Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population
Abstract Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral and host factors. These findings have highlighted th...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57982-3 |
| _version_ | 1797209424457105408 |
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| author | Mariana Angulo-Aguado Juan Camilo Carrillo-Martinez Nora Constanza Contreras-Bravo Adrien Morel Katherine Parra-Abaunza William Usaquén Dora Janeth Fonseca-Mendoza Oscar Ortega-Recalde |
| author_facet | Mariana Angulo-Aguado Juan Camilo Carrillo-Martinez Nora Constanza Contreras-Bravo Adrien Morel Katherine Parra-Abaunza William Usaquén Dora Janeth Fonseca-Mendoza Oscar Ortega-Recalde |
| author_sort | Mariana Angulo-Aguado |
| collection | DOAJ |
| description | Abstract Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral and host factors. These findings have highlighted the potential of host genetic markers to identify high-risk individuals and develop target interventions to reduce morbimortality. Despite its importance, genetic host factors remain largely understudied in Latin-American populations. Using a case–control design and a custom next-generation sequencing (NGS) panel encompassing 81 genetic variants and 74 genes previously associated with COVID-19 severity and long-COVID, we analyzed 56 individuals with asymptomatic or mild COVID-19 and 56 severe and critical cases. In agreement with previous studies, our results support the association between several clinical variables, including male sex, obesity and common symptoms like cough and dyspnea, and severe COVID-19. Remarkably, thirteen genetic variants showed an association with COVID-19 severity. Among these variants, rs11385942 (p < 0.01; OR = 10.88; 95% CI = 1.36–86.51) located in the LZTFL1 gene, and rs35775079 (p = 0.02; OR = 8.53; 95% CI = 1.05–69.45) located in CCR3 showed the strongest associations. Various respiratory and systemic symptoms, along with the rs8178521 variant (p < 0.01; OR = 2.51; 95% CI = 1.27–4.94) in the IL10RB gene, were significantly associated with the presence of long-COVID. The results of the predictive model comparison showed that the mixed model, which incorporates genetic and non-genetic variables, outperforms clinical and genetic models. To our knowledge, this is the first study in Colombia and Latin-America proposing a predictive model for COVID-19 severity and long-COVID based on genomic analysis. Our study highlights the usefulness of genomic approaches to studying host genetic risk factors in specific populations. The methodology used allowed us to validate several genetic variants previously associated with COVID-19 severity and long-COVID. Finally, the integrated model illustrates the importance of considering genetic factors in precision medicine of infectious diseases. |
| first_indexed | 2024-04-24T09:54:29Z |
| format | Article |
| id | doaj.art-91b5947607cd453c866192058358b1ca |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T09:54:29Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-91b5947607cd453c866192058358b1ca2024-04-14T11:14:24ZengNature PortfolioScientific Reports2045-23222024-04-0114111710.1038/s41598-024-57982-3Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian populationMariana Angulo-Aguado0Juan Camilo Carrillo-Martinez1Nora Constanza Contreras-Bravo2Adrien Morel3Katherine Parra-Abaunza4William Usaquén5Dora Janeth Fonseca-Mendoza6Oscar Ortega-Recalde7School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del RosarioSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del RosarioSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del RosarioSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del RosarioHospital Universitario Mayor - Méderi - Universidad del RosarioPopulations Genetics and Identification Group, Institute of Genetics, Universidad Nacional de ColombiaSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del RosarioSchool of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del RosarioAbstract Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral and host factors. These findings have highlighted the potential of host genetic markers to identify high-risk individuals and develop target interventions to reduce morbimortality. Despite its importance, genetic host factors remain largely understudied in Latin-American populations. Using a case–control design and a custom next-generation sequencing (NGS) panel encompassing 81 genetic variants and 74 genes previously associated with COVID-19 severity and long-COVID, we analyzed 56 individuals with asymptomatic or mild COVID-19 and 56 severe and critical cases. In agreement with previous studies, our results support the association between several clinical variables, including male sex, obesity and common symptoms like cough and dyspnea, and severe COVID-19. Remarkably, thirteen genetic variants showed an association with COVID-19 severity. Among these variants, rs11385942 (p < 0.01; OR = 10.88; 95% CI = 1.36–86.51) located in the LZTFL1 gene, and rs35775079 (p = 0.02; OR = 8.53; 95% CI = 1.05–69.45) located in CCR3 showed the strongest associations. Various respiratory and systemic symptoms, along with the rs8178521 variant (p < 0.01; OR = 2.51; 95% CI = 1.27–4.94) in the IL10RB gene, were significantly associated with the presence of long-COVID. The results of the predictive model comparison showed that the mixed model, which incorporates genetic and non-genetic variables, outperforms clinical and genetic models. To our knowledge, this is the first study in Colombia and Latin-America proposing a predictive model for COVID-19 severity and long-COVID based on genomic analysis. Our study highlights the usefulness of genomic approaches to studying host genetic risk factors in specific populations. The methodology used allowed us to validate several genetic variants previously associated with COVID-19 severity and long-COVID. Finally, the integrated model illustrates the importance of considering genetic factors in precision medicine of infectious diseases.https://doi.org/10.1038/s41598-024-57982-3COVID-19Long-COVIDNext-generation sequencingPredictive modelPersonalized medicine |
| spellingShingle | Mariana Angulo-Aguado Juan Camilo Carrillo-Martinez Nora Constanza Contreras-Bravo Adrien Morel Katherine Parra-Abaunza William Usaquén Dora Janeth Fonseca-Mendoza Oscar Ortega-Recalde Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population Scientific Reports COVID-19 Long-COVID Next-generation sequencing Predictive model Personalized medicine |
| title | Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population |
| title_full | Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population |
| title_fullStr | Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population |
| title_full_unstemmed | Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population |
| title_short | Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population |
| title_sort | next generation sequencing of host genetics risk factors associated with covid 19 severity and long covid in colombian population |
| topic | COVID-19 Long-COVID Next-generation sequencing Predictive model Personalized medicine |
| url | https://doi.org/10.1038/s41598-024-57982-3 |
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