) of patients had lymphocyte counts above 1000 cells/mm3.

Time from last DMT dose

For MS patients under treatment with cladribine or ocrelizumab, we specifically evaluated the time from the last treatment dose to the time of COVID-19 vaccination. The results are presented in Figure 2. All patients treated with cladribine were efficiently vaccinated and developed a protective SARS-CoV-2 antibody titer being vaccinated as early as 4.4 months after the last treatment dose. However, for MS patients treated with ocrelizumab, the relation between the last treatment dose and an effective post-vaccination humoral response demonstrated that the majority 34/44 (77.3%) of patients did not develop a protective SARS-CoV-2 antibody titer when vaccinated up to 8.9 months after the last treatment dose. Those that did develop protective antibody response were vaccinated between 3.7 and 6.4 months after the last treatment dose.
Figure 2. Time in months from last treatment dose to COVID-19 vaccination for patients with multiple sclerosis treated with cladribine or ocrelizumab in relation to post-vaccination SARS-CoV-2 IgG.
Positive post-vaccination SARS-CoV-2 IgG antibody titer is presented by a green circle; negative post-vaccination SARS-CoV-2 IgG antibody titer is presented by a red circle.

Variables affecting humoral response to COVID-19 vaccine

ANOVA model analysis of SARS-CoV-2 antibody titer by DMT adjusted for age, time from the last dose to COVID-19 vaccination, and lymphocyte count, demonstrated a significant effect of time from last treatment dose to vaccination for MS patients treated with cladribine (p = 0.0211) and for ocrelizumab (p = 0.0361). No effect on the humoral IgG response to the COVID-19 vaccine was demonstrated for age or lymphocyte count for cladribine, ocrelizumab, or fingolimod. Compared with the other DMTs groups, ocrelizumab-treated patients had higher neurological disability by the Expanded Disability Status Scale score and 23/44 (52.2%) had a primary-progressive disease course, whereas fingolimod-treated patients had longer disease duration. These differences did not significantly affect the COVID-19 vaccine humoral response.

