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.