Besides structural parts of the virus, various steps associated with the innate and the adaptive immune responses have been proposed as the most important targets of interest. For instance, the significant rise in the level of chemokines and cytokines, including IL-1β, IFN-γ, IP-10, and MCP-1, which is called the cytokine storm, can be inhibited by antibodies [69]. The preliminary studies of critically ill COVID-19 patients have shown that IL-6 may cause severe inflammatory responses that lead to acute respiratory distress syndrome [70]. Herein, tocilizumab, an IL-6 inhibitor monoclonal antibody, has gained significant attention. In a 21-patient clinical study recruited in China, tocilizumab resulted in the reduction of oxygen need in 75% of patients, lung lesion opacity absorption in 90.5% of patients, and correction of lymphocyte and C-reactive protein levels [70]. The significance of tocilizumab can be better explained since a noticeable number of 46 clinical trials regarding its use against SARS-CoV-2 related pneumonia and respiratory tract infections were recorded in NIH until May 27, 2020. An increase in the level of some of these pro-inflammatory cytokines such as granulocyte–macrophage colony-stimulating factor (GM-CSF) results in a positive feedback in the number of other inflammatory mediators, including IL6, IL-23, and TNF. GM-CSF along with IL6 and IL23 also induce Th1/Th17 differentiation and the polarization of macrophages to M1 phenotypes, which in turn boost the inflammatory responses [71]. Th17 immune response also can aggravate the cytokine storm by raising the level of IL17, GM-CSF, IL21, and IL22 [72]. High levels of GM-CSF and Th17 cells were observed in the plasma of severe- to critically ill COVID-19 patients [73], [74]. Herein, harnessing the upregulation of GM-CSF can prevent a cascade of inflammatory responses, which result in acute respiratory syndrome. Since monoclonal antibodies targeting one inflammatory mediator, may fail to control the whole cytokine storm and prevent the lung injury induced by acute respiratory distress syndrome, a newer approach to prevent lung injury was proposed. It was shown that physical stress such as excessive mechanical stress caused by ventilators upregulates the expression of a gene, called nicotinamide phosphoribosyltransferase (NAMPT). As the bioavailability of NAMPT increases, Toll-like receptor 4 (TLR4), which is responsible for lung inflammation, gets activated [75], [76]. Herein, neutralization of circulating NAMPT by monoclonal antibodies can be another viable approach in preventing the lung injury caused by SARS-CoV-2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441891/