The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options

Abstract

COVID-19, caused by SARS-CoV-2, emerged as the deadliest outbreak that has now become a serious health issue to mankind. Activation of inflammatory signaling pathways and cytokine storm are crucial factors that lead to acute respiratory distress syndrome (ARDS) in COVID-19 patients. Excessive secretion of pro-inflammatory cytokines and chemokines leads to the dysregulation of the innate immune system. The cytokine storm attracts many inflammatory cells that infiltrate into the lung tissues and ultimately cause immune damage. In addition to the dysregulation of the immune system, dysfunction of the renin-angiotensin system (RAS) due to the downregulation of ACE2 is also associated with the mortality of COVID-19 patients. Both the mechanisms are directly or indirectly associated with cytokine storm that promotes vascular hyperpermeability, vascular edema leading to hypercoagulation and hence multiorgan damage. As of now, there is no specific treatment available for COVID-19, but scientists have purposed several treatment options including cytokine inhibitors, JAK inhibitors, immunomodulators, plasma therapy, etc. In this article, we have provided the detailed mechanism of occurrence of SARS-CoV-2 induced inflammatory storm and its connection with the pre-existing inflammatory conditions. Possible treatment options to cope up with the severe clinical manifestations of COVID-19 are also discussed.

Keywords: ACE2; Cytokine storm; IFN- γ; IL-6; SARS-CoV-2; TNF-α; Vascular edema.

Graphical abstract

Fig. 1

Three stages of increased COVID-19 severity due to the activation of inflammatory pathways.

Fig. 2

Inflammatory signaling cascade activated in COVID-19.

Fig. 3

Role of cytokine storm in COVID-19.

Fig. 4

An interplay of cytokine storm, coagulopathy and pulmonary complications in COVID-19.

Fig. 5

SARS-CoV-2 infection and microbiota dysbiosis.