**Author details**

*Genetic Variation*

**11. Conclusion**

personalize the treatment procedures.

The authors declare no conflict of interest.

**Conflict of interest**

**10. Personalized medicine guided by host genetic of COVID-19**

SARS-CoV-2 inhibition can be done by spike protein and ACE2 differential glycosylation [126]. Several polymorphisms, such as p.Pro389His, p.Met383Thr and p.Asp427Tyr slightly inhibited by hydroxychloroquine. This can be clarifying why hydroxychloroquine treatment was not significantly in a different hospital than others [127]. However, more pharmacogenomics experiments between the genetic data and drug response from COVID-19 patients are extremely needed. The viral entry to the host cell by binding to the cell membrane through S protein can be blocked by TMPRSS2 [88]. The SARS-CoV-2 pathogenesis and infection depend on the TMPRSS2 presence, in a high pH environment [128, 129]. The inhibitor of endosomal acidification such as hydroxychloroquine and CatB/L inhibitors might work only in absence of TMPRSS2- in SARS-CoV-2 infected and may not work or has no or less effective in patients with TMPRSS2 wild-type [128]. So far, the populations with missense polymorphisms and stop-gained of TMPRSS2 polymorphisms may be good sensitive to treatment with hydroxychloroquine. Furthermore, the patients who carry TMPRSS2 and ACE2 wildtype, a mix of hydroxychloroquine or chloroquine with camostat may have the best clinical advantage. The ACE2 can be cleaved by TMPRSS2 at Arginine 697 to 716 [130], which improves viral entry. Thus, patients with, p.Arg710Cys p.Arg708Trp, p.Arg716Cys and p.Arg710His polymorphisms in ACE2 might have fewer symptoms of COVID-19 disease as the cleavage site of ACE2 gene loses by these polymorphisms (**Figure 3**) [113].

The pandemic COVID-19 by SARS-CoV-2 coronavirus is multifactorial in which human inheritances might play a pivotal role together with the co-morbidity diseases and other risk factors. The disease clinical course has been depending on the link between genetic variants, such as the CYP2D6 enzyme system, HO-1 (anti-inflammatory gene), and ACE-2 enzyme. Beside ACE2 polymorphisms, there is TMPRSS2 gene variance that possibly changes the pathogenicity of the virus by changing the interaction between ACE2 and SARS-CoV-2 virus. A good characterization of functional polymorphisms and the host genetics can assist in identifying the pathophysiology of the disease pathway to stratify the risk evaluation and to

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Mahmood A. Al-Azzawi1 \* and Moustafa A. Sakr2

1 College of Dentistry, Al-Ayen University, An-Nasiriyah, Iraq

2 Genetic Engineering Institute, University of Sadat City, Sadat City, Egypt

\*Address all correspondence to: mmahmood41@yahoo.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
