Abstract
BackgroundThrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID-19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality. Platelets are essential cells that regulate hemostasis, thrombus formation and inflammation; however, the mechanism underlying the interaction between platelets and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear.ResultsThe present study performed RNA sequencing on the RNA isolated from platelets obtained from 10 COVID-19 patients and eight healthy donors, and discovered that SARS-CoV-2 not only significantly altered the coding and non-coding transcriptional landscape, but also altered the function of the platelets, promoted thrombus formation and affected energy metabolism of platelets. Integrative network biology analysis identified four key subnetworks and 16 risk regulators underlying SARS-CoV-2 infection, involved in coronavirus disease-COVID-19, platelet activation and immune response pathways. Furthermore, four risk genes (upstream binding transcription factor, RNA polymerase II, I and III subunit L, Y-box binding protein 1 and yippee like 2) were found to be associated with COVID-19 severity. Finally, a significant alteration in the von Willebrand factor/glycoprotein Ib-IX-V axis was revealed to be strongly associated with platelet aggregation and immunothrombosis.ConclusionsThe transcriptional landscape and the identification of critical subnetworks and risk genes of platelets provided novel insights into the molecular mechanisms of immunothrombosis in COVID-19 progression, which may pave the way for the development of novel therapeutic strategies for preventing COVID-19-associated thrombosis and improving the clinical outcome of COVID-19 patients.
Highlights
Thrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality
The C reactive protein (CRP) levels were significantly increased in the COVID-19 patient group, whereas the lymphocyte count was notably decreased, which is consistent with previous reports that found that elevated CRP levels and lymphopenia were the main laboratory characteristics of COVID-19 patients [36,37,38,39]
Since the outbreak of COVID-19, an increasing number of studies have reported the hyperactivity of activated platelets in COVID-19 patients [26, 42, 43], and their role in immunothrombosis induced by SARS-CoV-2 [20, 44]
Summary
Thrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality. Accumulating evidence has suggested that thrombosis and coagulopathy are pervasive pathological features of COVID-19 [10, 11]. Compared with other respiratory infectious diseases, COVID-19 shows a higher cumulative incidence of thrombotic complications [12,13,14], especially in COVID-19 patients admitted to intensive care units (ICUs) [15, 16]. The thrombotic complications of COVID-19 patients are associated with multiple organ failure and increased mortality [19, 20]
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