Coagulopathies after Vaccination against SARS-CoV-2 May Be Derived from a Combined Effect of SARS-CoV-2 Spike Protein and Adenovirus Vector-Triggered Signaling Pathways

Int J Mol Sci. 2021 Oct 6;22(19):10791. doi: 10.3390/ijms221910791.


Novel coronavirus SARS-CoV-2 has resulted in a global pandemic with worldwide 6-digit infection rates and thousands of death tolls daily. Enormous efforts are undertaken to achieve high coverage of immunization to reach herd immunity in order to stop the spread of SARS-CoV-2 infection. Several SARS-CoV-2 vaccines based on mRNA, viral vectors, or inactivated SARS-CoV-2 virus have been approved and are being applied worldwide. However, the recent increased numbers of normally very rare types of thromboses associated with thrombocytopenia have been reported, particularly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The statistical prevalence of these side effects seems to correlate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the exact molecular mechanisms are still not clear. The present review summarizes current data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis indicating that coagulopathies, including thromboses, thrombocytopenia, and other related side effects, are correlated to an interplay of the two components in the vaccine, i.e., the spike antigen and the adenoviral vector, with the innate and immune systems, which under certain circumstances can imitate the picture of a limited COVID-19 pathological picture.

Keywords: COVID-19; NF-kappaB; SARS-CoV-2; adenoviral vector; platelet factor 4 (PF4); spike protein; thrombocytopenia; thrombosis; vaccination; vaccine-induced immune thrombotic thrombocytopenia (VITT).

Publication types

  • Review

MeSH terms

  • Adenoviridae / immunology
  • Animals
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / adverse effects*
  • COVID-19 Vaccines / immunology
  • ChAdOx1 nCoV-19
  • Genetic Vectors / adverse effects
  • Genetic Vectors / immunology
  • Humans
  • Purpura, Thrombocytopenic, Idiopathic / etiology
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / adverse effects
  • Spike Glycoprotein, Coronavirus / immunology*
  • Thrombocytopenia / etiology*
  • Thrombocytopenia / immunology
  • Thrombosis / etiology*
  • Thrombosis / immunology
  • Vaccination / adverse effects


  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ChAdOx1 nCoV-19