There has been an unprecedented rapid response by vaccine developers with now over 167 COVID-19 vaccine candidates in clinical trials and 15 having been approved for at least limited use as of 28 June 2022. Therefore, generating a vaccine encoding/introducing the spike protein is the strategy used by the majority of COVID-19 vaccine candidates, including vaccines based on viral vectors, nanoparticles/virus-like particles, proteins/peptides, RNA, and DNA 2. For cell entry, the SARS-CoV-2 virus majorly binds to the host receptor angiotensin-converting enzyme 2 (ACE2) through its spike glycoprotein, which is the only viral protein that interacts with host cells and is the most diverging protein between different coronaviruses 1. Hence, the development of a safe and effective vaccine that can prevent SARS-CoV-2 infection and transmission has rapidly become top priority. The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by a coronavirus SARS-CoV-2 has spurred an unprecedented public health crisis worldwide. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. Vasa 51, 62–70 10.An unprecedented number of COVID-19 vaccination campaign are under way worldwide. (2022) Endothelial inflammation and dysfunction in COVID-19. Sbirkov Y., Dzharov V., Todorova K., Hayrabedyan S. (2015) Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. (2021) The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease. Circulation 141, 1648–1655 10.1161/CIRCULATIONAHA.120.046941Īvolio E., Carrabba M., Milligan R., Kavanagh Williamson M., Beltrami A.P., Gupta K.et al. (2020) COVID-19 and cardiovascular disease. (2020) COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nishiga M., Wang D.W., Han Y., Lewis D.B. Future studies are needed to determine the effect of the S protein on pericytes in other organs and evaluate the effectiveness of CD147 receptor-blocking therapies to decrease organ damage caused by the S protein.ĬD147 Receptor COVID-19 Pericytes cardiovascular disease virus spike protein. These findings support the notion that circulating SARS-CoV-2 S protein could contribute to cardiovascular disease independent of viral infection. previously determined that the S protein acting through the cluster of differentiation 147 (CD147) receptor, and another unknown mechanism had detrimental effects on human cardiac pericytes (Clin Sci (Lond) (2021) 135 (24): 2667-2689. Experimental findings are demonstrating that the circulating S protein can bind to receptors resulting in inflammation and cell, tissue, and organ damage. Interestingly, the SARS-CoV-2 spike (S) protein can be found circulating in the blood of COVID-19 patients. The SARS-CoV-2 virus that results in COVID-19 has been found to damage multiple organs beyond the lung.
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