Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA.
Stem Cell Reports. 2021 Sep 14;16(9):2274-2288. doi: 10.1016/j.stemcr.2021.07.012. Epub 2021 Jul 20.
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.
高达 20%的 COVID-19 患者出现了心脏损伤，但心肌组织病理学的病因仍不清楚。在这里，我们使用已建立的体内仓鼠模型，证明了 SARS-CoV-2 可以在感染动物的心肌细胞中检测到。此外，我们在感染 SARS-CoV-2 的仓鼠和 COVID-19 尸检样本中发现了受损的心肌细胞。为了探讨其机制，我们发现人类多能干细胞来源的心肌细胞（hPSC 衍生的 CMs）和成年心肌细胞（CMs）均可被 SARS-CoV-2 有效感染，导致单核细胞趋化因子 CCL2 的分泌和随后的单核细胞募集。在感染的仓鼠心脏中也观察到 CCL2 表达增加和单核细胞浸润。尽管受感染的 CMs 受到损伤，但我们发现巨噬细胞的存在显著减少了 SARS-CoV-2 感染的 CMs。总的来说，我们的研究提供了直接证据，表明 SARS-CoV-2 在体内感染了 CMs，并提出了 COVID-19 患者心脏组织中免疫细胞浸润和组织病理学的一种机制。
