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Record W3155275345 · doi:10.21203/rs.3.rs-404769/v1

Anti-SARS-CoV-2 Spike Protein and Anti-Platelet Factor 4 Antibody Responses Induced by COVID-19 Disease and ChAdOx1 nCov-19 vaccination

2021· preprint· en· W3155275345 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueResearch Square · 2021
Typepreprint
Languageen
FieldMedicine
TopicHeparin-Induced Thrombocytopenia and Thrombosis
Canadian institutionsMcMaster University
FundersUniversität GreifswaldBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftWilhelm Sander-StiftungEuropean CommissionDeutsches Zentrum für InfektionsforschungAustralian Government
KeywordsPlatelet factor 4HeparinAntibodyPlatelet activationEpitopeRecombinant DNAHeparin-induced thrombocytopeniaImmunologyVirologyMedicineVaccinationPlateletBiologyInternal medicineGeneBiochemistry

Abstract

fetched live from OpenAlex

<title>Abstract</title> <bold>Background</bold>: Some recipients of ChAdOx1 nCoV-19 COVID-19 Vaccine AstraZeneca develop antibody-mediated vaccine-induced thrombotic thrombocytopenia (VITT), associated with cerebral venous and other unusual thrombosis resembling autoimmune heparin-induced thrombocytopenia. A prothrombotic predisposition is also observed in Covid-19. We explored whether antibodies against the SARS-CoV-2 spike protein induced by Covid-19 cross-react with platelet factor 4 (PF4/CXLC4), the protein targeted in both VITT and autoimmune heparin-induced thrombocytopenia.<bold>Methods</bold>: Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared via prediction tools and 3D modelling software (IMED, SIM, MacMYPOL). Sera from 222 PCR-confirmed Covid-19 patients from five European centers were tested by PF4/heparin ELISA, heparin-dependent and PF4-dependent platelet activation assays. Immunogenic reactivity of purified anti-PF4 and anti-PF4/heparin antibodies from patients with VITT were tested against recombinant SARS-CoV-2 spike protein. <bold>Results</bold>: Three motifs within the spike protein sequence share a potential immunogenic epitope with PF4. Nineteen of 222 (8.6%) Covid-19 patient sera tested positive in the IgG-specific PF4/heparin ELISA, none of which showed platelet activation in the heparin-dependent activation assay, including 10 (4.5%) of the 222 Covid-19 patients who developed thromboembolic complications. Purified anti-PF4 and anti-PF4/heparin antibodies from two VITT patients did not show cross-reactivity to recombinant SARS-CoV-2 spike protein. <bold>Conclusions</bold>: The antibody responses to PF4 in SARS-CoV-2 infection and after vaccination with COVID-19 Vaccine AstraZeneca differ. Antibodies against SARS-CoV-2 spike protein do not cross-react with PF4 or PF4/heparin complexes through molecular mimicry. These findings make it very unlikely that the intended vaccine-induced immune response against SARS-CoV-2 spike protein would itself induce VITT.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.007
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.670
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.007
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.002
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.150
GPT teacher head0.464
Teacher spread0.313 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it