Table 3.

Gene Validation by related covid-19 literature.

Autoimmune, metabolic, and neurological diseases
Verified HLA-DRB1 HLA-DQA1 CTLA4 VEGFA ITGB3 ITGA2 IRS1 MT-ND3 NOS3 ABCB2	HLA is associated with risk for severe COVID-19. CTLA4 expression levels were correlated with viral levels. VEGFA increases endothelial dysfunction and correlates with COVID-19 disease severity, stimulates sensory receptors in central and peripheral nervous systems, cooperates with sars-cov2 spike protein to induce analgesia. CTLA4: HLA: VEGFA are highly expressed and associated with progression, immune regulation, and symptoms in COVID patients. ITGB2/3 SARS-CoV-2 infection revealed changes in genes related to coagulation (ITGB3). IRS1 Sars-cov-2 viral infection activates stress response, which induce IRS-1 phosphorylation and insulin resistance. MT-MD3 mitochondrial gene downregulated in sars-cov-2. NOS3 constitutes an important endothelial protection mechanism. However, ARDS diffuse inflammatory process triggers a vasodilatation cascade in non-ventilated parts of the lungs (deregulating hypoxic vasoconstrictive mechanisms) and vasoconstriction in ventilated areas. The imbalance between vasoconstricting and vasodilating pathways leads to endothelium dysfunction. ABCB contributes to drug resistance, lysosomal accumulation of COVID-19 treatments and related to virus replications.
Unverified	NTRK1
Cardiovascular & other degenerative diseases
Verified APOC1 APOE APOC3 SLC19A1 GPX1	APOC1: APOE: APOC3 are early prognostic biomarkers for progression to severe COVID-19. A blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients showing that these regulators of lipid homeostasis increased over the course of the disease. SLC19A1. Lymphocyte Changes in Severe COVID-19: Delayed Over-Activation of STING and highly express the cGAMP importer SLC19A1. GPX1 role of selenium-dependent GPX1 in SARS-CoV-2 virulence as a molecular target.
Unverified	TOMM40, NR1I2, SORCS2, B4GALT2
Drug Metabolism
Verified G6PD CYP4F2 CYP2C9 CYP2C19 CYP3A4 CYP2D6 CYP3A5 UTG1A1 UTG1A3 UTG1A6 UTG1A7 PTGS1	G6PD deficiency facilitates human coronavirus infection due to glutathione depletion and shows a potential link between inherited G6PD deficiency and the racial inequities in mortality. G6PD was significantly induced in the lungs in COVID-19 obese patients. G6PD deficient cells infected with human coronavirus show impaired cellular responses, viral proliferation and worsening oxidative damage. G6PD deficiency is a predisposing factor of COVID-19 and deficient individuals are at high risk of severe hemolysis and or thrombosis when given anti-malarial treatment. CYP4F2: CYP2C9: CYP2C19: CYP3A4: CYP2D6: CYP3A5. Many PGx studies had evaluated the Genetic polymorphisms in members of cytochrome p450 (CYPs) that complicate COVID-19 therapy. UTG1A1: UTG1A3: UTG1A6: UTG1A7 are associated with bilirubin, a compound that occurs in the normal catabolic pathway that breaks down heme. COVID-19 patients with elevated bilirubin levels had a higher mortality. Polymorphism in the UGT1A1 gene has been observed in a patient’s case with Gilbert Syndrome attenuating COVID-19 metabolic disturbances. PTGS1 inhibition with COVID-19 treatments triggers upregulation of IL10 gene expression and represses platelet aggregation.
Unverified	ENOSF1, ABCC2, SLCO1B1, PEAR1
Disconnected genes
Verified VDR ZSCAN25 ABCB1	VDR exerts a critical role in prevention and protection of viral acute respiratory infection. VDR deficiency can aggravate respiratory syndrome by igniting a wounding response in stellate cells of the lung. VDR related genetic variants were implicated in severe COVID-19 in adults. ZSCAN25 associates with Sex Hormone-Binding Globulin (SHBG) Levels. Low SHBG were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. ABCB1 has a possible role in lysosomal accumulation of COVID-19 treatments and related to virus replications.
Unverified	BCC1, TYMS, NAT2, MTR, TYMSOS, SLCO2B1

30 genes are found in literature that are related to COVID-19 susceptibility whereas 15 genes are not yet verified, however they have been predicted as candidate genes in relation to COVID-19 disease.