COVID-19 infection: an overview on cytokine storm and related interventions

Abstract

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. This virus affects the respiratory tract and usually leads to pneumonia in most patients and acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is one of the leading causes of death in patients with COVID-19 and is mainly triggered by elevated levels of pro-inflammatory cytokines, referred to as cytokine storm. Interleukins, such as interleukin-6 (1L-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. The eradication of COVID-19 is currently practically impossible, and there is no specific treatment for critically ill patients with COVID-19; however, suppressing the inflammatory response may be a possible strategy. In light of this, we review the efficacy of specific inhibitors of IL6, IL1, IL-17, and TNF-α for treating COVID-19-related infections to manage COVID-19 and improve the survival rate for patients suffering from severe conditions.

Keywords: ARDS; COVID-19; CRS; IL-17; IL1; IL6; TNF-α.

Fig. 1

A panoramic review of IL-6, IL-1, IL-17, and related interventions in COVID-19-induced CRS. A The entry of SARS‐CoV‐2 into the ACE2‐expressing cells. B The modes of IL-6 signaling are depicted. IL-6 binds to the soluble or membrane-bound receptor, forming a complex with ubiquitously expressed gp130 protein. The intracellular domain of gp130 activates JAK/STAT signal transduction. The soluble form of IL-6R is mediated by the cleavage of ADAM17 enzyme. Antagonists of IL-6 (tocilizumab, sarilumab, and siltuximab) antagonize ligand-receptor engagement; thereby inhibiting IL-6 mediated signaling. sgp130Fc is an exclusive inhibitor of IL-6 trans-signaling. C Anakinra and Canakinumab antagonize the IL-1 mediated inflammation via binding to corresponding receptors. D IL-17 is a member of pro-inflammatory cytokines, having a critical role in the recruitment of monocytes and neutrophils to the inflamed sites. IL-17 has mediated its activity via binding to corresponding receptors (IL-17R), activating inflammation-related signaling. SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; ACE2: angiotensin-converting enzyme 2; sIL-6R: the soluble form of the receptor; JAK/STAT: Janus kinase/signal transducer and activator of transcription