Purpose Book Coronavirus disease 2019 (COVID-19), is an acute respiratory stress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Methods A systematic search in the literature was L-685458 performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. Results The aim of the present review was to conclude experimental data and medical observations that linked the pathophysiology mechanisms of inflamm-aging, mild-grade swelling, and cytokine storm in some seniors adults with severe COVID-19 illness. strong class=”kwd-title” Keywords: ACE2 receptor, Autophagy, COVID-19, Cytokine storm, Senescent cell, Vitamin D Intro The COVID-19, now named SARS-CoV2, distributing in Wuhan, China, and now spread globally rapidly . It is reported that COVID-19 has the same viral genome (above 85% identity in the genome), and pathophysiology mechanisms with the SARS-CoV . The COVID-19 illness influencing all age-groups, but it appears to be more severe in seniors adults . It seems that very high pro-inflammatory cytokine release, which is described as cytokine storm, is a pivotal pathophysiological mechanism in elderly COVID-19 patients . Aging relates to increased degrees of systemic pro-inflammatory cytokines and reduced degrees of systemic anti-inflammatory cytokines. Therefore, a chronic condition of swelling may be developed in aged topics, referred to as inflamm-aging [5, 6]. Ample research have indicated raised degrees of interleukin (IL)-6, IL-1, tumor necrosis element- (TNF ), aswell as C-reactive proteins (CRP) in aged topics [7, 8]. Although, the precise underlying system of cytokine surprise in elderly adults with severe COVID-19 infection is far from clear. However, it is likely that dysregulation of the cytokine homeostasis in inflame-aging phenomenon may play a critical role in the risk of a cytokine storm, and subsequently acute respiratory distress syndrome (ARDS) in some elderly patients with severe L-685458 COVID-19 infection. It seems that cytokine storm phenomenon in elderly patients with severe COVID-19 infection, is associated with many age-related pathophysiologic processes, including alteration of angiotensin-converting enzyme 2 (ACE2) receptor expression , excess ROS production , alteration of autophagy , the inflammatory phenotype of senescent cell activity, particularly adipose tissue , and immune-senescence , as well as lack of vitamin D content . Here, we are going to review and discuss all above mentioned age-related pathophysiological pathways that appear to contribute to the dysregulation of cytokine networks and possibly a cytokine storm in elderly patients with severe COVID-19 infection. The possible pathophysiology of COVID-19 infection It has been shown that COVID-19 infection has distinctive behavior among elderly adults (severe infection) as compared with children and young adults (none or mild infection). Indeed, COVID-19 infection can induce severe infection, including pneumonia and ARDS in some elderly adults or sick patients, and not in children or young adults . What is the reason that the deadly cases of COVID-19 mainly seen in elderly patients? Here, first we are going to review and compare the possible pathophysiology mechanisms of mild infection and severe infection in young and elderly adults with COVID-19, respectively. Normal immunologic responses in young adults with mild COVID-19 infection Despite increasing evidences on the immune response to pathogens, however, less is known about the exact immunologic mechanism TNFRSF9 of COVID-19 infections. As shown in Fig.?1, initiation from the defense response against invading coronavirus starts with a primary disease L-685458 from the bronchiole and bronchi epithelium. Initial, antigen-independent innate immunity supplies the first type of leukocytes protection against microorganisms. Innate immune system protection involves many cell types, including leukocytes such as for example neutrophils, eosinophils, basophils, monocytes, macrophages, lung epithelial cells, mast cells, organic killer (NK cells) . Pursuing initial COVID-19 disease, lung-resident dendritic cells (DCs) become triggered and modification to antigen-presenting cells (APCs). Certainly, APCs will be the first type of.