2020
DOI: 10.1016/j.cyto.2020.155151
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Abstract: Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine … Show more

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Cited by 392 publications
(440 citation statements)
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“…The positive response showed by COVID-19 patients towards intravenous steroid therapy and immunotherapy (IVIg and plasmapheresis) commonly used in in the autoimmune conditions such as, myasthenia gravis and GBS proved that there was an immune process in the occurrence of encephalitis. 53 Based on the theories from the previous studies 54,55,56 the pathomechanism of immune-mediated cerebral damage in COVID-19-associated encephalitis were illustrated (Fig. 2).…”
Section: Systemic Review Analysismentioning
confidence: 99%
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“…The positive response showed by COVID-19 patients towards intravenous steroid therapy and immunotherapy (IVIg and plasmapheresis) commonly used in in the autoimmune conditions such as, myasthenia gravis and GBS proved that there was an immune process in the occurrence of encephalitis. 53 Based on the theories from the previous studies 54,55,56 the pathomechanism of immune-mediated cerebral damage in COVID-19-associated encephalitis were illustrated (Fig. 2).…”
Section: Systemic Review Analysismentioning
confidence: 99%
“…The binding of SARS-CoV-2 to ACE2 receptor via spike protein, caused ACE 2 downregulation 50,54 , followed by an increase in ACE / Angiotensin II / AT1R axis, and a decrease in ACE2 / Mas receptor (MaSR) axis. 54 Consequently, these resulted to the activation of the nuclear factor kappa B (NF-kappa B) pathway, Mitogen-Activated Protein Kinase (MAPK) pathway, upregulation of tumor growth factor beta (TGF-beta) accompanied by downregulation of anti-in ammatory cytokine IL-10. 54.55 Therefore, the increased proin ammatory pathways rised the levels of monocyte chemotactic protein 1 (MCP-1) ), vascular cell adhesion molecule 1 (VCAM-1), selectin-E, and interlekukin 6 (IL-6).…”
Section: Systemic Review Analysismentioning
confidence: 99%
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“…ACE2 acts as mediator of coronavirus entry into the cells, but also contributes to diffuse alveolar damage through imbalances in the renin-angiotensin system. These immunologic reactions in severe COVID-19 may characterize the cytokine storm phenomenon: a massive release of macrophage migration inhibitory factor (MIF), tumour necrosis factor (TNF)-α, and interleukin (IL)-1, IL-2R, IL-6, IL-8, and IL-10 from host cells and immune cells [5,6]. These in ammatory cells and factors will lead to the typical ARDS (Acute respiratory distress syndrome) pathology with acute diffuse alveolar damage, pulmonary oedema, and formation of hyaline membranes [7].…”
Section: Introductionmentioning
confidence: 99%
“…Although the factors that condition the progression of the disease in severe cases are not fully understood, evidence seems to show that the symptoms in patients with moderate to severe disease due to SARS-CoV-2 are related not only to viral proliferation, but also to two factors related to its pathogenesis: i) an exacerbated inflammatory response associated with increased concentrations of proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukins (IL), including IL-1 and IL-6 [8][9][10][11], and ii) abnormalities in coagulation and thrombosis, similar to a combination of mild disseminated intravascular coagulopathy and a localized pulmonary thrombotic microangiopathy, which could have a substantial impact on organ dysfunction in the more severely affected patients [12].…”
Section: Introductionmentioning
confidence: 99%