Discussion

Vaccination against the SARS-CoV-2 pandemic is currently ongoing in large populations all over the world, and among them, many MS patients are being vaccinated. It was suggested that MS patients under DMTs might show reduced humoral response to the vaccine.11 Our study provides first-ever real-world data on the efficacy for MS patients to develop protective humoral response following Pfizer-BNT162b2-COVID-19 vaccination. Specifically, we compared the induction of immune responses between healthy vaccinees, untreated MS vaccines, and MS vaccinees treated with high-efficacy DMTs, within 4.5–6.5 weeks following the second vaccine dose, by measuring SARS-CoV-2 IgG antibodies.
It is well known that antibody levels correlate with protection against many viruses including SARS-CoV-2, and recent data suggest that high neutralizing titers are particularly important for protection against the novel SARS-CoV-2 causing the COVID-19 pandemic.12,13 In the current study we used the Euroimmune ELISA assay to quantify SARS-CoV-2 antibody level as it was reported to highly correlate with the neutralizing antibody assay.14
Our findings demonstrated that untreated COVID-19-vaccinated MS patients developed protective SARS-CoV-2 humoral responses similarly to healthy vaccinees, and similarly to the findings recently reported in the literature for non-MS vaccinees.15
However, for MS patients treated with high-efficacy DMTs, the immune response to COVID-19 vaccination varied.
All cladribine-treated MS patients demonstrated a protective humoral immune response to the COVID-19 vaccine. SARS-CoV-2 antibody response was already evident within 4.4 months after the last treatment dose, and the SARS-CoV-2 antibody titer did not differ from that of untreated MS patients and healthy subjects. These encouraging findings suggest that cladribine treatment does not prevent the induction of appropriate post-COVID-19 vaccination response, similar to what has been reported for cladribine-treated patients that were vaccinated against seasonal influenza and varicella-zoster.16,17
Post-COVID-19 vaccination humoral responses were impaired in MS patients treated with ocrelizumab or with fingolimod. The majority of vaccinated patients these medications failed to show a protective level of SARS-CoV-2 spike-specific IgG following COVID-19 vaccination protocol.
For ocrelizumab-treated patients, the failure to mount appropriate IgG immune response was regardless of the absolute lymphocyte counts that were in the normal range, or to the time-interval from the last ocrelizumab treatment dose that was from 3.1 to 8.9 months, suggesting the need to postpone the next dosing to enable an effective post-vaccination humoral response.
For fingolimod-treated COVID-19-vaccinated MS patients, the low absolute lymphocyte count in the majority of patients—88.5% had a lymphocyte count less than 1000 cells/mm3—may be the cause for failing to mount an immune response. Moreover, even in the small group of 11.5% fingolimod-treated MS patients with an absolute lymphocyte count >1000 cells/mm3, no humoral response was detected. This concerning finding suggests that a decrease in CD19+ B cells occurs irrespective of the degree of lymphopenia as was previously described.18
It is well described that MS patients treated with ocrelizumab or fingolimod not only have higher rates of morbidity due to viral infections,19 but also respond less to vaccinations. Immunizing patients against influenza using the inactivated virus vaccine and the toxoid tetanus resulted in decreased vaccination-induced immune responses,20,21 mainly due to a decline in humoral immunity. Similarly, the consequence of immunosenescence resulted in reduced adaptive immune responses to COVID-19 vaccination.
Our findings raise two major questions related to the induction of humoral responses following COVID-19 vaccination in MS patients under treatment with fingolimod or ocrelizumab.
It is not surprising that in the presence of low lymphocyte counts, as occurs in MS patients treated with fingolimod where lymphocytes are reduced by number in the peripheral blood and segregated in secondary lymphoid tissues, a failure to mount an appropriate humoral response happens. Therefore, the relevant question is related to the need to stop or switch fingolimod treatment for the purpose of re-populating the peripheral blood and with time enable patients to appropriately be vaccinated.
The second intriguing question is why ocrelizumab-treated MS patients, despite normal lymphocyte counts, fail to develop an anti-SARS-CoV-2 humoral response, even many months after the last dosing. We suggest that this failure is related to depletion of naive and memory B lymphocytes that occurs under ocrelizumab treatement.22 These cells are responsible for the generation of antibody production, and therefore their depletion harms humoral protection.
The limitations of our study are that although it presents the first data on the efficacy of COVID-19 vaccinations in patients with MS treated with high-efficacy DMTs, the total number of vaccinated patients in each medication group is rather low. This is because of the acuity of the situation but limits the impact of the outcome, even though statistical analyses were strongly positive. Another limitation of the study is that vaccine-specific memory T- or B-cell responses were not assessed. This is of importance especially in MS patients that did not develop humoral immunity, as the absence of specific S1 spike antibodies does not necessarily mean an absence of adaptive immune response.
Our study presents the worldwide first comprehensive data on humoral COVID-19 vaccination response in patients with MS treated with high-efficacy DMTs.
In practice, following the findings of our study, we have updated our COVID-19 vaccination guideline recommendations for patients with MS. We recommend the policy of vaccinating untreated MS patients without any limitations and vaccinating cladribine-treated MS patients at least 4.4 months after the last dosing. For MS patients treated with fingolimod, we currently do not promote COVID-19 vaccination unless their lymphocyte count is above 1000 cells/mm3. In the small percentage of fingolimod-treated patients with higher lymphocyte counts, caution is recommended as the level of lymphocytes did not confirm a correlation with a protective humoral response.
Patients treated with ocrelizumab that are at especially high risk for severe disease and death from COVID-1923 are recommended to postpone their upcoming treatment and be vaccinated at least 9 months after the last dosing.
It is of note that fingolimod and ocrelizumab unvaccinated MS patients might be at risk either for getting infected with SARS-CoV-2 virus while being vaccination-paused or by experiencing rebound disease activity while being switched to another DMT. However, as there are countries with a shortage of COVID-19 vaccinations, our findings are of importance for health decisions for appropriately prioritizing the management of MS patients that will best benefit from COVID-19 vaccination.
Future studies are needed to further evaluate the longevity of humoral response following COVID-19 vaccination in MS patients and to further elucidate B-cell and T-cell memory responses in the DMTs-treated MS population.

Acknowledgments

We thank our nurse team at the Sheba Multiple Sclerosis Center, Mrs. Raz Havi, Mrs. Zileznick Ilana, Mrs. Galami Rivka, and Mrs. Sabag Anat for their dedicated work and devoted care of patients. We thank Ms. Shany Tomer and Mrs. Yamit Titngi for their outstanding technical assistance.

