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Genetic Associations with Coronavirus Susceptibility and Disease Severity

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Application of Omic Techniques to Identify New Biomarkers and Drug Targets for COVID-19

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 1412))

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global public health emergency, and the disease it causes is highly variable in its clinical presentation. Host genetic factors are increasingly recognised as a determinant of infection susceptibility and disease severity. Several initiatives and groups have been established to analyse and review host genetic epidemiology associated with COVID-19 outcomes. Here, we review the genetic loci associated with COVID-19 susceptibility and severity focusing on the common variants identified in genome-wide association studies.

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References

  1. Huang C, Wang Y, Li X, et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395. https://doi.org/10.1016/S0140-6736(20)30183-5

  2. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020) The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 5(4):536–544

    Article  Google Scholar 

  3. Zhou F, Yu T, Du R, et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395(10229):1054–1062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kwok AJ, Mentzer A, Knight JC (2020) Host genetics and infectious disease: new tools, insights and translational opportunities. Nat Rev Genet 22(3):137–153

    Article  PubMed  PubMed Central  Google Scholar 

  5. Barmania F, Pepper MS (2013) C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection. Appl Transl Genom 2:3–16

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Claireaux M, Robinot R, Kervevan J, et al (2022) Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry. Nat Commun 13(1):521. https://doi.org/10.1038/s41467-022-28130-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. The COVID-19 Host Genetics Initiative (2021) Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis. medRxiv. 2021:2021.03.10.21252820. https://doi.org/10.1101/2021.03.10.21252820

  8. Jackson CB, Farzan M, Chen B, Choe H (2022) Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23(1):3–20

    Article  CAS  PubMed  Google Scholar 

  9. Zhang S, Wang L, Cheng G (2022) The battle between host and SARS-CoV-2: Innate immunity and viral evasion strategies. Mol Ther 30(5):1869–1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Galati D, Zanotta S, Capitelli L, Bocchino M (2022) A bird’s eye view on the role of dendritic cells in SARS-CoV-2 infection: Perspectives for immune-based vaccines. Allergy 77(1):100–110

    Article  CAS  PubMed  Google Scholar 

  11. Sette A, Crotty S (2021) Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 184(4):861–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Thevarajan I, Nguyen THO, Koutsakos M, et al (2020) Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 26(4):453–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Boppana S, Qin K, Files JK, et al (2021) SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence. PLOS Pathog 17(7):e1009761. https://doi.org/10.1371/journal.ppat.1009761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shrock E, Fujimura E, Kula T, et al (2020) Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science 370(6520):eabd4250. https://doi.org/10.1126/science.abd4250

  15. Hadjadj J, Yatim N, Barnabei L, et al (2020) Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369(6504):718. https://doi.org/10.1126/science.abc6027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Masood KI, Yameen M, Ashraf J, et al (2021) Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome. Sci Rep 11(1):22958. https://doi.org/10.1038/s41598-021-02489-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Darif D, Hammi I, Kihel A, et al (2021) The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microb Pathog 53:104799. https://doi.org/10.1016/j.micpath.2021.104799

    Article  CAS  Google Scholar 

  18. Kaneko N, Kuo HH, Boucau J, et al (2020) The loss of Bcl-6 expressing T follicular helper cells and the absence of germinal centers in COVID-19. SSRN 3652322-. https://doi.org/10.2139/ssrn.3652322.

  19. Juno JA, Tan HX, Lee WS, et al (2020) Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19. Nat Med 26(9):1428–1434

    Article  CAS  PubMed  Google Scholar 

  20. Garcia-Beltran WF, Lam EC, Astudillo MG, et al (2021) COVID-19-neutralizing antibodies predict disease severity and survival. Cell 184(2):476–488.e11

    Google Scholar 

  21. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet. 2020;28(6):715–718

    Google Scholar 

  22. Kousathanas A, Pairo-Castineira E, Rawlik K, et al (2022) Whole-genome sequencing reveals host factors underlying critical COVID-19. Nature 607(7917):97–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. The GTEx Consortium atlas of genetic regulatory effects across human tissues (2020) Science 369(6509):1318–1330

