Cytokines constitute a group of signaling molecules that are consist of peptides with play an essential function in modulating multiple biological functions through their interaction to receptors on the cell surface (Bartee and McFadden,2013). As a defense reaction to stress-generating endogenous events such as cancer or microbial infection (O'Neill, 2015; Vabret et al., 2020). The essential function of the macrophages as being guardians part of the natural immune, facilitating the transformation coming from natural toward adaptive immune, is contingent upon an assortment of cytokines (Arango Duque and Descoteaux,2014), During COVID-19 infection can attack alveolar macrophages and epithelial cells in the alveoli which stimulates cells infected to release chemokines and cytokines (Fehr and Perlman,2015).

Other studies also reported that the COVID-19 severity is corresponding with an increased level of secreted chemokines and cytokines such as interleukin (IL)-2, IL 7, IL-10, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), protein monocyte chemoattractant 1 (MCP1; also known as CCL2), macrophage inflammatory protein 1 alpha (MIP1α; also known as CCL3), ligand CXC-chemokine 10 (CXCL10), C-reactive protein, ferritin, and D-dimers in blood when infected with SARS-CoV-2 (Liu et al., 2020b ; Zhu et al., 2020).

Multiple studies described that a weak and inappropriate response immunity to SARS-CoV-2 appears more frequently in the person infected by other diseases, therefore this may lead to the multiplication of the virus and the occurrence of complications that lead the patient towards severe cases of the disease by excessive recruitment of the human immunological response (Blanco-Melo et al., 2020).

Although SARS-CoV-2 led to a pandemic of coronavirus disease in 2019, so the world became in a fierce confrontation against the virus through the development of new treatment methods (Huang et al., 2020a). One of the most prominent methods used in confronting the virus, which determines the severity of the disease, is the excessive immune response through excessive secretion of the cytokines in addition chemokines, which referred to as "cytokine storm syndrome."(CSS) (Mehta et al., 2020).

Also, cytokine production in patients with COVID-19 was found to be imbalanced with regard to controlling immune-mediated tissue damage versus wound healing and tissue repair response (Gu et al.,2019). Secondary hemophagocytic lymphohistiocytosis (macrophage activation syndrome), a hyperinflammatory syndrome characterized by the release of cytokines, cytopenia, and multi-organ failure, may develop in addition to high levels of cytokines (Tseng et al.,2005).

Although this response may occur across different clinical scenarios, like the syndrome of cytokine release noted among individuals participating in medical care (Frey and Porter, 2019), HLH tied to carcinomas, as well as autoimmune disease (Karakike and Giamarellos-Bourboulis, 2019), it is also pertinent to highlight its relevance with regard to The term systemic The inflammation Responding Syndrome (SIRS) along with ARDS with regards to diseases that are infectious, they are all participating in the expression of the mentioned immune system reaction (Gu et al.,2019), However, in the case of COVID-19, there is a notable occurrence of a storm of cytokines syndrome that features rapid progression within a few days following the initiation of the pathological condition, which leads to raised rate of inpatient complications and deaths (Zhang et al., 2020a).

This shows that acute respiratory distress syndrome results from the occurrence of a cytokine storm through the release by effector immune cells of large amounts of pro-inflammatory cytokines (IFNγ, IFNα, IL-1β, IL-6, IL-18, IL-33, IL-12, TNFα, TGFβ) and chemokines (CXCL10, CXCL8, CXCL3, CCL2, CCL9, CCL5) that lead the immune system to begin attacking the body and cause major damage and failure of many organs and may lead to death (Huang et al., 2020b).

Serious COVID-19-related deaths are closely associated with cytokine release syndrome, and the scientific reason because that all cells and tissues in the body are affected by this excessive cellular immune response (Montazersaheb et al., 2020).

The cytokine storm inflammatory is accompanied by immunopathological alterations in the pulmonary system, locally the excessive production of inflammatory mediators is the decisive factor that induces this pathological change and clinical manifestation. The initiation and developmentally of acute respiratory distress syndrome through viral infection is strongly linked with the occurrence of cytokine storm. Patients diagnosed with acute respiratory of the distress syndrome exhibit notable elevation the quantity of inflammatory mediators within their serum. Furthermore, there exists a positive association between the extent of this elevation and the mortality rate observed in these patients (Douda et al., 2011; Parsons et al., 2005).

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