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Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification.
Front Immunol. 2021; 12:653489.FI

Abstract

The ongoing COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2 has affected all aspects of human society with a special focus on healthcare. Although older patients with preexisting chronic illnesses are more prone to develop severe complications, younger, healthy individuals might also exhibit serious manifestations. Previous studies directed to detect genetic susceptibility factors for earlier epidemics have provided evidence of certain protective variations. Following SARS-CoV-2 exposure, viral entry into cells followed by recognition and response by the innate immunity are key determinants of COVID-19 development. In the present review our aim was to conduct a thorough review of the literature on the role of single nucleotide polymorphisms (SNPs) as key agents affecting the viral entry of SARS-CoV-2 and innate immunity. Several SNPs within the scope of our approach were found to alter susceptibility to various bacterial and viral infections. Additionally, a multitude of studies confirmed genetic associations between the analyzed genes and autoimmune diseases, underlining the versatile immune consequences of these variants. Based on confirmed associations it is highly plausible that the SNPs affecting viral entry and innate immunity might confer altered susceptibility to SARS-CoV-2 infection and its complex clinical consequences. Anticipating several COVID-19 genomic susceptibility loci based on the ongoing genome wide association studies, our review also proposes that a well-established polygenic risk score would be able to clinically leverage the acquired knowledge.

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Authors+Show Affiliations

Grolmusz VK
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. Hereditary Tumors Research Group, Eötvös Loránd Research Network-Semmelweis University, Budapest, Hungary.
Bozsik A
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. Hereditary Tumors Research Group, Eötvös Loránd Research Network-Semmelweis University, Budapest, Hungary.
Papp J
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. Hereditary Tumors Research Group, Eötvös Loránd Research Network-Semmelweis University, Budapest, Hungary.
Patócs A
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. Hereditary Tumors Research Group, Eötvös Loránd Research Network-Semmelweis University, Budapest, Hungary. Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary.

MeSH

COVID-19Genetic Predisposition to DiseaseGerm CellsHumansImmunity, InnateMultifactorial InheritanceSARS-CoV-2Virus Internalization

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

33763088

Citation

Grolmusz, Vince Kornél, et al. "Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification." Frontiers in Immunology, vol. 12, 2021, p. 653489.
Grolmusz VK, Bozsik A, Papp J, et al. Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification. Front Immunol. 2021;12:653489.
Grolmusz, V. K., Bozsik, A., Papp, J., & Patócs, A. (2021). Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification. Frontiers in Immunology, 12, 653489. https://doi.org/10.3389/fimmu.2021.653489
Grolmusz VK, et al. Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification. Front Immunol. 2021;12:653489. PubMed PMID: 33763088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification. AU - Grolmusz,Vince Kornél, AU - Bozsik,Anikó, AU - Papp,János, AU - Patócs,Attila, Y1 - 2021/03/08/ PY - 2021/01/14/received PY - 2021/02/16/accepted PY - 2021/3/25/entrez PY - 2021/3/26/pubmed PY - 2021/4/7/medline KW - COVID-19 KW - SARS-CoV-2 KW - genetic susceptibility KW - genotype-phenotype association studies KW - innate immunity KW - polygenic risk score KW - risk stratification KW - viral entry SP - 653489 EP - 653489 JF - Frontiers in immunology JO - Front Immunol VL - 12 N2 - The ongoing COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2 has affected all aspects of human society with a special focus on healthcare. Although older patients with preexisting chronic illnesses are more prone to develop severe complications, younger, healthy individuals might also exhibit serious manifestations. Previous studies directed to detect genetic susceptibility factors for earlier epidemics have provided evidence of certain protective variations. Following SARS-CoV-2 exposure, viral entry into cells followed by recognition and response by the innate immunity are key determinants of COVID-19 development. In the present review our aim was to conduct a thorough review of the literature on the role of single nucleotide polymorphisms (SNPs) as key agents affecting the viral entry of SARS-CoV-2 and innate immunity. Several SNPs within the scope of our approach were found to alter susceptibility to various bacterial and viral infections. Additionally, a multitude of studies confirmed genetic associations between the analyzed genes and autoimmune diseases, underlining the versatile immune consequences of these variants. Based on confirmed associations it is highly plausible that the SNPs affecting viral entry and innate immunity might confer altered susceptibility to SARS-CoV-2 infection and its complex clinical consequences. Anticipating several COVID-19 genomic susceptibility loci based on the ongoing genome wide association studies, our review also proposes that a well-established polygenic risk score would be able to clinically leverage the acquired knowledge. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/33763088/Germline_Genetic_Variants_of_Viral_Entry_and_Innate_Immunity_May_Influence_Susceptibility_to_SARS_CoV_2_Infection:_Toward_a_Polygenic_Risk_Score_for_Risk_Stratification_ DB - PRIME DP - Unbound Medicine ER -