    Google Scholar 

  24. Dhar P, McAuley J (2019) The Role of the Cell Surface Mucin MUC1 as a Barrier to Infection and Regulator of Inflammation. Front Cell Infect Microbiol 9:117. https://doi.org/10.3389/fcimb.2019.00117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. The Severe COVID-19 GWAS Group (2020) Genomewide Association Study of Severe Covid-19 with Respiratory Failure. NEJM. 2020;383(16):1522–1534

    Google Scholar 

  26. Zeberg H, Pääbo S (2020) The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature 587(7835):610–612

    Article  CAS  PubMed  Google Scholar 

  27. Pairo-Castineira E, Clohisey S, Klaric L, et al. Genetic mechanisms of critical illness in Covid-19. Nature. 2021; 591(7848):92–98

    Article  PubMed  Google Scholar 

  28. Roberts GHL, Park DS, Coignet MV, et al (2020) AncestryDNA COVID-19 Host Genetic Study Identifies Three Novel Loci. medRxiv 2020.10.06.20205864. https://doi.org/10.1101/2020.10.06.20205864

  29. Shelton JF, Shastri AJ, Ye C, et al (2021) Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity. Nat Genet 53(6):801–808

    Article  CAS  PubMed  Google Scholar 

  30. The COVID-19 Host Genetics Initiative (2021) Mapping the human genetic architecture of COVID-19. Nature 600(7889):472–477

    Article  Google Scholar 

  31. Roberts GHL, Partha R, Rhead B, et al (2022) Expanded COVID-19 phenotype definitions reveal distinct patterns of genetic association and protective effects. Nat Genet 54(4):374–381

    Article  CAS  PubMed  Google Scholar 

  32. Horowitz JE, Kosmicki JA, Damask A, et al (2022) Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease. Nat Genet 54(4):382–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xiao G, Wang X, Wang J, et al (2015) CXCL16/CXCR6 chemokine signaling mediates breast cancer progression by pERK1/2-dependent mechanisms. Oncotarget 6(16):14165–14178

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wein AN, McMaster SR, Takamura S, et al (2019) CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways. J Exp Med 216(12):2748–2762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Dai Y, Wang J, Jeong HH, et al (2021) Association of CXCR6 with COVID-19 severity: delineating the host genetic factors in transcriptomic regulation. Hum Genet 140(9):1313–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Downes DJ, Cross AR, Hua P, et al (2021) Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus. Nat Genet 53(11):1606–1615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Stewart CA, Gay CM, Ramkumar K, et al (2021) Lung Cancer Models Reveal Severe Acute Respiratory Syndrome Coronavirus 2-Induced Epithelial-to-Mesenchymal Transition Contributes to Coronavirus Disease 2019 Pathophysiology. J Thorac Oncol 16(11):1821–1839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yao Y, Ye F, Li K, et al (2021) Genome and epigenome editing identify CCR9 and SLC6A20 as target genes at the 3p21.31 locus associated with severe COVID-19. Signal Transduct Target Ther 6(1). https://doi.org/10.1038/s41392-021-00519-1

  39. Vuille-dit-Bille RN, Camargo SM, Emmenegger L, et al (2015) Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids 47(4):693–705

    Article  CAS  PubMed  Google Scholar 

  40. Rentzsch P, Witten D, Cooper GM, et al (2019) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47(D1):D886–D894

    Article  CAS  PubMed  Google Scholar 

  41. Dong B, Zhou Q, Zhao J, et al (2004) Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J Virol 78(17):8983–8993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Luo W, Zhang J, Liang L, et al (2018) Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication. PLoS Pathog 14(1):e1006851. https://doi.org/10.1371/journal.ppat.1006851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li S, Wang Y, Zhang Y, et al (2012) Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2. Development 139(14):2500–2509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wiehagen KR, Corbo-Rodgers E, Li S, et al (2012) Foxp4 is dispensable for T cell development, but required for robust recall responses. PLoS One 7(8):e42273. https://doi.org/10.1371/journal.pone.0042273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hao K, Bossé Y, Nickle DC, et al (2012) Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma. PLOS Genet 8(11):e1003029. https://doi.org/10.1371/journal.pgen.1003029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dai J, Lv J, Zhu M, et al (2019) Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations. Lancet Respir Med 7(10):881–891

