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. 2024 Mar 12;12(3):296.
doi: 10.3390/vaccines12030296.

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis-A Real-World Scenario

Muriel Schraad  1 , Stefan Runkel  2 , Walter Hitzler  2 , Maria Protopapa  1 , Stefan Bittner  1 , Timo Uphaus  1 , Frauke Zipp  1
Affiliations

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis-A Real-World Scenario

Muriel Schraad et al. Vaccines (Basel). .

Abstract

Immunomodulatory and immunosuppressive therapy is needed in people with a chronic neuroinflammatory disease of the central nervous system such as multiple sclerosis (MS). Therefore, MS requires monitoring for and preventing against infectious diseases like SARS-CoV-2. Vaccination and anti-viral treatments are, in particular, recommended for elderly people and people at risk of a severe course of infection and of MS. Here, we asked whether repetitive infection or vaccination influenced responses upon receiving high efficacy treatments, namely sphingosine-1-phosphate receptor modulator (S1P) or anti-CD20 B cell antibody (anti-CD20) treatments. We performed a prospective real-world study of people with MS (pwMS) under S1P or anti-CD20 with repetitive exposure to the SARS-CoV-2 virus or vaccine. The measurement of anti-SARS-CoV-2 antibody titres was performed by two independent immunoassays after initial immunisation and after booster vaccination or infection. Other laboratory and clinical parameters were included in the analysis of influencing factors. As secondary outcomes, lymphocyte and immunoglobulin levels were observed longitudinally under intravenous and subcutaneous anti-CD20 treatment. In a long-term real-world cohort of 201 pwMS, we found that despite lymphopenia upon S1P drugs, the SARS-CoV-2 immunisation response increased both in selective and non-selective S1P (100% and 88% seroconversion, respectively), whereas those under anti-CD20 therapies merely exhibited a slight long-term increase in antibody titres (52% seroconversion). The latter was independent of immunoglobulin or total lymphocyte levels, which mostly remained stable. If the individual was immunised prior to therapy initiation, their levels of SARS-CoV-2 antibodies remained high under treatment. PwMS under non-selective S1P benefit from repetitive vaccination. The risk of an insufficient vaccination response mirrored by lower SARS-CoV-2 antibodies remains in pwMS receiving anti-CD20 treatment, even after repetitive exposure to the vaccine or virus. Due to the compromised vaccination response in CD20-depleting drugs, prompt antiviral treatment might be necessary.

Keywords: SARS-CoV-2; anti-CD20; booster vaccination; efficiency; multiple sclerosis; sphingosine-1-phopshate receptor modulator; vaccination.

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Conflict of interest statement

The authors declare no relevant conflicts of interest.

Figures

Figure 1
Figure 1
Schematic Overview. Study design with sample acquisition performed after initial immunisation and after booster vaccination or virus exposure. Within the timelines the proportion of seroconverted pwMS under sS1P (orange), nsS1P (green), and anti-CD20 (aCD20; lilac) are displayed. Anti-spike antibody levels (log10) under sS1P, nsS1P, and aCD20 after initial immunisation (blue) and after booster vaccination or infection (pink). Mean (dot) with standard deviation (bars). Lower limit of seroconversion (0.8 U/mL) displayed as its logarithm base (log10) through dotted line. Schematic display of modes of action of S1P and aCD20. S1P functionally antagonises S1P receptors and thus prevents egress of lymphocytes from lymph nodes. Anti-CD20 results in depletion of CD20-positive B cells. Reduced counts of lymphocytes and B cells in blood result in decreased autoinflammation in the central nervous system. Created with Biorender.
Figure 2
Figure 2
Difference in anti-spike SARS-CoV-2 vaccination titre between pwMS treated with ns-S1P and s-S1P decreases with repetitive vaccination. (A) Antibody levels (log10) after initial immunisation are significantly lower in pwMS under ns-S1P than under s-S1P. (B) With a booster vaccination or infection titre reaches similar levels between S1P subgroups. (C) With booster vaccination no significant influences on titre were determined in a multiple regression model. Regression coefficient B (dot) with 95% confidence interval (95%CI, whisker). (D) Booster increases proportion of high-responder and decreases proportion of non-responder in both ns-S1P and s-S1P treated without reaching significance (ns-S1P n = 17, s-S1P n = 13). (E) Antibody levels (log10) are similar between pwMS that were vaccinated (vax) under s-S1P (n = 20) and those that were vaccinated (vax) prior to (n = 7) treatment. ns = not significant, *** p < 0.001.
Figure 3
Figure 3
Booster response and longitudinal display of antibody levels prior and with anti- CD20 treatment. (A) Anti-spike SARS-CV-2 (log10) vaccination response under anti-CD20 (aCD20) after initial immunisation and after repetitive exposure to the virus (booster) shows a tendency to rise, without reaching significance. (B) With booster vaccination no significant influences on titre were determined in a multiple regression model. Regression coefficient B (dot) with 95% confidence interval (95%CI, whisker). (C) Distribution of titre divided into non-responder (<0.8 U/mL, blue), responder (0.8–5000 U/mL, pink), and high responder (>5000 U/mL, yellow) after initial immunisation and with booster. Responder increase with booster (Chi2 *** p < 0.001, n = 52). (D) Longitudinal comparison of seral titre levels (log10) acquired prior to and after initiation of therapy with ofatumumab (OFA, n = 17) or ocrelizumab (OCR, n = 6) in pwMS immunized prior to therapy initiation. ns = not significant, *** p < 0.001.
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