![]() ![]() Moreover, organ-protective effect of ACE2 has been well-documented in hypertension, diabetes, atherosclerosis, and acute respiratory distress syndrome 12. Knockout of ACE2 in mice resulted in a reduction in cardiac contractility 11, indicating that ACE2 is an essential regulator of heart function. Furthermore, whether the vaccination in individuals with cardiovascular comorbidities would exaggerate cardiac injury remains unclear, and warrants further experimental and clinical investigation.ĪCE2 is a membrane-localized aminopeptidase that is highly expressed in the heart and blood vessels and has direct effects on multiple organs via counter-regulation of the renin-angiotensin system (RAS), a primary cardiovascular regulatory system 10. Although the causal relationship is yet to be established, and the adverse events following vaccination may not be considered purely caused by the vaccines themselves, it raises concern about cardiac safety of the COVID-19 vaccine. It is worth noting that vaccine-associated acute myocardial infarction and cardiac arrest are more common in individuals aged >75 6, who are theoretically at high risk of cardiovascular diseases. In addition, as worldwide vaccination goes on rapidly, the COVID-19 vaccine has been associated with an elevated risk of several cardiac adverse events (e.g., acute myocardial infarction and cardiac arrest) according to real-world safety data 6, 7, 8, 9. To date, clinical study that evaluating the safety of COVID-19 vaccination in patients with preexisting ischemic heart diseases has not been reported. Although trials of the approved spike-based COVID-19 vaccines have not detected vaccine-related serious adverse events, it should be noticed that safety of these vaccines was mostly evaluated in healthy volunteers, and little is known about their effects on patients with or at risk of chronic diseases 3, 4, 5. 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. An unprecedented number of COVID-19 vaccination campaign are under way worldwide. ![]()
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