Cardiomyocytes infected with SARS-CoV2 recruit immune cells

Sayak Banerjee, Amity University Kolkata

The current Coronavirus Disease 2019 (COVID-19) pandemic is caused by the beta coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides the most prevalent consequences of respiratory failure, cardiac involvement (heart diseases caused due to SARS-CoV-2 infection in the heart tissue) is a common outcome that is observed in hospitalized COVID-19 patients.

It was found in one of the Wuhan units that 7% of total patients and 22% of critically ill patients suffered a myocardial injury. This was associated with poor prognosis and was evident by an increased amount of cardiac biomarkers. This included many COVID-19 affected children suffering from cardiac dysfunction as well as adults suffering from myocarditis.

Studies involving cardiac damage due to SARS-CoV-2:

The mortality risk concerning acute cardiac injury was more significant than age-related chronic pulmonary disease or earlier history of cardiovascular disease. It was hypothesized that the cause of these cardiac injuries could probably entail increased cardiac stress. Moreover, the cardiac stress could be due to direct myocardial infarction by SARS-CoV-2, respiratory failure, and hypoxemia, or indirect cardiotoxicity from a systemic inflammatory response. Many scientists have identified the presence of SARS-CoV-2 RNA in autopsy samples from the hearts of COVID-19 patients. 

It was controversial whether cardiomyocytes (CMs) are directly infected by SARS-CoV-2 in patients. It was said that immune cells could be involved in the potential mechanism of cardiac damage. This is because abnormal inflammatory infiltrates were constantly being detected in the heart samples. Recently, a research team from Weill Cornell Medical College in New York has reported SARS-CoV-2 infection in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in vitro. Generally, the collection of heart biopsies from COVID-19 patients during or after acute infection is accompanied by several inherent challenges. Hence, they had undergone a systematic examination of the heart tissues of SARS-CoV-2 infected Syrian hamsters.

Findings from the Hamster model:

Using intranasally infected hamsters, the scientists detected the expression of viral proteins in the cardiomyocytes (CMs). This gave evidence that the infection of CMs resulted from the intranasal exposure of SARS-CoV-2. The macrophages recruited to the heart release certain monocyte chemoattractant cytokine CCL2 might cause hyper-inflammation, hypoxemia, and respiratory failure. These mechanisms could additionally contribute to the heart damage observed in COVID-19 patients. On examining, they observed that there is an overexpression of CCL2 in SARS-CoV-2 infected cells and COVID-19 patient lung autopsy samples. SARS-CoV-2 infected CMs were found to express higher levels of CCL2 than non-infected cells in the hamster model. 

They employed a transwell platform to exhibit that hPSC-derived CMs or adult human CMs infected with SARS-CoV-2 engage monocytes. This observation confirmed the prior reports of abnormal macrophage infiltration in the hearts of COVID-19 patients. Their data conveyed that the increase in macrophage recruitment leads to a decrease in SARS-CoV-2 infected CMs due to enhanced apoptosis. This macrophage infiltration could induce the secretion of Reactive oxygen species (ROS), inflammatory cytokines, and cause CM damage. Conversely, in the absence of SARS-CoV-2, the survival of CM is unaffected by the presence of macrophages. The upregulation of ROS in the hearts of infected hamsters implied that macrophage recruitment gives rise to immune-mediated CM inflammatory damage in COVID-19 patients.

Contribution to cardiac pathophysiology:

The researchers concluded that both the recruitment of immune cells and direct CM infection might balance cardiac pathophysiology in COVID-19 patients. Nevertheless, other types of cells in hearts can also be infected by SARS-CoV-2 and give rise to the recruitment of mononuclear cells. Therefore, the research team reported the confirmation of SARS-CoV-2 infection of cardiomyocytes in vivo. They also demonstrated an in vitro model to study the infiltration of immune cells and pathophysiology in heart tissues of COVID-19 patients.

Also read: Biosensors for detection of SARS-CoV-2 infection

Reference:

1. Yang, L., Nilsson-Payant, B. E., Han, Y., Jaffré, F., Zhu, J., Wang, P., Zhang, T., Redmond, D., Houghton, S., Møller, R., Carrau, L., Horiuchi, S., Goff, M., Lim, J. K., Bram, Y., Richardson, C., Chandar, V., Alain Borczuk, Huang, Y., … Chen, S. (2021). Cardiomyocytes recruit monocytes upon sars-cov-2 infection by secreting ccl2. Stem Cell Reports, S2213671121003787. https://doi.org/10.1016/j.stemcr.2021.07.012

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Author info:

Sayak Banerjee is a 3^rd year Biotechnology Engineering Student with great interest in Immunology and Molecular genetics. He is a creative scientific writer in BioXone with an inclination towards gaining knowledge regarding vast sections of Biotechnology and emphasizing himself in various wet lab skills.

Publications: 

• https://bioxone.in/news/worldnews/car-t-cells-scientists-discover-on-off-switches-for-cell-immunotherapy/
• https://bioxone.in/news/worldnews/neutrophil-derived-nanovesicles-a-novel-drug-delivery-system/
• https://bioxone.in/news/worldnews/pig-to-human-heart-transplantation-a-solution-to-the-rarity-of-donor-organs/