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

References

1. Seyed Hosseini E, Riahi Kashani N, Nikzad H, et al. The novel coronavirus disease-2019 (COVID-19): mechanism of action, detection and recent therapeutic strategies. Virology 2020; 551: 1–9.
Crossref
PubMed
Google Scholar
2. Polack FP, Thomas SJ, Kitchin N, et al.; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383: 2603–2615.
Crossref
PubMed
Google Scholar
3. Achiron A, Dolev M, Menascu S, et al. COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021. MSJ 2021.https://doi.org/10.1177/13524585211003476.
Google Scholar
4. Longbrake EE, Cross AH. Effect of multiple sclerosis disease-modifying therapies on B cells and humoral immunity. JAMA Neurol 2016; 73: 219–225.
Crossref
PubMed
Web of Science
Google Scholar
5. Schweitzer F, Laurent S, Fink GR, et al. Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis. J Neurol. Epub ahead of print 8 February 2020.
Crossref
Google Scholar
6. Frampton JE. Ocrelizumab: first global approval. Drugs 2017; 77: 1035–1041.
Crossref
PubMed
Google Scholar
7. Miyazaki Y, Niino M, Fukazawa T, et al. Suppressed pro-inflammatory properties of circulating B cells in patients with multiple sclerosis treated with fingolimod, based on altered proportions of B-cell subpopulations. Clin Immunol 2014; 151: 127–135.
Crossref
PubMed
Web of Science
Google Scholar
8. Ceronie B, Jacobs BM, Baker D, et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol 2018; 265: 1199–1209.
Crossref
PubMed
Web of Science
Google Scholar
9. Jacobs BM, Ammoscato F, Giovannoni G, et al. Cladribine: mechanisms and mysteries in multiple sclerosis. J Neurol Neurosurg Psychiatry 2018; 89: 1266–1271.
Crossref
PubMed
Web of Science
Google Scholar
10. EUROIMMUN. Anti-SARS-CoV-2 ELISA IgG, [Package Insert]. Moutain Lakes, NJ: EUROIMMUN US, 2020.
Google Scholar
11. Zheng C, Kar I, Chen CK, et al. Multiple sclerosis disease-modifying therapy and the COVID-19 pandemic: implications on the risk of infection and future vaccination. CNS Drugs 2020; 34: 879–896.
Crossref
PubMed
Google Scholar
12. Arkhipova-Jenkins I, Helfand M, Armstrong C, et al. Antibody response after SARS-CoV-2 infection and implications for immunity: a rapid living review. Ann Intern Med. Epub ahead of print 16 March 2021.
Crossref
PubMed
Google Scholar
13. Nayak K, Gottimukkala K, Kumar S, et al. Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India. Virology 2021; 558: 13–21.
Crossref
PubMed
Google Scholar
14. Mendrone-Junior A, Dinardo CL, Ferreira SC, et al. Correlation between SARS-COV-2 antibody screening by immunoassay and neutralizing antibody testing. Transfusion 2021; 61: 1181–1190.
Crossref
PubMed
Google Scholar
15. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 2020; 586: 594–599.
Crossref
PubMed
Google Scholar
16. Roy S, Boschert U. Analysis of influenza and varicella zoster virus vaccine antibody titers in patients with relapsing multiple sclerosis treated with cladribine tablets. Poster presented at ACTRIMS, 25–27 February 2021, Virtual Congress.
Google Scholar
17. Wu GF, Boschert U, Hayward B, et al. Evaluating the impact of Cladribine tablets on the development of antibody titers: interim results from the CLOCK-MS influenza vaccine sub-study. Poster presented at ACTRIMS Forum, 25–27 February 2021, Virtual.
Google Scholar
18. Kaufmann M, Haase R, Proschmann U, et al. Real world lab data: patterns of lymphocyte counts in fingolimod treated patients. Front Immunol 2018; 9: 2669.
Crossref
Google Scholar
19. Luna G, Alping P, Burman J, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol 2020; 77: 184–191.
Crossref
PubMed
Web of Science
Google Scholar
20. Bar-Or A, Calkwood JC, Chognot C, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: the VELOCE study. Neurology 2020; 95: e1999–e2008.
Crossref
PubMed
Google Scholar
21. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology 2015; 84: 872–879.
Crossref
PubMed
Web of Science
Google Scholar
22. Fernández-Velasco JI, Kuhle J, Monreal E, et al. Effect of ocrelizumab in blood leukocytes of patients with primary progressive MS. Neurol Neuroimmunol Neuroinflamm 2021; 8: e940.
Crossref
PubMed
Google Scholar
23. Loarce-Martos J, García-Fernández A, López-Gutiérrez F, et al. High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study. Rheumatol Int 2020; 40: 2015–2021.
Crossref
PubMed
Google Scholar

Cite article

Cite article

Cite article

OR

Download to reference manager

If you have citation software installed, you can download article citation data to the citation manager of your choice

Share options

Share

Share this article

Share with email
Email Article Link
Share on social media

Share access to this article

Sharing links are not relevant where the article is open access and not available if you do not have a subscription.

