# Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?
## 8 Tocilizumab  
Since severe COVID-19 is associated with a cytokine-release syndrome with increased interleukin-6 (IL-6), it seems reasonable to use monoclonal antibodies directed against key inflammatory cytokines as the treatment option [40]. Interleukin-6 (IL-6) is a key trigger of this dysregulated inflammation [106]. It appears that monoclonal antibodies against IL-6 can reduce this process and ameliorate clinical outcomes [10]. One of the IL-6 receptor inhibitors--tocilizumab--is commonly used in the treatment of rheumatoid arthritis (RA) and cytokine-release syndrome triggered by chimeric antigen receptor-T cell therapy [40]. Due to its potential, it is currently under investigation for COVID-19. Typical doses of tocilizumab are 400 mg or 8 mg/kg in one or two doses, with the second dose given 8-12 h after the first one if the response is inadequate [10; 107]. Some studies found that it is effective in severe COVID-19 cases [10; 107]. Such therapy was suggested to decrease the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia [108]. Several genetic variations have been demonstrated to modulate the efficacy of tocilizumab in RA, for example in _FCGR3A_, _IL6R_, _CD69_, and _GALNT18_ genes, therefore, the same can apply to the treatment of COVID-19 patients [109; 110; 111]. However, no wide-scale pharmacogenomic studies of tocilizumab have been conducted in patients with any cytokine-release syndrome resembling the physiology in COVID-19. Some studies assessed the relationship between genetic polymorphisms within the _IL6R_ gene and tocilizumab response [25]. It was found that carriers of IL6R rs4329505 CC and CT genotypes displayed worse response to tocilizumab compared with RA patients with TT genotype [112]. Furthermore, rs12083537 AA genotype correlated with reduced response to tocilizumab and increased risk for asthma when compared with the AG genotype. In turn, [PERSON] et al. [110] found that the rs11265618 CC genotype was associated with enhanced response to to tocilizumab in comparison to CT and TT genotypes. The presence of functional SNPs within the _IL6R_ gene could exert an impact on the intracellular signaling pathway of the IL-6 receptor bound to tocilizumab [110]. Moreover, polymorphisms within the _FCGR3A_ gene may modify the efficiency of treatment due to changes in systemic exposure. Patients with the _FCGR3A_ rs396991 AA genotype may have an increased response to tocilizumab as compared with patients carrying AC or CC genotypes [109]. The study of patients with RA treated with tocilizumab demonstrated higher response at 12 months in carriers of _FCGR3A_ rs396991 TT genotype (vs. GT; OR: 5.1; 95% CI: 1.2-21.3; \(p=0.03\)) [109]. According to the authors, this variant may alter the affinity of the Fc fragment of IgG receptor to tocilizumab and change its systemic clearance. Greater response to tocilizumab was also reported in patients with the _CD69_ rs11052877 AA compared to patients with the AG and GG genotypes, as well as in carriers of _GALNT18_ rs4910008 CC individuals compared with patients with the CT and TT genotypes [111]. Variants in _CD69_ and _GALNT18_ genes were suggested to affect the downstream signaling pathways of the immune system in RA patients, therefore, their effects may not be visible in non-RA patients [111]. Currently, there is no strong evidence indicating that the analysis of pharmacogenomic biomarkers would be helpful in predicting response to tocilizumab therapy in patients with COVID-19.