The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients

Abstract

Coronavirus disease 2019 (COVID-19) pandemic has affected health care systems worldwide. Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a "cytokine storm" causing inflammatory response and destruction, mainly affecting the lungs. COVID-19 activation of transcription factor, NF-kappa B (NF-κB) in various cells such as macrophages of lung, liver, kidney, central nervous system, gastrointestinal system and cardiovascular system leads to production of IL-1, IL-2, IL-6, IL-12, TNF-α, LT-α, LT-β, GM-CSF, and various chemokines. The sensitised NF-κB in elderly and in patients with metabolic syndrome makes this set of population susceptible to COVID-19 and their worse complications, including higher mortality. Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. Inhibition of NF-κB pathway has a potential therapeutic role in alleviating the severe form of COVID-19.

Keywords: COVID-19; Cytokine storm; Immunomodulation; MERS; NF-κb; SARS; Therapeutic role.

Fig. 1

Schematic diagram explaining the mechanism of action of NF-κB in COVID-19 via various pathways leading to “cytokine storm syndrome”

Fig. 2

Schematic diagram showing the mechanism of action of various drugs used in COVID-19 and how they inhibit the NF-κB pathway