    Article  PubMed  PubMed Central  Google Scholar 

  47. Manichaikul A, Wang XQ, Sun L, et al (2017) Genome-wide association study of subclinical interstitial lung disease in MESA. Respir Res 18(1):97. https://doi.org/10.1186/s12931-017-0581-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Contou D, Cally R, Sarfati F, et al (2021) Causes and timing of death in critically ill COVID-19 patients. Crit Care 25(1):79. https://doi.org/10.1186/s13054-021-03492-x

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ling YH, Wong CC, Li KW, et al (2014) CCHCR1 interacts with EDC4, suggesting its localization in P-bodies. Exp Cell Res 327(1):12–23

    Article  CAS  PubMed  Google Scholar 

  50. Tervaniemi MH, Katayama S, Skoog T, et al (2018) Intracellular signalling pathways and cytoskeletal functions converge on the psoriasis candidate gene CCHCR1 expressed at P-bodies and centrosomes. BMC Genomics 19(1):432. https://doi.org/10.1186/s12864-018-4810-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Farhud DD, Zarif Yeganeh M (2013) A brief history of human blood groups. Iran J Public Health 42(1):1–6

    PubMed  PubMed Central  Google Scholar 

  52. Abegaz SB (2021) Human ABO Blood Groups and Their Associations with Different Diseases. Biomed Res Int 2021:6629060. https://doi.org/10.1155/2021/6629060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wu Y, Feng Z, Li P, Yu Q (2020) Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19. Clinica Chimica Acta 509:220–223

    Article  CAS  Google Scholar 

  54. Liu D, Yang J, Feng B, et al (2021) Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19. J Infect 82(1):126–132

    Article  CAS  PubMed  Google Scholar 

  55. Gérard C, Maggipinto G, Minon JM (2020) COVID-19 and ABO blood group: another viewpoint. British Journal of Haematology 190(2):e93–e4. https://doi.org/10.1111/bjh.16884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Anisul M, Shilts J, Schwartzentruber J, et al (2021) A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance. Elife 10:e69719. https://doi.org/10.7554/eLife.69719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Boukhari R, Breiman A, Jazat J, et al (2021) ABO Blood Group Incompatibility Protects Against SARS-CoV-2 Transmission. Front Microbiol 12:799519. https://doi.org/10.3389/fmicb.2021.799519

    Article  PubMed  Google Scholar 

  58. Pairo-Castineira E, Rawlik K, Klaric L, et al (2022) GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19. medRxiv 2022.03.07.22271833. https://doi.org/10.1101/2022.03.07.22271833.

  59. Zeberg H, Pääbo S (2021) A genomic region associated with protection against severe COVID-19 is inherited from Neandertals. Proc Natl Acad Sci USA 118(9):e2026309118. https://doi.org/10.1073/pnas.2026309118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Choi UY, Kang JS, Hwang YS, Kim YJ (2015) Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases. Exp Mol Med 47(3):e144–e. https://doi.org/10.1038/emm.2014.110

  61. Huffman JE, Butler-Laporte G, Khan A, et al (2022) Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19. Nat Genet 54(2):125–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wickenhagen A, Sugrue E, Lytras S, et al (2021) A prenylated dsRNA sensor protects against severe COVID-19. Science 374(6567):eabj3624. https://doi.org/10.1126/science.abj3624

  63. Zhou S, Butler-Laporte G, Nakanishi Tet al. A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity. Nat Med. 2021;27(4):659–667

    Article  CAS  PubMed  Google Scholar 

  64. Pathak GA, Karjalainen J, Stevens C, et al (2022) A first update on mapping the human genetic architecture of COVID-19. Nature 608(7921):E1–E10. https://doi.org/10.1038/s41586-022-04826-7

    Article  CAS  Google Scholar 

  65. Hediger MA, Romero MF, Peng JB, et al (2004) The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflugers Arch 447(5):465–468

    Article  CAS  PubMed  Google Scholar 

  66. Schumann T, König J, Henke C, et al (2020) Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease. Pharmacol Rev 72(1):343. https://doi.org/10.1124/pr.118.015735.

