Evidence map›Paper›PMID 34280256›Full record

ArticleBlood2021

Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.

Andreas Greinacher, Kathleen Selleng, Julia Mayerle, Raghavendra Palankar, Jan Wesche, Sven Reiche, Andrea Aebischer, Theodore E Warkentin, Maximilian Muenchhoff, Johannes C Hellmuth and 17 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
23.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
  2. Article
  3. Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023
    Review

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 11 institutions in 4 countries.

Andreas GreinacherInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.ORCID 0000-0001-8343-7336
Kathleen SellengInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.
Julia MayerleDepartment of Medicine II, University Hospital Munich, and German Centre for Infection Research (DZIF) (partner site Munich), Munich, Germany.ORCID 0000-0002-3666-6459
Raghavendra PalankarInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.ORCID 0000-0002-8957-1103
Jan WescheInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.ORCID 0000-0001-5025-7355
Sven ReicheDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler Institut, Greifswald, Germany.
Andrea AebischerDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler Institut, Greifswald, Germany.
Theodore E WarkentinDepartment of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, ON, Canada.ORCID 0000-0002-8046-7588
Maximilian MuenchhoffMax von Pettenkofer Institute, Virology, Ludwig Maximilians University of Munich, and DZIF, Munich, Germany.ORCID 0000-0001-7016-0470
Johannes C HellmuthDepartment of Medicine III, University Hospital Munich, Munich, Germany.ORCID 0000-0001-8409-3037
Oliver T KepplerMax von Pettenkofer Institute, Virology, Ludwig Maximilians University of Munich, and DZIF, Munich, Germany.
Daniel DuerschmiedHeart Center Freiburg University, Cardiology and Angiology I and Medical Intensive Care, Medical Center.ORCID 0000-0001-5249-4012
Achim LotherHeart Center Freiburg University, Cardiology and Angiology I and Medical Intensive Care, Medical Center.ORCID 0000-0001-9107-5558
Siegbert RiegDivision of Infectious Diseases, Department of Medicine II, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.ORCID 0000-0001-7493-7080
Meinrad Paul GawazDepartment of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
Karin Anne Lydia MuellerDepartment of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
Christian S ScheerDepartment of Anesthesiology and Intensive Care Medicine, and.ORCID 0000-0001-6171-8874
Matthias NappDepartment of Anesthesiology and Intensive Care Medicine, and.
Klaus HahnenkampDepartment of Anesthesiology and Intensive Care Medicine, and.
Guglielmo LuccheseDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany.
Antje VogelgesangDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany.
Agnes FlöelDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany.
Piero LovreglioInterdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy; and.
Angela StufanoInterdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy; and.
Rolf MarschalekInstitute of Pharmacology Biology, Biocenter, Goethe University, Frankfurt am Main, Germany.ORCID 0000-0003-4870-3445
Thomas ThieleInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.
Immune-Response in COVID-19 Vaccination Study Group
Universitätsmedizin Greifswald · DEFriedrich-Loeffler-Institut · DELudwig-Maximilians-Universität München · DEUniversity Medical Center Freiburg · DEUniversity of Bari Aldo Moro · ITUniversity of Tübingen · DEGerman Center for Infection Research · DEGoethe University Frankfurt · DEMcMaster University · CAMünchen Klinik · DEUniversity of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.

Indexed as

AdultAgedAged, 80 and overAntibodiesBlood PlateletsCohort StudiesCOVID-19COVID-19 VaccinesCross ReactionsEpitopesFemaleHeparinHumansImmunoglobulin GMaleMiddle AgedAntibodiesCOVID-19 VaccinesEpitopesHeparinImmunoglobulin GPlatelet Factor 4Spike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID34280256
PMCPMC8294553
OpenAlexW3183590901

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.