For more information view the Sage Journals article sharing page.

Information, rights and permissions

Information

Published In

Volume 14
Article first published online: April 22, 2021
Issue published: January-December 2021

Keywords

  1. COVID-19
  2. humoral immune response
  3. mRNA vaccine
  4. multiple sclerosis
  5. SARS-COV-2 IgG

Rights and permissions

© The Author(s), 2021.
Creative Commons License (CC BY-NC 4.0)
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Request permissions for this article.
PubMed: 34035836

Authors

Affiliations

Anat Achiron
Multiple Sclerosis Center, Sheba Medical Center and The Laura Schwarz-Kipp Research of Autoimmune Diseases, Sackler School of Medicine, Tel-Aviv University, Israel, 2 Derech Sheba, Ramat-Gann, 52621, Israel
https://orcid.org/0000-0002-2020-3126
[email protected]
View all articles by this author
Mathilda Mandel
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Sapir Dreyer-Alster
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Gil Harari
School of Public Health, University of Haifa, Israel
View all articles by this author
David Magalashvili
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Polina Sonis
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Mark Dolev
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Shay Menascu
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, and Sackler School of Medicine, Tel-Aviv University, Israel
View all articles by this author
Shlomo Flechter
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Rina Falb
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel
View all articles by this author
Michael Gurevich
Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, and Sackler School of Medicine, Tel-Aviv University, Israel
View all articles by this author

Notes

Metrics and citations

Metrics

Journals metrics

This article was published in Therapeutic Advances in Neurological Disorders.

View All Journal Metrics

Article usage*

Total views and downloads: 39540

*Article usage tracking started in December 2016

Altmetric

See the impact this article is making through the number of times it’s been read, and the Altmetric Score.
Learn more about the Altmetric Scores


Articles citing this one

Receive email alerts when this article is cited

Web of Science: 281 view articles Opens in new tab

Crossref: 193

  1. Extensive T-Cell Profiling Following SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs
    Go to citationCrossrefGoogle Scholar
  2. Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study
    Go to citationCrossrefGoogle Scholar
  3. Induction of Antigen-Specific Tolerance in a Multiple Sclerosis Model without Broad Immunosuppression
    Go to citationCrossrefGoogle Scholar
  4. Safety of COVID-19 Vaccines in Patients With Multiple Sclerosis: A Cross-Sectional Study From a Tertiary Rehabilitation Center in Saudi Arabia
    Go to citationCrossrefGoogle Scholar
  5. The Impact of Disease-Modifying Therapies of Multiple Sclerosis on the Effectiveness of the BBIBP-CorV COVID-19 Vaccine
    Go to citationCrossrefGoogle Scholar
  6. COVID-19 Vaccination Response in Patients with Multiple Sclerosis Treated with Ofatumumab in the United States: A Medical Record Review
    Go to citationCrossrefGoogle Scholar
  7. Pharmacoproteomics
    Go to citationCrossrefGoogle Scholar
  8. Anti-RBD Antibody Levels and IFN-γ-Specific T Cell Response Are Associated with a More Rapid Swab Reversion in Patients with Multiple Sclerosis after the Booster Dose of COVID-19 Vaccination
    Go to citationCrossrefGoogle Scholar
  9. Do immunosuppressive treatments influence immune responses against adenovirus-based COVID-19 vaccines in patients with multiple sclerosis? An Argentine multicenter study
    Go to citationCrossrefGoogle Scholar
  10. The effect of COVID‐19 vaccination on multiple sclerosis activity as reflected by MRI
    Go to citationCrossrefGoogle Scholar
  11. View More

Figures and tables

Figures & Media

Tables

View Options

View options

PDF/EPUB

View PDF/EPUB

Access options

If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:

Alternatively, view purchase options below:

Purchase 24 hour online access to view and download content.

Subscribe to this journal

Access journal content via a DeepDyve subscription or find out more about this option.

Start 2 week free trial
Need help?

Also from Sage