Is there a role for the ACE2 receptor in SARS-CoV-2 interactions with platelets?

J Thromb Haemost. 2021 Jan;19(1):46-50. doi: 10.1111/jth.15156. Epub 2020 Nov 18.


There is an urgent need to understand the underlying mechanisms contributing to thrombotic and inflammatory complications during COVID-19. Data from independent groups have identified that platelets are hyperreactive during COVID-19. Platelet hyperreactivity is accompanied by changes in platelet gene expression, and enhanced interactions between platelets and leukocytes. In some patients, SARS-CoV-2 mRNA has been detected in platelets. Together, this suggests that SARS-CoV-2 may interact with platelets. However, controversy remains on which receptors mediate SARS-CoV-2 platelet interactions. Most, but not all, transcriptomic and proteomic analyses fail to observe the putative SARS-CoV-2 receptor, angiotensin converting enzyme-2, or the cellular serine protease necessary for viral entry, TMPRSS2, on platelets and megakaryocytes. Interestingly, platelets express other known SARS-CoV-2 receptors, which induce similar patterns of activation to those observed when platelets are incubated with SARS-CoV-2. This article explores these findings and discusses ongoing areas of controversy and uncertainty with regard to SARS-CoV-2 platelet interactions.

Keywords: ACE2; COVID-19; SARS-CoV-2; platelets; thrombosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / blood*
  • Angiotensin-Converting Enzyme 2 / physiology
  • Blood Platelets / virology*
  • COVID-19 / blood*
  • COVID-19 / complications
  • COVID-19 / virology*
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / physiology
  • Humans
  • Megakaryocytes / virology
  • Models, Biological
  • Platelet Activation
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Receptors, Virus / blood*
  • Receptors, Virus / physiology
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / pathogenicity*
  • SARS-CoV-2 / physiology*
  • Serine Endopeptidases / blood
  • Serine Endopeptidases / physiology
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / virology
  • Virus Internalization


  • RNA, Viral
  • Receptors, Virus
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human