Abstract
Aims: Patients with severe respiratory syndrome caused by SARS-CoV-2 undergo cardiac complications due to hyper-inflammatory conditions. Although the presence of the virus has been detected in the myocardium of infected patients, and infection of induced pluripotent cell-derived cardiomyocytes has been demonstrated, the reported expression of Angiotensin-Converting Enzyme-2 (ACE2) in cardiac stromal cells suggests that SARS-CoV-2 may determine cardiac injury by sustaining productive infection and increasing inflammation.
Methods and results: We analysed expression of ACE2 receptor in primary human cardiac stromal cells derived from cardiospheres, using proteomics and transcriptomics before exposing them to SARS-CoV-2 in vitro. Using conventional and high sensitivity PCR methods, we measured virus release in the cellular supernatants and monitored the intracellular viral bioprocessing. We performed high-resolution imaging to show the sites of intracellular viral production and demonstrated the presence of viral particles in the cells with electron microscopy. We finally used RT-qPCR assays to detect genes linked to innate immunity and fibrotic pathways coherently regulated in cells after exposure to the virus.
Conclusions: Our findings indicate that cardiac stromal cells are susceptible to SARS-CoV-2 infection and produce variable viral yields depending on the extent of cellular ACE2 receptor expression. Interestingly, these cells also evolved towards hyper-inflammatory/pro-fibrotic phenotypes independently of ACE2 levels. Thus, SARS-CoV-2 infection of myocardial stromal cells could be involved in cardiac injury and explain the high number of complications observed in severe cases of COVID-19.
Keywords: ACE2; Cardiac stromal cells; Fibrosis; Infection; Inflammation; SARS-CoV-2.
【저자키워드】 SARS-CoV-2, Inflammation, ACE2, Infection, fibrosis, Cardiac stromal cells, 【초록키워드】 COVID-19, SARS-CoV-2, proteomics, Innate immunity, SARS-COV-2 infection, transcriptomics, ACE2 receptor, fibrosis, in vitro, virus, cardiac injury, sensitivity, electron microscopy, PCR, Microscopy, pathway, severe cases, Complication, phenotype, angiotensin-converting enzyme-2, expression, Angiotensin-converting enzyme, cellular, cardiac, angiotensin, Injury, Viral particles, High-resolution, RT-qPCR assay, Cardiac complications, exposure to, stromal cells, stromal cell, Myocardium, cardiac complication, infected patients, These cells, RT-qPCR assays, Severe case, severe respiratory syndrome, supernatant, viral particle, susceptible, Myocardial, Cell, performed, detect, caused, involved, reported, analysed, undergo, determine, demonstrated, regulated, conditions, explain, these cell, 【제목키워드】 SARS-CoV-2, Human, phenotype, expression, stromal cell, viral particle, infective,