    Article  CAS  PubMed  Google Scholar 

  67. Degenhardt F, Ellinghaus D, Juzenas S, et al (2022) Detailed stratified GWAS analysis for severe COVID-19 in four European populations. Hum Mol Genet ddac158. https://doi.org/10.1093/hmg/ddac158

  68. Stefansson H, Helgason A, Thorleifsson G, et al (2005) A common inversion under selection in Europeans. Nat Genet 37(2):129–137

    Article  CAS  PubMed  Google Scholar 

  69. Benner C, Spencer CC, Havulinna AS, et al (2016) FINEMAP: efficient variable selection using summary data from genome-wide association studies. Bioinformatics 32(10):1493–1501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Delorey TM, Ziegler CGK, Heimberg G, et al (2021) COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature 595(7865):107–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhang Y, Lu L, Furlonger C, et al. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat Immunol 1(5):392–397

    Google Scholar 

  72. Wang W, Li Q, Zhang J, et al (2010) Hemokinin-1 activates the MAPK pathway and enhances B cell proliferation and antibody production. J Immunol 184(7):3590–3597

    Article  CAS  PubMed  Google Scholar 

  73. Janelsins BM, Mathers AR, Tkacheva OA, et al (2009) Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity. Blood 113(13):3017–3026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Schneider WM, Chevillotte MD, Rice CM (2014) Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol 32:513–545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Muromoto R, Oritani K, Matsuda T (2022) Current understanding of the role of tyrosine kinase 2 signaling in immune responses. World J Biol Chem 13(1):1–14

    Article  PubMed  PubMed Central  Google Scholar 

  76. Minegishi Y, Saito M, Morio T, et al (2006) Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25(5):745–55

    Article  CAS  PubMed  Google Scholar 

  77. Kreins AY, Ciancanelli MJ, Okada S, et al (2015) Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome. J Exp Med 212(10):1641–1662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dendrou CA, Cortes A, Shipman L, et al (2016) Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med 8(363):363ra149. https://doi.org/10.1126/scitranslmed.aag1974

  79. Boisson-Dupuis S, Ramirez-Alejo N, Li Z, et al (2018) Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant. Sci Immunol 3(30):eaau8714. https://doi.org/10.1126/sciimmunol.aau8714

  80. Kerner G, Ramirez-Alejo N, Seeleuthner Y, et al (2019) Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry. Proc Natl Acad Sci USA 116(21):10430–10434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Li Z, Gakovic M, Ragimbeau J, et al (2013) Two rare disease-associated Tyk2 variants are catalytically impaired but signaling competent. J Immunol 190(5):2335–2344

    Article  CAS  PubMed  Google Scholar 

  82. Couturier N, Bucciarelli F, Nurtdinov RN, et al (2011) Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility. Brain 134(3):693–703

    Article  PubMed  Google Scholar 

  83. Callahan V, Hawks S, Crawford MA, et al (2021) The Pro-Inflammatory Chemokines CXCL9, CXCL10 and CXCL11 Are Upregulated Following SARS-CoV-2 Infection in an AKT-Dependent Manner. Viruses 13(6):1062. https://doi.org/10.3390/v13061062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Chu H, Chan JF, Wang Y, et al (2020) Comparative Replication and Immune Activation Profiles of SARS-CoV-2 and SARS-CoV in Human Lungs: An Ex Vivo Study With Implications for the Pathogenesis of COVID-19. Clin Infect Dis 71(6):1400–1409

    Article  CAS  PubMed  Google Scholar 

  85. Zhong FL, Robinson K, Teo DET, et al. Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. J Biol Chem. 2018;293(49):18864–18878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wang L, Balmat TJ, Antonia AL, et al. An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility. Genome Med. 2021;13(1):83. https://doi.org/10.1186/s13073-021-00904-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 2015;348(6235):648–660

    Article  Google Scholar 

  88. Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, et al (2021) Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6(57). https://doi.org/10.1126/sciimmunol.abg9873

    Article  Google Scholar 

  89. Kelly RJ, Rouquier S, Giorgi D, et al (1995) Sequence and expression of a candidate for the human Secretor blood group alpha(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem 270(9):4640–4649

    Article  CAS  PubMed  Google Scholar 

  90. Kindberg E, Akerlind B, Johnsen C, et al (2007) Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark. J Clin Microbiol 45(8):2720–2722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kindberg E, Hejdeman B, Bratt G, et al (2006) A nonsense mutation (428G→A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection. AIDS 20(5):685–689

