Abstract
Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platelet activation during SARS-CoV-2 infection. During COVID-19, a lower plasmatic L-arginine level was observed compared to healthy donors, which correlated with MDSC frequency. Additionally, activated GPIIb/IIIa complex (PAC-1) expression was higher on platelets from severe COVID-19 patients compared to healthy controls and inversely correlated with L-arginine plasmatic concentration. Notably, MDSC were able to induce PAC-1 expression in vitro by reducing L-arginine concentration, indicating a direct role of PMN-MDSC in platelet activation. Accordingly, we found a positive correlation between ex vivo platelet PAC-1 expression and PMN-MDSC frequency. Overall, our data demonstrate the involvement of PMN-MDSC in triggering platelet activation during COVID-19, highlighting a novel role of MDSC in driving COVID-19 pathogenesis.
Highlights
Our results showed a novel role of PMN-myeloid-derived suppressor cells (MDSC) from COVID-19 patients, being able to increase platelet activation by reducing L-arginine concentration, contributing to the platelet hyperactivity observed in severe COVID-19
Plasmatic L-Arginine in COVID-19 Patients was Correlated to PMN-MDSC Frequency
We evaluated the plasmatic concentration of L-arginine in patients with moderate
Summary
Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platelet activation during SARS-CoV-2 infection. COVID-19 patients compared to healthy controls and inversely correlated with L-arginine plasmatic concentration. MDSC were able to induce PAC-1 expression in vitro by reducing L-arginine concentration, indicating a direct role of PMN-MDSC in platelet activation. We found a positive correlation between ex vivo platelet PAC-1 expression and PMN-MDSC frequency. In severe COVID-19, coagulation abnormalities appear, inducing a hypercoagulable state and an increased rate of thrombotic and thromboembolic events [2]. The expression of SARS-CoV-2 receptor (angiotensin converting enzyme 2, ACE-2) on platelet membranes suggests a possible direct role of SARS-CoV-2 in platelet activation [4]
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