# Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?
## 10 Baricitinib  
Recently, WHO has recommended two new medications for the treatment of COVID-19 [147]. One of them is baricitinib, an inhibitor of Janus kinase (JAK). Baricitinib received emergency use authorization from the US Food and Drug Administration for hospitalized patients with COVID-19 who required oxygen supplementation [148]. It is recommended for the therapy of patients with severe or critical COVID-19, in combination with corticosteroids, especially dexamethasone. However, the use of these two immunosuppressive drugs may enhance the risk of either opportunistic infections or the recurrence of latent infections [8]. Baricitinib's mechanism of action involves the inhibition of immune system overstimulation. The treatment of hospitalized COVID-19 patients requires enhanced viral clearance and the limitation of the inflammatory response [149]. Baricitinib was demonstrated to hinder the signaling of the following cytokines: IL-2, IL-6, IL-10, IFN-\(\gamma\), and G-CSF. The anti-inflammatory and anti-cytokine properties of baricitinib make it a promising drug that can be used in the treatment of patients with COVID-19 [150]. This drug also targets host proteins, including Numb-associated kinases (AAK1, BIKE, and GAK) which are responsible for SARS-CoV-2 viral propagation [149]. Before the pandemic, baricitinib was used to treat patients with rheumatoid arthritis. COV-BARRIER, a placebo-controlled clinical trial enrolling hospitalized patients with COVID-19 and increased level of at least one inflammatory biomarker demonstrated that the administration of baricitinib 4 mg \begin{table}
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**Drug** & **Mechanism of Action** & **Pharmacogenomic Issues** & **Effectiveness of Treatment** \\ \hline \hline \multirow{8}{*}{} & \multirow{8}{*}{} & \(CYP2C9\textasci{1}2\), and \(CYP2C9\textasci{1}3\) variants—diminished function—may affect clinical benefits and cause drug toxicity as a result of drug \\  & & \(accumulation25,122]\). Functional polymorphisms within the \(ABCB1\) gene could help to predict the response to losartan [123], rs1045642, rs2032582 and rs1128503—may alter drug pharmacokinetics [124]. & No association between the use of ACE inhibitors or ARBs and SARS-CoV-2 infection in the population of COVID-19 patients or patients with severe or fatal disease [143]. \\ \multirow{8}{*}{} & \multirow{8}{*}{} & \(ACE\) rs1799752—variability in the effectiveness of captorpil, enalapril, and isinporril [125,126]. & BRACE CORONA trial—no clinical benefit of cessation of ACE inhibitors or ARBs in patients hospitalized with COVID-19 [144]. \\ \multirow{8}{*}{} & \multirow{8}{*}{} & \(ACE\) del/del diplotype—worse clinical outcome. & Reduction in the odds of hospital admission in diabetic patients receiving RAAS inhibitors [135]. \\ \multirow{8}{*}{} & \multirow{8}{*}{} & \(\text{R}\) Long-term therapy with RAAS inhibitors—lower odds of admission to semi-intensive or intensive care compared to patients not treated with RAAS inhibitors [145]. \\  & & \(ACE1\) on patients with comorbidities—higher risk of hospitalization due to COVID-19 and mortality. & Plausible mortality reduction in patients using ACE inhibitors/ARBs [146]. \\ \multirow{8}{*}{} & \multirow{8}{*}{} & \(\text{SNPs rs2106809}\) and \\  & & \(\text{rs2285666--higher risk of hospitalization and severe course of the disease.}\) & \\ \multirow{8}{*}{} & \(\text{Alternate allele (T or A) of}\) & \\  & & \(\text{rs2285666--lower infection}\) & \\ \multirow{8}{*}{} & \(\text{susceptibility and case-fatality}\) & \\ \hline \hline ARBs— Angiotensin receptor blockers; G6 PD—glucose-6 phosphate dehydrogenase; HCQ—hydroxychloroquine; MHC—major histocompatibility complex. & & \\ \end{tabular}
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Table 1: _Cont._orally had no significant effect on the occurrence of the primary endpoint (progression to high-flow oxygen), noninvasive ventilation, mechanical ventilation, or death by day 28 compared to placebo (OR 0.85; 95% CI, 0.67-1.08; \(p=0.18\)) [150].