Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19

Aggarwal, A.; Singh, T. K.; Pham, M.; Godwin, M.; Chen, R.; McIntyre, T. M.; Chung, M. K.; Jennings, C.; Ali, M.; Park, H.; Englund, K.; Khorana, A. A.; Svensson, L.; Kapadia, S. R.; McCrae, K. R.; Cameron, S. J.

doi:10.1101/2023.06.18.545507

bioRxiv · 10.1101/2023.06.18.545507

Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19

Aggarwal, A.·Singh, T. K.·Pham, M.·Godwin, M.·Chen, R.·McIntyre, T. M.·Chung, M. K.·Jennings, C.·Ali, M.·Park, H.·Englund, K.·Khorana, A. A.·Svensson, L.·Kapadia, S. R.·McCrae, K. R.·Cameron, S. J.

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Abstract

BackgroundPost-acute sequelae of COVID-19 (PASC), also referred as Long-COVID, sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. AimOur objective was to evaluate the platelet function and thrombotic potential in patients following recovery from SARS-CoV-2 with clear symptoms of PASC. MethodsPASC patients and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions. ResultsA mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals. ConclusionsPASC patients show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

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Aggarwal, A., Singh, T. K., Pham, M., Godwin, M., Chen, R., McIntyre, T. M., Chung, M. K., Jennings, C., Ali, M., Park, H., Englund, K., Khorana, A. A., Svensson, L., Kapadia, S. R., McCrae, K. R., Cameron, S. J.. 2023-06-19. Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19. https://doi.org/10.1101/2023.06.18.545507

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