No Correlation between Anti-PF4 and Anti-SARS-CoV-2 Antibodies after ChAdOx1 nCoV-19 Vaccination.
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ABSTRACT:
SUBMITTER: Uzun G
PROVIDER: S-EPMC8427534 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
Publications
No Correlation between Anti-PF4 and Anti-SARS-CoV-2 Antibodies after ChAdOx1 nCoV-19 Vaccination.
Uzun Günalp G Althaus Karina K Bakchoul Tamam T
The New England journal of medicine 20210825 14
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Project description:BackgroundThe mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity.MethodsWe report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.ResultsIn the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.ConclusionsVaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.
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Project description:Comprehensive assessment of SARS-CoV-2 antibodies against antigenic epitopes and cross-neutralization on variants is essential to monitor after infection or vaccination. From 32 COVID-19 patients and 40 vaccinated individuals [20 Oxford-AstraZeneca (AZ) and 20 Pfizer-BioNTech (BNT)], 348 serial sera are collected until 40 days after infection and 3 months after homologous booster vaccination. Antibody levels were monitored using a multiplex-bead assay including variant spike antigens, Roche (S1/RBD total) and a surrogate virus neutralization test (GenScript). Anti-S/S1/RBD levels were higher than anti-S2/N levels from 2 weeks after infection and were higher in severe infection (P < 0.05). Vaccination showed highest antibody levels after 1-month booster and had consistently high levels in the order of anti-full S, anti-RBD, anti-S1 and anti-S2. Infection induced higher anti-S2/N levels than prime vaccination (P < 0.05). Three months after BNT/BNT vaccination, antibody levels against S1/RBD and 23 variant antigens were higher than post-infection or AZ groups (P < 0.05). Regarding intraindividual changes from post-prime to post-boost vaccination, boost induced a 1.1- to 3.9-fold increase on multiplex-bead assay, 22.8- to 24.2-fold on Roche assay and 22.8- to 24.2-fold on GenScript assay. Post-prime levels by multiplex-bead assay predicted post-boost levels, but Roche and GenScript results were not predictive in the AZ group. The kinetics of SARS-CoV-2 antibody levels vary depending on the antigenic epitopes, assay kit, disease severity or vaccine type. Assessing seroconversion using multiplex-bead assays may contribute to monitoring the disease course, adjusting vaccination strategies, and accelerating vaccination efficacy.
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Project description:BackgroundSeveral cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder.MethodsWe assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay.ResultsOf the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation.ConclusionsVaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).
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