Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis

BackgroundThe Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. MethodsBy 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). ResultsWe recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fishers exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohorts 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). ConclusionsWhile 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.