The following is a summary of the “Impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination,” published in the January 2023 issue of Multiple Sclerosis and Related Disorders by Baker, et al.

Modulating the sphingosine-1 phosphate receptor (S1PR) reduces S1PR1-mediated lymphocyte migration, stops lesion formation, and benefits active multiple sclerosis (MS). The pharmacokinetics, metabolic profiles, and S1PR receptor affinities of these S1PR modulatory medications will likely affect MS-management. They also generate immune responses to SARS-CoV-2 vaccines and have shown beneficial in combating COVID-19. To evaluate the impact of current sphingosine-one-phosphate modulators used in treating multiple sclerosis of the biology and new facts that may underlie immunity to the SARS-CoV-2 virus following natural infection and vaccination. Infection, vaccine response, S1PR distribution, and functional activity data were all culled from published regulatory and scholarly sources.

Fingolimod treatment is the primary focus of most available data on COVID-19. This suggests that sustained regulation of S1PR1, S1PR3, S1PR4, and S1PR5 is not linked to a poorer prognosis after SARS-CoV-2 infection. People taking siponimod, ozanimod, and ponesimod appear to exhibit stronger vaccine responses, which may be related particularly to a limited impact on S1PR4 activity, in contrast to those taking fingolimod, which is associated with blunted seroconversion and reduced peripheral T-cell vaccine responses. Although it has been hypothesized that S1PR3, in addition to acts by S1PR1 and S1PR2, regulates B cell function, this may be a species-specific impact in rats that has not yet been confirmed in humans, as demonstrated with bradycardia concerns. 

Actions on B- and T-cell subsets, germinal center activity, and innate-immune biology have all been linked to attenuated antibody responses. Newer generations of S1PR modulators may boost the rate of vaccine-induced seroconversion and improve the risk-benefit balance, even though S1P1R-related functions appear crucial to MS control and the production of a fully functioning vaccination response. Although fingolimod is a valuable tool in managing MS, recently approved S1PR modulators may have advantageous biology in terms of pharmacokinetics, metabolism, and more-restricted targeting, making it simpler to generate infection-control and effective anti-viral responses against SARS-COV-2 and other pathogens. There should be more research done.

Source: sciencedirect.com/science/article/pii/S2211034822009294