SARS-CoV-2 Spike Protein and Neutralizing Anti-Spike Protein Antibodies Modulate Blood Platelet Function

Abstract

Several studies report elevated blood platelet activation and altered platelet count in COVID-19 patients, but the role of the SARS-CoV-2 spike protein in this process remains intriguing. Additionally, there is no data that anti-SARS-CoV-2 neutralizing antibodies (nAb) may attenuate spike protein activity toward blood platelets. Our results indicate that under in vitro conditions, the spike protein increased the collagen-stimulated aggregation of isolated platelets and induced the binding of vWF to platelets in ristocetin-treated blood. The spike protein also significantly reduced collagen- or ADP-induced aggregation or decreased GPIIbIIIa (fibrinogen receptor) activation in whole blood, depending on the presence of the anti-spike protein nAb. Our findings suggest that studies on platelet activation/reactivity in COVID-19 patients or in donors vaccinated with anti-SARS-CoV-2 and/or previously-infected COVID-19 should be supported by measurements of spike protein and IgG anti-spike protein antibody concentrations in blood.

Digital holo-tomographic 3D maps of COVID-19 microclots in blood to assess disease severity

“…Additionally, the dysregulated immune response triggered by the viral infection can lead to excessive inflammation and cytokine release, further promoting a pro-thrombotic state ( 21 ). More specifically, COVID-19-related coagulopathy was associated with elevated levels of von Willebrand Factor (VWF), D-dimer, fibrinogen, and markers of platelet activation, as well as damaged red blood cells (RBCs) and reduced fibrinolysis, reflecting ongoing coagulation activation ( 3, 22, 23 ). In long COVID, persistent coagulation abnormalities may contribute to the chronic and debilitating symptoms experienced by affected individuals ( 1, 8, 24 ).…”

3D Holo-tomographic Mapping of COVID-19 Microclots in Blood to Assess Disease Severity

“…21 More specifically, COVID-19-related coagulopathy was associated with elevated levels of von Willebrand Factor (VWF), D-dimer, fibrinogen, and markers of platelet activation, as well as damaged red blood cells (RBCs) and reduced fibrinolysis, reflecting ongoing coagulation activa- tion. 3,22,23 In long COVID, persistent coagulation abnormalities may contribute to the chronic and debilitating symptoms experienced by affected individuals. 1,8,24 The formation of microclots, or microthrombi, within the pulmonary vasculature has been observed, contributing to respiratory compromise.…”

“…The pathogenic mechanisms underlying coagulopathy in COVID-19 and long COVID are complex and multifactorial, including a patient’s pre-existing conditions. , The presence of SARS-CoV-2 has been detected within endothelial cells, suggesting a direct viral effect on the vascular system. , Additionally, the dysregulated immune response triggered by the viral infection can lead to excessive inflammation and cytokine release, further promoting a pro-thrombotic state . More specifically, COVID-19-related coagulopathy was associated with elevated levels of von Willebrand Factor (VWF), D-dimer, fibrinogen, and markers of platelet activation, as well as damaged red blood cells (RBCs) and reduced fibrinolysis, reflecting ongoing coagulation activation. ,, In long COVID, persistent coagulation abnormalities may contribute to the chronic and debilitating symptoms experienced by affected individuals. ,, The formation of microclots, or microthrombi, within the pulmonary vasculature has been observed, contributing to respiratory compromise. ,, The mechanisms underlying these persistent coagulation disturbances are not yet fully understood, but they may involve a combination of residual inflammation, immune dysregulation, and vascular damage. ,, …”