Abstract
A subset of patients with coronavirus disease 2019 (COVID-19) become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill patients with COVID-19 are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesized that platelets might be susceptible to activation by anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies and might contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike immunoglobulin G enhanced platelet-mediated thrombosis on von Willebrand factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on FcγRIIA, and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by the therapeutic small molecules R406 (fostamatinib) and ibrutinib, which inhibit tyrosine kinases Syk and Btk, respectively, or by the P2Y12 antagonist cangrelor.
【초록키워드】 COVID-19, coronavirus disease, platelet activation, coronavirus, thrombosis, adaptive, severe COVID-19, Immunity, glycosylation, antibody, in vitro, anti-SARS-CoV-2, immune complex, Critically ill, Immunoglobulin, SARS-CoV-2 spike protein, therapeutic, Patient, von Willebrand factor, Platelet, small molecule, Critical, Anti-spike, Evidence, tyrosine, acute respiratory syndrome, Activation, domain, pathogenic, excessive immune response, kinase, susceptible, inhibit, contribute, dependent on, cause, subset, P2Y12, respiratory problem, severely ill patient, the timing, with COVID-19, 【제목키워드】 glycosylation, anti-SARS-CoV-2, Platelet, spike IgG, prothrombotic,