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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...

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Detalles Bibliográficos
Autores principales: Warren, René L., Birol, Inanç
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
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
Descripción
Sumario: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.