ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) has been recognized as a disease with a broad spectrum of clinical manifestations. In this report, we illustrate an extraordinary case of severe cardioinhibitory reflex syncope with prolonged asystole associated with COVID-19. CASE SUMMARY: A 35-year-old male patient presented to the emergency department with a 10-day history of postural syncope and fever. Electrocardiogram monitoring during positional change revealed reflex syncope with cardioinhibitory response, exhibiting sinus bradycardia, subsequent asystole, and syncope. The patient tested positive for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and was admitted to the intensive care unit where temporary transvenous pacing was necessary because of prolonged episodes of asystole. Work-up included extensive cardiac and neurological diagnostic testing, but did not yield any structural abnormalities. Although temporary pacing was able to abort syncope, a decision was made to hold off on permanent pacing as the most likely aetiology was felt to be temporary cardioinhibitory reflex syncope associated with COVID-19. The patient was discharged with mild symptoms of orthostatic intolerance and responded well to education and lifestyle modification. Outpatient follow-up with repeat tilt testing after 3 and 6 months initially showed residual inducible syncope but was eventually normal and the patient remained asymptomatic. DISCUSSION: We believe that autonomic imbalance with a strong vagal activation due to acute SARS-CoV-2 infection played a pivotal role in the occurrence of transient syncope in this patient's condition. Although pacemaker implantation would have been a reasonable alternative, a watch-and-wait approach should be considered in similar instances.
ABSTRACT
RATIONALE: Platelets are known to play a crucial role in hemostasis. Sphingosine kinases (Sphk) 1 and 2 catalyze the conversion of sphingosine to the bioactive metabolite sphingosine 1-phosphate (S1P). Although platelets are able to secrete S1P on activation, little is known about a potential intrinsic effect of S1P on platelet function. OBJECTIVE: To investigate the role of Sphk1- and Sphk2-derived S1P in the regulation of platelet function. METHODS AND RESULTS: We found a 100-fold reduction in intracellular S1P levels in platelets derived from Sphk2(-/-) mutants compared with Sphk1(-/-) or wild-type mice, as analyzed by mass spectrometry. Sphk2(-/-) platelets also failed to secrete S1P on stimulation. Blood from Sphk2-deficient mice showed decreased aggregation after protease-activated receptor 4-peptide and adenosine diphosphate stimulation in vitro, as assessed by whole blood impedance aggregometry. We revealed that S1P controls platelet aggregation via the sphingosine 1-phosphate receptor 1 through modulation of protease-activated receptor 4-peptide and adenosine diphosphate-induced platelet activation. Finally, we show by intravital microscopy that defective platelet aggregation in Sphk2-deficient mice translates into reduced arterial thrombus stability in vivo. CONCLUSIONS: We demonstrate that Sphk2 is the major Sphk isoform responsible for the generation of S1P in platelets and plays a pivotal intrinsic role in the control of platelet activation. Correspondingly, Sphk2-deficient mice are protected from arterial thrombosis after vascular injury, but have normal bleeding times. Targeting this pathway could therefore present a new therapeutic strategy to prevent thrombosis.
