The pathogenesis and treatment of the `Cytokine Storm' in COVID-19

Abstract

Cytokine storm is a general term applied to maladaptive cytokine release in response to infection and other stimuli. The pathogenesis is complex but includes loss of regulatory control of proinflammatory cytokine production, both at local and systemic levels. The disease progresses rapidly, and the mortality is high. Some evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, severe deterioration in some patients has been closely associated with dysregulated and excessive cytokine release. This article reviews what we know of the mechanism and treatment strategies of the COVID-19 virusinduced inflammatory storm in an attempt to provide some background to inform future guidance for clinical treatment.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19

“…Central to COVID-19 disease progression is the development of cytokine storm, which is thought to be sustained and amplified by evolving parallel processes: (1) the activation of macrophages and other antigen presenting cells, alerting lymphocytes to the presence of the virus, (2) viral RNA replication within host cells, activating synthesis of proinflammatory factors, and (3) viral invasion of lymphocytes, eliciting lymphocyte apoptosis and facilitating ongoing immune evasion [10,11]. The complex pathophysiology suggests that severe COVID-19 is more amenable to treatment with a pleiotropic agent rather than a single target agent.…”

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

“…These proteins are potent activators of the innate immune system, and are able to induce the monocyte-macrophage system and the activation of antigen-presenting cells [15,35]. The evidence shows that, during the COVID-19 epidemic, the severe deterioration of some patients has been closely related to a dysregulated inflammatory process referred to as "the cytokine storm" [36,37].…”

Unravelling the debate on heme effects in COVID-19 infections

“…Second, systemic hyperinflammation follows severe COVID-19 infection. This is manifested by an increase in the abundance of numerous cytokines (e.g., IL-2, IL-7, IL-6, TNFα) (Ye et al, 2020), which is indicative of cytokine release syndrome (Huang et al, 2020) and leads to elevated serum biomarkers in patients (e.g., CRP, lactate dehydrogenase (LDH), D-dimer, ferritin) Young et al, 2020;Zhang et al, 2020c;Zhou et al, 2020a). Several of these indications, however, were also reported for labile heme occurring in patients with hemolytic disorders (Litalien et al, 1999;Barcellini and Fattizzo, 2015).…”

“…In the beginning of 2020, the coronavirus disease 19 has been declared a pandemic of international concern and an unprecedented challenge for the country-specific health care systems (Cucinotta and Vanelli, 2020). COVID-19 is caused by infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is accompanied by pneumonia, acute respiratory distress syndrome (ARDS) associated with a cytokine storm, and death in the most severe cases (Ye et al, 2020;Zhou et al, 2020a). By taking a closer look into the molecular mechanisms of the infection and disease development, it is important to note that patients with severe COVID-19 often had a history of hypertension, yet also chronic kidney disease, cardiovascular disease or diabetes mellitus compared to those with milder disease progression (Ji et al, 2020;Zhou et al, 2020a).…”