# Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?
## 6 Corticosteroids  
The infection with SARS-CoV-1 and MERS is associated with an unregulated inflammatory response which could ultimately severely affect the respiratory system [25; 85]. Since patients with severe COVID-19 develop inflammatory-induced lung injuries, it seems that corticosteroids, including dexamethasone hydrocortisone, methylprednisolone, prednisone, and prednisolone are a good treatment option in this group [86]. Corticosteroids can be administered to decrease lung inflammatory responses which in many patients evolve into acute lung injury and acute respiratory distress syndrome (ARDS) [10]. According to the results of previous studies, corticosteroid treatment seems not to increase 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval (Cl), 0.52-1.07; \(p\) = 0.12), however, it delays MERS coronavirus RNA clearance in the respiratory and blood tracts (adjusted hazard ratio (aHR) 0.35; 95% CI, 0.17-0.72; \(p\) = 0.005) [87]. The data obtained from combined two meta-analyses based on pooled data from 8 randomized trials (including 7184 participants) of the systemic use of corticosteroids for COVID-19 demonstrated that such treatment is plausible to decrease 28-day mortality in patients with critical COVID-19 (relative risk [RR] 0.80, 95% CI 0.70-0.91) and severe disease (RR 0.80, 95% CI 0.70-0.92) [88]. However, such therapy was found to possibly increase the risk of mortality when administered to patients with non-severe COVID-19 (RR 1.22, 95% CI 0.93-1.61). Moreover, systemic corticosteroid treatment may diminish the need for invasive mechanical ventilation (RR 0.74, 95% CI 0.59-0.93). Based on these results, the WHO issued recommendations, according to which systemic corticosteroid therapy (6 mg/day of dexamethasone orally or intravenously or 50 mg/day of hydrocortisone intravenously every 8 h) should be used for 7 to 10 days in patients with severe and critical COVID-19 (with strong evidence). Corticosterol therapy should not be used in patients with non-severe COVID-19 [88]. Currently, the role of corticosteroids in the therapy of COVID-19-infected patients is primarily limited to those with ARDS [40]. Both low (25 mg/day) and moderate (140 mg/day) doses of corticosteroids were found to decrease mortality in patients with acquired pneumonia [89]. Unfortunately, the risk of excessive persistence of viral load, secondary infections as well as long-term complications while using high-dose corticosteroids cannot be excluded [10]. The response to corticosteroids as well as associated toxicities may be associated with the presence of some alleles variants in genes, including those involved in the receptor binding (e.g., _CRHR1_, _NR3C1_), metabolizing enzymes (e.g., _CYP3A4_, _CYP3A5_, _CYP3A7_, _GSTT1_), chaperone/cochaperone protein (e.g., _ST13_, _STIP1_, _FKBP5_) as well as transporters (e.g., _MDR1_, _ABCB1_) [90]. The metabolic and mechanistic pathways of steroids are complex, there is no sufficient evidence supporting the use of any of them to adjust the treatment of patients with COVID-19. The only variants associated with corticosteroids in PharmGKB had a level of evidence higher than \"low\" (level 3), however, they were evaluated in the case of combination therapy (e.g., with chemotherapy) or inhaled corticosteroids. Therefore, currently, no pharmacogenetic guideline has been published on any corticosteroid and no pharmacogenetic recommendations have been made [25]. Dexamethasone is one of the glucocorticoids used to suppress cytokine release and hinder lung infiltration by neutrophils and other leukocytes [2]. This drug is metabolized by hepatic CYP3A4 into 6-hydroxydexamethasone and other metabolites [91]. It is also a substrate of P-gp (encoded by the _ABCB1_ gene) which appears to contribute to steroid resistance [92].