A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization

Abstract

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.

Keywords: BCG; COVID-19(SARS Cov2); Co-morbidity; Coronavirus; Cytokine; Growth factors.

Graphical abstract

Fig. 1

Venn diagram showing peripheral cytokine profile of SARS CoV, MERS CoV and SARS CoV2 infection. IL-6, IFN-γ and IP-10 showed significantly higher levels in all three highly pathogenic hCoV infections. IL-8, MIG, IL-1, MCP-1 and IL-2 levels were altered in both SARS CoV and SARS CoV2 infected patients. TNF-α and IL-10 levels were increased in SARS CoV2 and MERS. Cytokines and chemokines like IL-1RA, IL-7, IL-9, IL-2R, GCSF, GMCSF, PDGF, CXCL16, MIP2- α, MCP-2, VEGF, bFGF, MIP1-α and MIP1-β cytokines were uniquely elevated in SARS CoV2 infection.

Fig. 2

Schematic diagram representing higher pro-inflammatory cytokines and chemokines in COVID-19 patients with underlying risk factors, with hyper-cytokinemia associated inflammation culminating in lethal complications in SARS-CoV2 infection.

Fig. 3

Antiviral immunity provided by BCG vaccine through trained immunity involves the discharge of IL-1β, TNF-α and IL-6 from epigenetically modified monocytes which confer early protection against SARS-Cov2.