Enhanced platelet sensitization is accompanied by increased expression of the transporter MRP4 and elevated plasma S1P levels in mild COVID-19 convalescents
Creators: name: Tolksdorf, Céline
name: Seidel, Andrea
name: Baume, Christian
name: Moritz, Eileen
name: Saljé, Karen
name: Lehmann, Kathrin
name: Becker, Karsten
name: Garscha, Ulrike
name: Thiele, Thomas
name: Schwedhelm, Edzard
name: von Lucadou, Mirjam
name: Tzvetkov, Mladen V.
name: Engeli, Stefan
name: Jedlitschky, Gabriele
name: Rauch, Bernhard H.
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Medicine
subject: Physiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Mental Health
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: Viral infections can lead to platelet activation and hemostatic complications. However, the extent to which platelet reactivity remains altered after convalescence, contributing to long-term health impairments as observed after COVID-19 is not yet fully understood. Therefore, we conducted a cohort study (DRKS00025217) to determine platelet function in individuals convalesced from mild COVID-19. Assays were performed <i>ex vivo</i> with blood from convalescents at 2–15 weeks and 6–10 months after convalescence, focusing on platelet aggregation, activation markers, and thrombin formation. In addition, two other potentially relevant factors for platelet function were examined: the immunomodulatory mediator sphingosine-1-phosphate (S1P) and the platelet expression of the transporter MRP4 (ABCC4). Our findings indicate that robust platelet functions, including platelet aggregation determined by light transmission aggregometry, and thrombin formation, were not altered in convalescents compared to matched control individuals. However, an elevation in subtle platelet activation markers, such as P-selectin surface expression and activation of glycoprotein IIb/IIIa, was observed 2–15 weeks after convalescence. This was accompanied by an increased expression of MRP4 in platelets and significantly elevated levels of S1P in platelet-poor plasma. Our findings suggest increased platelet sensitization and a pro-inflammatory state even after convalescence from mild COVID-19, pointing toward MRP4 and S1P as associated factors. <b>What is the context?</b>Viral infectious diseases can cause thrombotic events due to inflammation and hypercoagulability as seen in COVID-19.Due to the lack of data on how platelet function is affected after a viral infection, possible underlying mechanisms that can be attributed to platelet sensitization have not yet been sufficiently investigated. Viral infectious diseases can cause thrombotic events due to inflammation and hypercoagulability as seen in COVID-19. Due to the lack of data on how platelet function is affected after a viral infection, possible underlying mechanisms that can be attributed to platelet sensitization have not yet been sufficiently investigated. <b>What is the aim of the study?</b>The aim of our longitudinal cohort study was to determine whether platelet function is altered after a systemic infection by using the example of a mild course of coronavirus disease 2019 (COVID–19). The aim of our longitudinal cohort study was to determine whether platelet function is altered after a systemic infection by using the example of a mild course of coronavirus disease 2019 (COVID–19). <b>What are the results of our study?</b>Elevated markers of platelet reactivity such as P-selectin surface expression and activated GPIIb/IIIa indicate an increased platelet sensitization in convalescents within 2–15 weeks after convalescence from mild COVID–19.In addition, our study shows for the first time an increased platelet expression of MRP4, a transporter whose activity critically influences platelet function and elevated plasma levels of the immunomodulatory mediator S1P. Both factors may be related to the enhanced platelet reactivity and inflammatory responses post infection. Elevated markers of platelet reactivity such as P-selectin surface expression and activated GPIIb/IIIa indicate an increased platelet sensitization in convalescents within 2–15 weeks after convalescence from mild COVID–19. In addition, our study shows for the first time an increased platelet expression of MRP4, a transporter whose activity critically influences platelet function and elevated plasma levels of the immunomodulatory mediator S1P. Both factors may be related to the enhanced platelet reactivity and inflammatory responses post infection. <b>What is the impact?</b>Our findings add new details to a better understanding of the role of platelets in viral infections, specifically in the less well-understood prolonged effects in milder COVID–19 cases. This could provide new approaches for combating complications during and after viral diseases. Our findings add new details to a better understanding of the role of platelets in viral infections, specifically in the less well-understood prolonged effects in milder COVID–19 cases. This could provide new approaches for combating complications during and after viral diseases.