Introduction:
The coronavirus SARS-CoV-2 has infected more than 250 million people and caused death to over than 5 million, with a worldwide mortality rate of 2%. Many patients who die from COVID-19 suffer from hyper-inflammation caused by cytokine storm syndrome (CSS) and associated acute respiratory distress syndrome [1]. The antiviral Remdesivir was shown to reduce the length of hospital stay for COVID-19 patients, but anti-inflammatory agents have improved survival in these patients [2]. The greatest survival rate has been found with glucocorticoids, which play as immunosuppressive agents, when given to patients with an oxygen requirement. However, patients treated with glucocorticoids may fare worse than those who receive standard care in the absence of an oxygen requirement or systemic inflammation. The selection of patients and timing of glucocorticoids administration is critical for survival benefit. Optimal treatment of targeted anti-cytokine therapy to prevent CSS is suggested earlier without increasing viral replication [3].
Cytokine storm syndrome (CSS) is characterized by secretion of large amounts of cytokines including IL-1α, IL-1β, IL-6, IL-18 and TNF-α, continuous activation of lymphocytes and macrophages causing immune dysregulation, and finally, overwhelming systemic inflammation and multi-organ failure (MOF) with high mortality [4].
The term CSS was first used after allogeneic stem cell transplant to describe the hypercytokinemia (increased blood cytokines) in graft. Many viral, bacterial and parasitic infections can cause CSS such as Mycobacterium tuberculosis and Epstein-Barr virus (EBV), which cause pathological immune activation characterized by elevated cytokines such as interferon-γ (IFN-γ) in patients with immune defects [5].
Levels of inflammatory cytokines especially IL-6, IL-8, MCP-1 and TNFα are significantly increased in COVID-19 plasma. Plasma levels of IL-8 are strongly associated with circulating vWF levels. Local and systemic circulating inflammatory markers concur with several markers revealing endothelial activation and damage in COVID-19 patients.