Atrioventricular block after fingolimod resumption: a consequence of sphingosine-1-phosphate axis alteration due to COVID-19?

Abstract

During the COVID-19 pandemic, concerns raised regarding the use of immunosuppressants in multiple sclerosis, even if current data do not support an increased risk of infection. Although fingolimod can be temporarily suspended during COVID-19, the benefit-risk balance of suspension can be challenging. Till now, no adverse events have been described after the resumption of fingolimod, following a previous discontinuation. We report the occurrence of atrioventricular block following fingolimod restart. Fingolimod acts on sphingosine-1-phosphate-axis, a pathway that is altered with COVID-19 and hypoxic conditions. Herein we discuss how these metabolic changes may have influenced fingolimod pharmacology leading to a cardiac event.

Keywords: Atrioventricular block; COVID-19; Fingolimod; Sphingosine 1-phosphate.

Fig. 1

Fingolimod metabolism. Three critical points potentially altered in the reported case. Abbreviation: SphK (sphingosine kinase)

Fig. 2

Possible mechanisms determining the occurrence of atrioventricular block in the reported case. Increase in fingolimod-phosphate (bioactive form) and in S1PR expression during COVID-19 compared to the homeostatic condition. This condition could lead to greater activation of GIRK channels causing cardiac event. Abbreviation: FTY (green balls), fingolimod; FTY-P (yellow balls), fingolimod-phosphate; S1PR (blue receptors), sphingosine 1-phosphate receptor; GIRK (red channels), G-protein–coupled inwardly rectifying potassium; K⁺, potassium. Created with BioRender.com