@article{4830ab72efd74fc19d3728037df7370a,
title = "Cardiomyocytes recruit monocytes upon SARS-CoV-2 infection by secreting CCL2",
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",
author = "Liuliu Yang and Nilsson-Payant, {Benjamin E.} and Yuling Han and Fabrice Jaffr{\'e} and Jiajun Zhu and Pengfei Wang and Tuo Zhang and David Redmond and Sean Houghton and Rasmus M{\o}ller and Daisy Hoagland and Lucia Carrau and Shu Horiuchi and Marisa Goff and Lim, {Jean K.} and Yaron Bram and Chanel Richardson and Vasuretha Chandar and Alain Borczuk and Yaoxing Huang and Jenny Xiang and Ho, {David D.} and Schwartz, {Robert E.} and tenOever, {Benjamin R.} and Todd Evans and Shuibing Chen",
note = "Funding Information: This work was supported by the American Heart Association (18CSA34080171 to S.C. and T.E.), NIDDK (R01DK130454, R01DK116075, R01DK119667, R01DK119667-02S1, R01 DK124463, and U01 DK127777, S.C.), American Diabetes Association (7-20-COVID-211 to S.C.), Department of Surgery , Weill Cornell Medicine (to T.E. and S.C.), Bill and Melinda Gates Foundation (S.C., T.E., R.E.S, B.tO,) and ( NCI R01CA234614 , NIAID 2R01AI107301 and NIDDK R01DK121072 and 1RO3DK117252 ), Department of Medicine, Weill Cornell Medicine (to R.E.S.), by the Defense Advanced Research Projects Agency ( DARPA-16-35-INTERCEPT-FP-006 to B.T.), and by the Jack Ma Foundation (to D.D.H.). S.C. and R.E.S. are supported as Irma Hirschl Trust Research Award Scholars. T.E. is supported by an Outstanding Investigator Award from the NHLBI ( R35 HL135778 ). R.M. is supported by American Heart Association grant #833781. Y.H. is a NYSTEM Stem Cell Biology Scholar. Funding Information: This work was supported by the American Heart Association (18CSA34080171 to S.C. and T.E.), NIDDK (R01DK130454, R01DK116075, R01DK119667, R01DK119667-02S1, R01 DK124463, and U01 DK127777, S.C.), American Diabetes Association (7-20-COVID-211 to S.C.), Department of Surgery, Weill Cornell Medicine (to T.E. and S.C.), Bill and Melinda Gates Foundation (S.C. T.E. R.E.S, B.tO,) and (NCI R01CA234614, NIAID 2R01AI107301 and NIDDK R01DK121072 and 1RO3DK117252), Department of Medicine, Weill Cornell Medicine (to R.E.S.), by the Defense Advanced Research Projects Agency (DARPA-16-35-INTERCEPT-FP-006 to B.T.), and by the Jack Ma Foundation (to D.D.H.). S.C. and R.E.S. are supported as Irma Hirschl Trust Research Award Scholars. T.E. is supported by an Outstanding Investigator Award from the NHLBI (R35 HL135778). R.M. is supported by American Heart Association grant #833781. Y.H. is a NYSTEM Stem Cell Biology Scholar. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = sep,
day = "14",
doi = "10.1016/j.stemcr.2021.07.012",
language = "English",
volume = "16",
pages = "2274--2288",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "9",
}