    Article  CAS  PubMed  Google Scholar 

  92. Brasch F, Ochs M, Kähne T, et al (2003) Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung. J Biol Chem 278(49):49006–49014

    Article  CAS  PubMed  Google Scholar 

  93. Chuman Y, Bergman A, Ueno T, et al (1999) Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas. FEBS Lett 462(1–2):129–134

    Article  CAS  PubMed  Google Scholar 

  94. Zhang Q, Bastard P, Liu Z, et al (2020) Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370(6515). https://doi.org/10.1126/science.abd4570

  95. Hoffmann M, Kleine-Weber H, Schroeder S, et al (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 181(2):271–80.e8. https://doi.org/10.1016/j.cell.2020.02.052

  96. Russo R, Andolfo I, Lasorsa VA, et al (2020) Genetic Analysis of the Coronavirus SARS-CoV-2 Host Protease TMPRSS2 in Different Populations. Front Genet 11:872. https://doi.org/10.3389/fgene.2020.00872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Andolfo I, Russo R, Lasorsa VA, et al (2021) Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19. iScience 24(4):102322. https://doi.org/10.1016/j.isci.2021.102322

  98. Hou Y, Zhao J, Martin W, et al (2020) New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Medicine 18(1):216. https://doi.org/10.1186/s12916-020-01673-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Vishnubhotla R, Vankadari N, Ketavarapu V, et al. Genetic variants in TMPRSS2 and Structure of SARS-CoV-2 spike glycoprotein and TMPRSS2 complex. bioRxiv; 2020.

    Google Scholar 

  100. Zhou P, Yang XL, Wang XG, et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798):270–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Chen L, Zheng S (2020) Understand variability of COVID-19 through population and tissue variations in expression of SARS-CoV-2 host genes. Inform Med Unlocked 21:100443. https://doi.org/10.1016/j.imu.2020.100443

    Article  PubMed  PubMed Central  Google Scholar 

  102. Martínez-Sanz J, Jiménez D, Martínez-Campelo L, et al (2021) Role of ACE2 genetic polymorphisms in susceptibility to SARS-CoV-2 among highly exposed but non infected healthcare workers. Emerg Microbes Infect 10(1):493–496

    Article  PubMed  PubMed Central  Google Scholar 

  103. Poulas K, Farsalinos K, Zanidis C (2020) Activation of TLR7 and Innate Immunity as an Efficient Method Against COVID-19 Pandemic: Imiquimod as a Potential Therapy. Front Immunol 11. https://doi.org/10.3389/fimmu.2020.01373.

  104. van der Made CI, Simons A, Schuurs-Hoeijmakers J, et al (2020) Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA 324(7):663–673

    Article  PubMed  Google Scholar 

  105. Fallerini C, Daga S, Mantovani S, et al (2021) Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study. Elife 10:e67569. https://doi.org/10.7554/eLife.67569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Asano T, Boisson B, Onodi F, et al (2021) X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci Immunol 6(62):eabl4348. https://doi.org/10.1126/sciimmunol.abl4348

  107. Solanich X, Vargas-Parra G, van der Made CI, et al (2021) Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19. Front Immunol 12. https://doi.org/10.3389/fimmu.2021.719115

  108. Kosmicki JA, Horowitz JE, Banerjee N, et al (2021) A catalog of associations between rare coding variants and COVID-19 outcomes. medRxiv 2020.10.28.20221804. https://doi.org/10.1101/2020.10.28.20221804

  109. Butler-Laporte G, Povysil G, Kosmicki JA, et al (2022) Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative. medRxiv 2022.03.28.22273040. https://doi.org/10.1101/2022.03.28.22273040

  110. Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5(1):58–68

    Article  CAS  PubMed  Google Scholar 

  111. Hsieh MH, Beirag N, Murugaiah V, et al (2021) Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles. Front Immunol 12. https://doi.org/10.3389/fimmu.2021.641360.

