An enlightening role for cytokine storm in coronavirus infection

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).

Etoricoxib may inhibit cytokine storm to treat COVID-19

“…IL-6 is considered to be the most important factor associated with cytokine storm, and the level of IL-6 in patients can be increased up to 1000 times that of normal individuals, while IL-1β and TNF-α can be increased up to 100 times that of normal individuals. Related research also supports that the level of IL-6 has a high correlation with death due to COVID-19 [3] . This evidence shows that suppressing cytokine storm may be an important way to improve the survival rate of COVID-19 patients.…”

“…Additionally, since etoricoxib does not act on COX-1, compared with that of nonselective COX inhibitors, the risk of damage to the lining of the gastric mucosa is greatly reduced, and the potential risk of damage to the regulation of platelet functions, renal hemodynamics and electrolyte balance is also reduced [7] . This finding also indicates that compared with nonselective COX inhibitors, etoricoxib is beneficial to the potential intestinal and renal symptoms of COVID-19 patients [3] . Etoricoxib has been used for the treatment of rheumatoid arthritis, psoriatic arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout.…”

Characterization of Headache in COVID-19: a Retrospective Multicenter Study

“…A so-called cytokine storm can occur in COVID-19 patients involving the massive release of inflammatory mediators including cytokines, glutamate, PGE 2 , NO, and reactive oxygen species which affect the hypothalamus triggering fever, along with activation of microglia, macrophages, astrocytes, and endothelial cells, disrupting the blood brain barrier [27]. This same release of cytokines can lead to widespread pulmonary involvement and multiorgan failure in some patients [28].…”

Human gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection

“…In severe cases of SARS-CoV-2 infection, high concentrations of innate inflammatory cytokines, including type I interferons (IFNs), tumor necrosis factor α (TNF-α), IL-6, IL-1β, and some chemokines, including CCL-2, CCL-3, CCL-5, and IP-10, are secreted by epithelial and immune cells [ 66 ]. This uncontrolled and excessive release of pro-inflammatory cytokines, i.e., cytokine storm, has been observed in patients infected with influenza virus, SARS-CoV, and MERS-CoV [ 66 , 67 ]. A cytokine storm is characterized by a strong proliferation and hyperactivation of T lymphocytes, overexpression of more than 100 pro-inflammatory genes, and massive endothelial and epithelial cell apoptosis of the lung, which results in alveolar edema, hypoxia and ARDS, and finally, death [ 66 , 68 ].…”