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Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis
BACKGROUND: The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. METHODS: By combining the predictive power of multiple in silico HLA predictors, we have previously identified prevalent HLA c...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605564/ https://www.ncbi.nlm.nih.gov/pubmed/33140057 http://dx.doi.org/10.1101/2020.10.27.20220863 |
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author | Warren, René L. Birol, Inanç |
author_facet | Warren, René L. Birol, Inanç |
author_sort | Warren, René L. |
collection | PubMed |
description | BACKGROUND: The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. METHODS: By combining the predictive power of multiple in silico HLA predictors, we have previously identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small cohorts at the COVID-19 pandemic onset. Since then, newer and larger patient cohorts with controls and associated demographic and clinical data have been deposited in public repositories. Here, we report on HLA-I and HLA-II alleles, along with their associated risk significance in one such cohort of 126 patients, including COVID-19 positive (n=100) and negative patients (n=26). RESULTS: We recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes reveal nominally significant risk associations with A*11:01 (FET p=0.0078), C*04:01 (FET p=0.0087) and DQA1*01:02 (FET p=0.0121). CONCLUSIONS: While enrichment of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with the latter three alleles tend to fare worse overall. This is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0023), and may hold potential clinical value. |
format | Online Article Text |
id | pubmed-7605564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-76055642020-11-03 Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis Warren, René L. Birol, Inanç medRxiv Article BACKGROUND: The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. METHODS: By combining the predictive power of multiple in silico HLA predictors, we have previously identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small cohorts at the COVID-19 pandemic onset. Since then, newer and larger patient cohorts with controls and associated demographic and clinical data have been deposited in public repositories. Here, we report on HLA-I and HLA-II alleles, along with their associated risk significance in one such cohort of 126 patients, including COVID-19 positive (n=100) and negative patients (n=26). RESULTS: We recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes reveal nominally significant risk associations with A*11:01 (FET p=0.0078), C*04:01 (FET p=0.0087) and DQA1*01:02 (FET p=0.0121). CONCLUSIONS: While enrichment of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with the latter three alleles tend to fare worse overall. This is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0023), and may hold potential clinical value. Cold Spring Harbor Laboratory 2020-11-02 /pmc/articles/PMC7605564/ /pubmed/33140057 http://dx.doi.org/10.1101/2020.10.27.20220863 Text en http://creativecommons.org/licenses/by/4.0/It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Warren, René L. Birol, Inanç Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis |
title | Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis |
title_full | Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis |
title_fullStr | Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis |
title_full_unstemmed | Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis |
title_short | Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis |
title_sort | retrospective in silico hla predictions from covid-19 patients reveal alleles associated with disease prognosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605564/ https://www.ncbi.nlm.nih.gov/pubmed/33140057 http://dx.doi.org/10.1101/2020.10.27.20220863 |
work_keys_str_mv | AT warrenrenel retrospectiveinsilicohlapredictionsfromcovid19patientsrevealallelesassociatedwithdiseaseprognosis AT birolinanc retrospectiveinsilicohlapredictionsfromcovid19patientsrevealallelesassociatedwithdiseaseprognosis |