AUTHOR=Fricke-Galindo Ingrid , Falfán-Valencia Ramcés 

TITLE=Genetics Insight for COVID-19 Susceptibility and Severity: A Review

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.622176

DOI=10.3389/fimmu.2021.622176

ISSN=1664-3224

ABSTRACT=<p>Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to a severe clinical course. The host genetic background influence on the susceptibility and outcome of multiples infectious diseases has been previously reported. Herein, we aimed to describe relevant identified genetic variants and those potentially related to the inter-individual variability of COVID-19 susceptibility and/or severity considering the physiopathological pathway of the disease The <italic>HLA-A*25:01</italic>, -<italic>B*15:27</italic>, <italic>-B*46:01</italic>, <italic>-C*01:02</italic>, and <italic>-C*07:29</italic> alleles have been associated with COVID-19 susceptibility; while <italic>HLA-A*02:02</italic>, <italic>-B*15:03</italic>, and <italic>-C*12:03</italic> have been identified as low-risk alleles. Variants in cytokine genes such as <italic>IL1B</italic>, <italic>IL1R1</italic>, <italic>IL1RN</italic>, <italic>IL6</italic>, <italic>IL17A</italic>, <italic>FCGR2A</italic>, and <italic>TNF</italic> could be related to disease susceptibility and cytokine storm, and/or COVID-19 complications (e.g., venous thrombosis). Several variants in <italic>ACE2</italic> and <italic>TMPRSS2</italic> affecting the expression of the receptors related to COVID-19 have been associated with the disease susceptibility and risk factors. Finally, two GWAS have identified the <italic>loci</italic> 3p21.31 (<italic>LZTFL1</italic>, <italic>SLC6A20</italic>, <italic>CCR9</italic>, <italic>FYCO1</italic>, <italic>CXCR6</italic>, and <italic>XCR1</italic>) and 9q34.2 (<italic>ABO</italic>) with COVID-19 severity. Heterogeneous results in the association of genetic variants with COVID-19 susceptibility and severity were observed. The mechanism of identified risk-genes and studies in different populations are still warranted.</p>