Highlights • 40 candidate genes might be associated with severe COVID-19. • Inflammasome (NLRP1) as a possible cause of cytokine storm in COVID-19. • IL-18, CCR1, CCR9 and EndoU(coronavirus protein) inhibition as possible treatment for COVID-19. • DC-SIGN (Lectin pathway) and MxA expression might explain SARS-CoV-2 latency and reactivation in some cases. • Case report as study design for discovering novel monogenic cases(with low minor allele frequency) of severe COVID-19. Background Susceptibility to severe viral infections was reported to be associated with genetic variants in immune response genes using case reports and GWAS studies. SARS-CoV-2 is an emergent viral disease that caused millions of COVID-19 cases all over the world. Around 15 % of cases are severe and some of them are accompanied by dysregulated immune system and cytokine storm. There is increasing evidence that severe manifestations of COVID-19 might be attributed to human genetic variants in genes related to immune deficiency and or inflammasome activation (cytokine storm). Objective Identify the candidate genes that are likely to aid in explaining severe COVID-19 and provide insights to understand the pathogenesis of severe COVID-19. Methods In this article, we systematically reviewed genes related to viral susceptibility that were reported in human genetic studies (Case-reports and GWAS) to understand the role of host viral interactions and to provide insights into the pathogenesis of severe COVID-19. Results We found 40 genes associated with viral susceptibility and 21 of them were associated with severe SARS-CoV disease and severe COVID-19. Some of those genes were implicated in TLR pathways, others in C-lectin pathways, and others were related to inflammasome activation (cytokine storm). Conclusion This compilation represents a list of candidate genes that are likely to aid in explaining severe COVID-19 which are worthy of inclusion in gene panels and during meta-analysis of different variants in host genetics studies of COVID-19. In addition, we provide several hypotheses for severe COVID-19 and possible therapeutic targets.
【저자키워드】 COVID-19, Cytokine storm, coronavirus, Interleukins, host genetics, interferon, lactate dehydrogenase, COVID-19 pathogenesis, Peripheral blood mononuclear cells, Inflammasome, SARS Coronavirus, inborn errors of immunity, SARS coronavirus 2, GWAS, genome wide association studies, SARS-CoV-2, SARS Coronavirus 2, SARS-CoV, SARS Coronavirus, IUIS, International Union of Immunological Societies, OMIM, Online Mendelian Inheritance in Man (OMIM), HSE, herpses simplex encephalitis, HSV-1, Herpes Simplex Virus 1, MeSH, medical subject heading, dsRNA, double-strand RNA, DC-SIGN, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin, LDH, lactate dehydrogenase, IL-18BP, IL-18 binding protein, PBMCs, peripheral blood mononuclear cells, endoU, coronavirus endoribonuclease, SARS-coronavirus 2, C-lectin pathways, TLR pathway, Host immune defenses, COVID-19 GWAS, Viral susceptibility, GWASgenome wide association studies, genome wide association studies, SARS-CoV-2SARS Coronavirus 2, SARS-CoVSARS Coronavirus, IUISInternational Union of Immunological Societies, International Union of Immunological Societies, OMIMOnline Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Man (OMIM), HSEherpses simplex encephalitis, herpses simplex encephalitis, HSV-1Herpes Simplex Virus 1, Herpes Simplex Virus 1, MeSHmedical subject heading, medical subject heading, dsRNAdouble-strand RNA, double-strand RNA, DC-SIGNDendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin, LDHlactate dehydrogenase, IL-18BPIL-18 binding protein, IL-18 binding protein, PBMCsperipheral blood mononuclear cells, endoUcoronavirus endoribonuclease, coronavirus endoribonuclease, 【초록키워드】 Meta-analysis, SARS-CoV-2, viral infection, Pathogenesis, severe COVID-19, SARS-CoV, susceptibility, variant, immune system, immune, Case report, Protein, pathway, Study design, viral disease, Genetic variant, GWAS, latency, minor allele frequency, disease, expression, therapeutic targets, Evidence, Interaction, Pathways, candidate gene, lectin, manifestation, DC-SIGN, immune response gene, deficiency, COVID-19 case, inflammasome activation, CCR1, genetic study, IL-18, CCR9, Host, Inclusion, objective, NLRP1, Result, caused, reported, addition, dysregulated, implicated, explain, hypothese, accompanied, TLR pathways, treatment for COVID-19, 【제목키워드】 viral infection, susceptibility, Human, systematic review,