Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a prothrombotic stimulus for platelets.
Blood
; 138(16): 1481-1489, 2021 10 21.
Article
in English
| MEDLINE | ID: covidwho-1484294
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Thrombosis
/
Blood Platelets
/
Immunoglobulin G
/
Von Willebrand Factor
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Topics:
Long Covid
Limits:
Humans
Language:
English
Journal:
Blood
Year:
2021
Document Type:
Article
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