SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19

Biosci Rep. 2021 Aug 27;41(8):BSR20210611. doi: 10.1042/BSR20210611.


Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients. Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet-poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.

Keywords: COVID-19; Fibrin(ogen); Microclot; Spike protein Sa; electron microscopy; fluorescence microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyloid / metabolism
  • Blood Platelets / metabolism
  • COVID-19 / pathology*
  • Complement C3 / metabolism
  • Female
  • Fibrin / metabolism*
  • Fibrinogen / metabolism
  • Fibrinolysis / physiology*
  • Humans
  • Lung / pathology
  • Male
  • Microfluidic Analytical Techniques
  • Middle Aged
  • Prothrombin / metabolism
  • SARS-CoV-2 / metabolism
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Thrombosis / pathology*
  • Thrombosis / virology
  • Trypsin / metabolism


  • Amyloid
  • Complement C3
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Prothrombin
  • Fibrin
  • Fibrinogen
  • Trypsin