Fingolimod impairs inactivated vaccine (CoronaVac)-induced antibody response to SARS-CoV-2 spike protein in persons with multiple sclerosis

Türkoğlu, Recai; Baliç, Nesrin; Kızılay, Tuğçe; Erol, Ruziye; Akbayır, Ece; Yılmaz, Vuslat; Tüzün, Erdem

doi:10.1016/j.msard.2022.103524

Cited by 8 publications

(8 citation statements)

References 7 publications

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“… 23 Therefore, although accumulating evidence and our results confirmed that S1PRM therapy blunted responses to SARS-CoV-2 vaccination, the impact of this treatment on COVID-19 outcomes in pwMS remains to be elucidated. Moreover, several studies identified a negative correlation between humoral response after COVID-19 vaccination and treatment duration of S1PRMs, 46 , 47 which deserves further verification.…”

Section: Discussionmentioning

confidence: 84%

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

Wang

Shen

et al. 2022

eBioMedicine

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Section: Discussionmentioning

confidence: 84%

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

Wang

Shen

et al. 2022

eBioMedicine

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“…High-certainty evidence confirms significantly lower odds of post-vaccination seroconversion in pwMS on S1PRM compared with UX people (OR [95%CI]: 0.04 [0.03, 0.06], P<0.00001) (Supplementary Figure 5). All included studies 16,17,19-22,25-31 found significantly lower concentrations of antibodies following vaccination in these pwMS compared to UX people. Studies with heterogenous effect measures (moderate-certainty evidence) indicate that with the current vaccination strategy, pwMS on S1PRM are 25 times (95%CI: 16.66, 33.33) less likely to show anti-S1, and 8.33 times (95%CI: 3.70, 20) less likely to show anti-S seroconversion following COVID-19 vaccination (Chi 2 =7.24, P<0.01).…”

Section: Resultsmentioning

confidence: 93%

“…All included studies 16,17,[19][20][21][22][25][26][27][28][29][30][31] , headto-head mRNA-AV 29 and mRNA-inactivated 22 immunogenicity comparisons in S1PRM-treated pwMS have suggested the opposite. Hence, the need for more replication of inactivated/mRNA/AV comparisons is clearly sensed for pwMS on S1PRM.…”

Section: Sphingosine-1-phosphate Receptor Modulators (S1prm)mentioning

confidence: 99%

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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Importance: An evidence-based appraisal of the COVID-19 vaccination policies among people with multiple sclerosis (pwMS) with respect to disease-modifying therapies (DMT) is important for our understandings and their further management. Objective: To synthesize the available evidence concerning the effect of DMTs on COVID-19 vaccination immunogenicity and effectiveness. Data Sources: We searched MEDLINE, Scopus, Web of Science, MedRxiv, and Google Scholar from January 2021 until January 2022. Study Selection: The exclusion criteria included: not a primary investigation; retracted/withdrawn; no eligible participants - people with no history/evidence of previous COVID-19 and corticosteroid administration within two months of vaccination; no eligible exposures - all nine DMT classes; and no eligible comparators - DMT-unexposed at the time of vaccination. Data Extraction and Synthesis: Entries were assessed independently by two reviewers for eligibility and quality. Dichotomized data was extracted by two reviewers in accordance with Cochrane guidelines, and were pooled using either Peto fixed-effects or Inverse-variance random-effects methods. Main Outcomes and Measures: Main outcomes were i) B-cell response, measured by seroconversion odds ratio (OR); ii) T-cell response, measured by interferon-gamma release response OR, and CD4+/CD8+ activation-induced marker+ OR. Further outcomes including immunity waning speed and breakthrough COVID-19 incidence/severity were synthesized narratively. Results: Data from 28 studies (5,025 pwMS and 1,635 healthy participants) after COVID-19 vaccination suggests mildly-lower B-cell responses in teriflunomide- and alemtuzumab-treated, extensively-lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM)- and anti-CD20 (aCD20)-treated, and lower T-cell responses in interferon-, S1PRM-, alemtuzumab- and cladribine-treated pwMS. Every ten-week increase in aCD20-to-vaccine period is associated with a 1.94-time (95%CI: 1.57, 2.41, P<0.00001) increase in odds of seroconversion. B-cell-depleting therapies seem to accelerate post-vaccination humoral waning, and booster immunogenicity is predictable with the same factors affecting the priming vaccination. Furthermore, comparatively-increased breakthrough COVID-19 incidence and severity is being observed only among S1PRM- and anti-CD20-treated pwMS - i.e., among the pwMS with extensively-blunted B-cell response, despite adequate T-cell responses in the aCD20-treated. To date, pwMS on only-T-cell-blunting DMTs have not shown increased susceptibility to breakthrough COVID-19. Conclusion and Relevance: The implemented vaccination strategy to date has been effective for pwMS on all DMTs other than S1PRM and aCD20. As B-cell immunity seems to be a more important predictor of vaccine effectiveness than T-cell immunity, optimization of humoral immunogenicity and ensuring its durability among pwMS on DMTs are the necessities of an effective COVID-19 vaccination policy.

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“…S1PRM extensively decrease the odds of post-vaccine seroconversion (OR (95% CI): 0.04 (0.03 to 0.06), p<0.00001) (online supplemental figure 5), according to evidence with high certainty. In all of the included studies,10 11 13–16 19–25 the S1PRM-treated pwMS had significantly lower concentrations of post-vaccine antibodies when compared with UX people; the effect measures were, however, heterogenous. Therefore, evidence indicates with moderate certainty that pwMS on S1PRM are 25 times (95% CI: 16.66 to 33.33) less likely to show anti-S1, and 8.33 times (95% CI: 3.70 to 20) less likely to show anti-S seroconversion following COVID-19 vaccination (χ 2 =7.24, p<0.01).…”

Section: Resultsmentioning

confidence: 97%

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

Etemadifar

Nouri

Pitzalis

et al. 2022

J Neurol Neurosurg Psychiatry

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Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines’ immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS—although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters’ immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20—unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.

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Fingolimod impairs inactivated vaccine (CoronaVac)-induced antibody response to SARS-CoV-2 spike protein in persons with multiple sclerosis

Cited by 8 publications

References 7 publications

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

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

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

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