  112. Seibold MA, Wise AL, Speer MC, et al (2011) A Common MUC5B Promoter Polymorphism and Pulmonary Fibrosis. N Eng J Med 364(16):1503–1512

    Article  CAS  Google Scholar 

  113. Peljto AL, Zhang Y, Fingerlin TE, et al (2013) Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 309(21):2232–2239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Fadista J, Kraven LM, Karjalainen J, et al (2021) Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity. EBioMedicine 65:103277. https://doi.org/10.1016/j.ebiom.2021.103277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Roy MG, Livraghi-Butrico A, Fletcher AA, et al (2014) Muc5b is required for airway defence. Nature 505(7483):412–416

    Article  CAS  PubMed  Google Scholar 

  116. van Moorsel CHM, van der Vis JJ, Duckworth A, et al. The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population. Front Med. 2021;8:668024.

    Article  Google Scholar 

  117. Blackwell JM, Jamieson SE, Burgner D (2009) HLA and infectious diseases. Clin Microbiol Rev 22(2):370–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Vietzen H, Zoufaly A, Traugott M, et al (2021) Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19. Genet Med 23(5):963–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Nguyen A, David JK, Maden SK, et al (2020) Human leukocyte antigen susceptibility map for SARS-CoV-2. medRxiv 2020.03.22.20040600. https://doi.org/10.1101/2020.03.22.20040600.

  120. Barmania F, Mellet J, Ryder MA, et al (2022) Coronavirus Host Genetics South Africa (COHG-SA) database-a variant database for gene regions associated with SARS-CoV-2 outcomes. Eur J Hum Genet 30(8):880–888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. van Rooij JGJ, Jhamai M, Arp PP, et al (2017) Population-specific genetic variation in large sequencing data sets: why more data is still better. Eur J Hum Genet 25(10):1173–1175

    Article  PubMed  PubMed Central  Google Scholar 

  122. Adeyemo A, Rotimi C (2010) Genetic Variants Associated with Complex Human Diseases Show Wide Variation across Multiple Populations. Public Health Genomics 13(2):72–79

    Article  CAS  PubMed  Google Scholar 

  123. Ni Q, Chen X, Zhang P, et al (2022) Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians. Orphanet J Rare Dis 17(1):129. https://doi.org/10.1186/s13023-022-02279-9

    Article  PubMed  PubMed Central  Google Scholar 

  124. Tanaka H, Lee H, Morita A, et al (2021) Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19. Int J Infect Dis 113:74–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Ortiz-Fernández L, Sawalha AH (2020) Genetic variability in the expression of the SARS-CoV-2 host cell entry factors across populations. Genes Immun 21(4):269–272

    Article  PubMed  PubMed Central  Google Scholar 

  126. Wang N, Zhan Y, Zhu L, et al (2020) Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host Microbe 28(3):455–64.e2. https://doi.org/10.1016/j.chom.2020.07.005

  127. Marconi VC, Ramanan AV, de Bono S, et al (2021) Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med 9(12):1407–1418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Kalil AC, Patterson TF, Mehta AK, et al (2020) Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Eng J Med 384(9):795–807

    Article  Google Scholar 

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Acknowledgments

This work has been supported by the South African Medical Research Council (SAMRC) Extramural Unit for Stem Cell Research and Therapy and the University of Pretoria through the Institute for Cellular and Molecular Medicine. This work has also been supported through funding by the SAMRC through its Division of Research Capacity Development under the Internship Scholarship Program from funding received from the Public Health Enhancement Fund/South African National Department of Health. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC.

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  1. Institute for Cellular and Molecular Medicine, Department of Immunology, SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Fatima Barmania, Juanita Mellet, Megan A. Holborn & Michael S. Pepper

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  1. Fatima Barmania
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  2. Juanita Mellet
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  3. Megan A. Holborn
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  4. Michael S. Pepper
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Correspondence to Michael S. Pepper .

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  1. University of Campinas, Campinas, São Paulo, Brazil

    Paul C. Guest

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Barmania, F., Mellet, J., Holborn, M.A., Pepper, M.S. (2023). Genetic Associations with Coronavirus Susceptibility and Disease Severity. In: Guest , P.C. (eds) Application of Omic Techniques to Identify New Biomarkers and Drug Targets for COVID-19. Advances in Experimental Medicine and Biology(), vol 1412. Springer, Cham. https://doi.org/10.1007/978-3-031-28012-2_6

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