Targeting Cytokine Storm to Manage Patients with COVID-19: A Mini-Review

Abstract

Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNFα and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients. In this mini-review, we addressed the inflammatory pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship with the host cytokine storm. Furthermore, the proposed therapeutic options to reverse hyper-inflammation in infected patients were mentioned.

Keywords: COVID-19; Cytokine storm; IL-1β; IL-6; SARS-CoV-2; TNFα.

Figure 1

A proposed pathway for inducing cytokine storm following SARS-Cov-2 infection. SARS CoV-2 virus uses the angiotensin-converting enzyme 2 (ACE2) as the receptor for entering the cells. After entering to type II alveolar epithelial cells of the lungs, SARS CoV-2 triggers life-threatening cytokine release in the host, which can result in excessive levels of pro-inflammatory cytokines production including IL-6, TNF-α and IL-1β. Type II AEC, type II alveolar epithelial cells; RBC, red blood cells; IL, interleukin; TNF α, tumor necrosis factor α; IFN-γ, interferon-gamma; GCSF, granulocyte-colony stimulating factor; IP-10, interferon γ-induced protein; MCP1, monocyte chemo-attractant protein 1; MIP, macrophage inflammatory proteins; Th, T helper.