VACCINE-INDUCED IMMUNE THROMBOTIC THROMBOCYTOPENIA: A POSSIBLE PATHOGENETIC ROLE OF CHADOX1 NCOV- 19 VACCINE ENCODED SOLUBLE SARS-COV-2 SPIKE PROTEIN
European Stroke Journal
; 7(1 SUPPL):349, 2022.
Article
in English
| EMBASE | ID: covidwho-1928082
ABSTRACT
Background and aims:
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome of unclear aetiology occurring after vaccinations against COVID-19. The aim of this study was to investigate the DNA vaccine-encoded Sars-cov-2 soluble spike protein (SP) as a potential trigger of platelet activation in VITT.Methods:
We studied three VITT patients and seven healthy controls (HCs) within 3 weeks from the first dose of ChAdOx1 nCoV-19. Serum levels of SP, soluble angiotensin-converting enzyme 2 (sACE2), and platelet response to VITT serum stimulation were studied. A thrombus retrieved from middle cerebral artery during mechanical thrombectomy of one VITT patient, was analysed by immunohistochemistry for SP and ACE2. Neutrophil extracellular traps (NETs) markers and coagulation parameters were also measured.Results:
We detected SP and sACE2 in all VITT patients, and in two and three out of 7 HCs, respectively. VITT sera markedly activated platelets and this activation was inhibited by both anti-SP and anti-FcγRIIA blocking antibodies. The retrieved thrombus showed positive immunohistochemical labelling of platelets using an anti-SP antibody with reduced ACE2 expression, compared to a thrombus from a pre-pandemic stroke patient. Markers of endothelial dysfunction, NETs and hypercoagulability state were present in VITT sera.Conclusions:
The present data provide first evidence that DNA vaccineencoded Sars-cov-2 SP is detectable in VITT sera (up to several weeks post-vaccination) and in a platelet-rich thrombus, and suggest that SP may contribute to the initial platelet stimulation in VITT patients. Anti-PF4/ polyanion antibodies development could represent an epiphenomenon, which amplifies platelet aggregation, NETosis, and coagulation cascade.
angiotensin converting enzyme 2; blocking antibody; DNA vaccine; endogenous compound; Fc receptor IIa; thrombocyte factor 4; vaxzevria; virus spike protein; adult; adverse drug reaction; blood clotting; case report; cerebrovascular accident; clinical article; conference abstract; endothelial dysfunction; female; gene expression; histopathology; human; human cell; human tissue; hypercoagulability; immunohistochemistry; male; mechanical thrombectomy; middle cerebral artery; NETosis; nonhuman; pandemic; protein expression; protein function; Severe acute respiratory syndrome coronavirus 2; side effect; stroke patient; thrombocyte activation; thrombocyte aggregation; thrombus; vaccination; vaccine-induced immune thrombotic thrombocytopenia
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Topics:
Vaccines
Language:
English
Journal:
European Stroke Journal
Year:
2022
Document Type:
Article
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