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With rapid spread of severe acute respiratory syndrome- corona virus-2 (SARS-COV-2) globally, some new aspects of the disease have been reported. Recently, it has been reported the incidence of Kawasaki-like disease among children with COVID-19. Since, children had been known to be less severely affected by the virus in part due to the higher concentration of Angiotensin converting enzyme (ACE)-2 receptor, this presentation has emerged concerns regarding the infection of children with SARS-COV2. ACE2 has anti-inflammatory, anti-fibrotic and anti-proliferative characteristics through converting angiotensin (Ag)-II to Ang (1–7). ACE2 receptor is downregulated by the SARS-COV through the spike protein of SARS-CoV (SARS-S) via a process that is tightly coupled with Tumor necrosis factor (TNF)-α production. TNF-α plays a key role in aneurysmal formation of coronary arteries in Kawasaki disease (KD). Affected children by COVID-19 with genetically-susceptible to KD might have genetically under-expression of ACE2 receptor that might further decrease the expression of ACE2 due to the downregulation of the receptor by the virus in these patients. It appears that TNF- α might be the cause and the consequence of the ACE2 receptor downregulation which results in arterial walls aneurysm. Conclusion: Genetically under-expression of ACE2 receptor in children with genetically-susceptible to KD who are infected with SARS-CoV-2 possibly further downregulates the ACE2 expression by TNF-α and leads to surge of inflammation including TNF-α and progression to Kawasaki-like disease.

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Vaccination against atherosclerosis as a potential effective approach has been under investigation for more than 20 years. Different antigens have been tested in animals with a great success. Lipid-related antigens like Ox-LDL, PCSK9, non-lipid related antigens like interleukins, HSPs β2GPI, DNA vaccination and whole cell vaccination are some examples of successful examinations in animals. Plant-based vaccination which has some advantages over traditional methods has been attracted the scientists´ attention recently. Despite the very substantial struggles and promising results during these years, vaccination against atherosclerosis could not be utilized for the treatment of atherosclerosis in human in part due to the lack of clinical trials to access its safety and efficacy. In fact, designing clinical trials with a sufficient number of participants together with a sufficient duration of follow up to explore the influence of vaccine on the prevention and treatment of atherosclerosis seems to be an imperative requisiteness. It looks investing on clinical trials must be a priority to achieve a clear sight regarding the new, tempting, and promising strategy for vaccination against atherosclerosis.

There have always been challenges concerning tackling knowledge to practice. It is estimated that 85% of the investment in health research are wasted. Due to low quality, not all systematic review and meta-analysis are placed at the top of the hierarchy of evidence. Many individual clinical trials do not have the essential standards; therefore, conducting systematic reviews based on these low-quality individual studies is unreliable as they cannot be applied in healthcare decision-making and lead to resource waste. To overcome this great issue, several organizations have been worked hard to improve data extraction from only well-developed individual studies. However, it is not sufficient. It is time to stop and look back all years behind. It is time to reconsider our efforts to make the best conclusion in order to prohibit the huge waste of energy, time, and resources. The old viewpoint “the Beginning from the End” must be replaced with the new one “the Beginning from the Beginning”.  It means, we must do all struggles to conduct clinical trials in a standard high-quality format from the beginning as much as we could. Although, it does not seem easy, it might be possible by funding a high discipline, well-respected organization that is engaged in this critical issue. The supposed organization must define standards, flexible criteria for clinical trials, and all investigators must perform clinical trials under the supervision of this organization. Providing a considerable financial resource to grant the researches of the low- and middle-income countries to do clinical trials based on the designed protocol, considering an independent, high discipline journal for publishing well-conducted clinical trials regardless of their results, teaching researchers, considering another efficient policy to rank the journals rather than “impact factor” could help achieve this far-reach goal.