Key result
Spike protein-conditioned immune cells suppress cardiomyocyte viability, whereas direct spike exposure shows no toxicity.
Why the study?
SARS-CoV-2 infection is associated with cardiac injury, but whether this injury results mainly from direct viral infection or is secondary to a SARS-CoV-2-induced cytokine storm remained unclear.
Does SARS-CoV-2 S protein injure cardiomyocytes directly or indirectly through S protein-triggered cytokine release?
Does SARS-CoV-2 S protein injure cardiomyocytes directly or indirectly through S protein-triggered cytokine release?
SARS-CoV-2-induced cardiac injury appears to be mediated primarily by S protein-triggered host immune/cytokine responses rather than direct S protein toxicity on cardiomyocytes, suggesting COVID-19 treatment strategies should address both viral replication and immune over-activation.
Answers are grounded in this paper and cite their sources.
May implicate cytokine storm over direct S protein effects; leaves open clinical relevance in SARS-CoV-2 cardiac injury.
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.
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Chang et al. (2021) studied SARS-CoV-2-associated cardiac injury. S protein-derived human T lymphocyte / peripheral blood mononuclear cell conditioned medium vs. Direct treatment with SARS-CoV-2 S protein was evaluated on Cardiomyocyte injury (cell apoptosis and viability). Supernatant medium of S protein pre-conditioned PBMCs significantly suppressed cardiomyocyte viability, whereas direct S protein treatment did not increase cell apoptosis.
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