Figure 1.

Cytokines and chemokines expression induced by SARS-CoV-2 in patients with COVID-19. (A) Epithelial cells have been shown to express TNF-α, IL-1, IL-6, and other chemokines (e.g., IL-8, CCL2, CCL7, CXCL10, G-CSF, and GM-CSF) as well as initiate immune responses following infection. (B) Innate immune cells, including dendritic cells, macrophages, circulating monocytes, neutrophils, and NK cells, are activated by SARS-CoV-2 infection to secrete various cytokines and chemokines to enhance both innate and adaptive immune cells. (C) Adaptive immune cells consisting of functional CD4⁺ T cells, Th1 cells, Th2 cells, Th17 cells, CD8⁺ T cells, and γδT cells defend against SARS-CoV-2 infection. The cytokines and chemokines expressed by adaptive immune cells interact in a positive feedback loop to strengthen innate immune responses. The cellular origin of each cytokine and its regulatory roles are shown in figure and Table 1. The persistent escalation of these responses leads to uncontrolled cytokine and chemokine expression, resulting in a life-threatening systemic inflammatory response syndrome, also known as “cytokine storm”. (D) Selected cytokine/chemokine modulation drugs that have been applied in COVID-19 clinical trials are shown in the upper right of the figure. They include neutralized antibodies (siltuximab, secukinumab, certolizumab); receptor antagonists (anakinra, sarilumab, tocilizumab), human recombinant proteins (IFN-β-1α, IFN-α-1β, IFN-α-2β); small-molecule drugs (baricitinib, remdesivir, molnupiravir, etanercept); and cell therapy (NKG2D-ACE2 CAR-NK cells). The drugs have been applied to COVID-19 patients to boost their immune systems and inhibit viral replication or cytokine storms. Figure created with BiorRender.com.