Cardiomyocytes recruit monocytes upon SARS-CoV-2 infection by secreting CCL2

Stem Cell Reports. 2021 Sep 14;16(9):2274-2288. doi: 10.1016/j.stemcr.2021.07.012. Epub 2021 Jul 20.

Abstract

Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. Here, using an established in vivo hamster model, we demonstrate that SARS-CoV-2 can be detected in cardiomyocytes of infected animals. Furthermore, we found damaged cardiomyocytes in hamsters and COVID-19 autopsy samples. To explore the mechanism, we show that both human pluripotent stem cell-derived cardiomyocytes (hPSC-derived CMs) and adult cardiomyocytes (CMs) can be productively infected by SARS-CoV-2, leading to secretion of the monocyte chemoattractant cytokine CCL2 and subsequent monocyte recruitment. Increased CCL2 expression and monocyte infiltration was also observed in the hearts of infected hamsters. Although infected CMs suffer damage, we find that the presence of macrophages significantly reduces SARS-CoV-2-infected CMs. Overall, our study provides direct evidence that SARS-CoV-2 infects CMs in vivo and suggests a mechanism of immune cell infiltration and histopathology in heart tissues of COVID-19 patients.

Keywords: CCL2; COVID-19; cardiomyocyte; hPSC; hamster; immune cell infiltration.

Publication types

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

MeSH terms

  • Animals
  • COVID-19 / pathology*
  • Cell Communication / physiology
  • Cell Line
  • Chemokine CCL2 / metabolism*
  • Chlorocebus aethiops
  • Cricetinae
  • Disease Models, Animal
  • Heart Injuries / virology*
  • Humans
  • Macrophages / immunology
  • Male
  • Monocytes / immunology*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / virology
  • Pluripotent Stem Cells / cytology
  • Vero Cells

Substances

  • CCL2 protein, human
  • Chemokine CCL2