Dataset Information

Response of COVID-19 vaccination in multiple sclerosis patients following disease-modifying therapies: A meta-analysis.

ABSTRACT:

Background

COVID-19 vaccination is recommended for patients with multiple sclerosis (pwMS), while disease-modifying therapies (DMTs) may influence the efficacy of SARS-CoV-2 vaccines in this population. Thus, we conducted a meta-analysis to evaluate the impact of DMTs on immune response to COVID-19 vaccines in pwMS.

Methods

Literature search from December 1, 2019 to March 31, 2022 was performed in PubMed, MedRxiv, Embase and Cochrane Library. The risk of impaired response to vaccination in pwMS receiving DMTs was estimated in odds ratios (ORs) using random-effects method.

Findings

A total of 48 studies comprising 6860 pwMS were included. Overall, pwMS with anti-CD20 (OR=0.02, 95% CI: 0.01-0.03) and sphingosine-1-phosphate receptor modulator (S1PRM) (OR=0.03, 95% CI: 0.01-0.06) treatments had attenuated serologic response after full vaccination compared with those without DMTs. Additionally, pwMS vaccinated within six months since last anti-CD20 therapy were at significantly higher risk of blunted response compared with those receiving anti-CD20 therapy more than six months prior to vaccination (P = 0.001). We found no significant associations between other treatments (including IFN-β, GA, DMF, TERI, NTZ, CLAD, and ALE) and humoral response to SARS-CoV-2 vaccines in pwMS. As for T-cell response, no significant difference was found between pwMS on anti-CD20 and those without DMTs after vaccination, while S1PRM was marginally associated with impaired cellular response (P = 0.03).

Interpretation

Our findings suggested that routine serological monitoring may be required for pwMS on anti-CD20 and S1PRMs after SARS-CoV-2 vaccination and highlighted the benefits of a booster dose. The effect of cellular response and optimal interval from last anti-CD20 treatment to vaccination should be further addressed.

Funding

This study was supported by Natural Science Foundation of Shanghai (21ZR1433000).

SUBMITTER: Wu X

PROVIDER: S-EPMC9230320 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.MethodsThe aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled "responding T-cells", those cells that produced at least one of the three cytokines of interest, and "triple positive T-cells", those cells that produced simultaneously all the three cytokines.ResultsThe cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).ConclusionIn pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

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