Wei-Ting Chang1,2,3, Yu-Wen Lin1, Zhih-Cherng Chen1, Ping-Yen Liu1,4. 1. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University. 2. Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center. 3. Department of Biotechnology, Southern Taiwan University of Science and Technology. 4. Division of Cardiology, Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Abstract
BACKGROUND: Emerging evidence has shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with cardiac injury, but it remains unclear whether cardiac injury is mainly caused by direct viral infection or is secondary to SARS-CoV-2-induced cytokine storm. METHODS: Through directly treating cardiomyocytes with S protein, a crucial surface protein of SARS-CoV-2, and indirectly treating cardiomyocytes with S protein-derived human T lymphocyte conditioned medium, we compared the intensities of cardiomyocyte injuries caused by either S protein of the virus or S protein of virus-triggered cytokines. RESULTS: The directly treated cardiomyocytes did not show increasing cell apoptosis. In contrast, cardiomyocytes treated with the supernatant medium of S protein pre-conditioned peripheral blood mononuclear cells showed significantly suppressed viability. In addition, using a cardiovascular disease-specific PCR array, genes associated with hypertrophy, apoptosis, inflammation and angiogenesis were observed to be affected by cytokine stress. CONCLUSIONS: Collectively, we found that SARS-CoV-2-induced heart injury may be mainly through the S protein of the virus enhancing host immune responses instead of the S protein of the virus per se. With regards to clinical application, the strategy for treating COVID-19 should not only focus on anti-viral therapy but also on suppressing over-activated immunity.
BACKGROUND: Emerging evidence has shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with cardiac injury, but it remains unclear whether cardiac injury is mainly caused by direct viral infection or is secondary to SARS-CoV-2-induced cytokine storm. METHODS: Through directly treating cardiomyocytes with S protein, a crucial surface protein of SARS-CoV-2, and indirectly treating cardiomyocytes with S protein-derived human T lymphocyte conditioned medium, we compared the intensities of cardiomyocyte injuries caused by either S protein of the virus or S protein of virus-triggered cytokines. RESULTS: The directly treated cardiomyocytes did not show increasing cell apoptosis. In contrast, cardiomyocytes treated with the supernatant medium of S protein pre-conditioned peripheral blood mononuclear cells showed significantly suppressed viability. In addition, using a cardiovascular disease-specific PCR array, genes associated with hypertrophy, apoptosis, inflammation and angiogenesis were observed to be affected by cytokine stress. CONCLUSIONS: Collectively, we found that SARS-CoV-2-induced heart injury may be mainly through the S protein of the virus enhancing host immune responses instead of the S protein of the virus per se. With regards to clinical application, the strategy for treating COVID-19 should not only focus on anti-viral therapy but also on suppressing over-activated immunity.
Entities:
Keywords:
Cardiac injury; Cytokine; S protein; SARS-CoV-2
Authors: Kevin J Clerkin; Justin A Fried; Jayant Raikhelkar; Gabriel Sayer; Jan M Griffin; Amirali Masoumi; Sneha S Jain; Daniel Burkhoff; Deepa Kumaraiah; LeRoy Rabbani; Allan Schwartz; Nir Uriel Journal: Circulation Date: 2020-03-21 Impact factor: 29.690