HLA alleles measured from COVID-19 patient transcriptomes reveal associations with disease prognosis in a New York cohort.

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. Previously, we have identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small patient cohorts at the COVID-19 pandemic onset.

METHODS

We have since analyzed a larger public patient cohort data ( = 126 patients) with controls, associated demographic and clinical data. By combining the predictive power of multiple HLA predictors, we report on HLA-I and HLA-II alleles, along with their associated risk significance.

RESULTS

We observe HLA-II DPA102:02 at a higher frequency in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher's exact test [FET]  = 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, including admission to intensive care, reveal nominally significant risk associations with A11:01 (FET  = 0.0078) and C04:01 (FET  = 0.0087). The association with severe disease outcome is especially evident for patients with C04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni  = 0.0323). While prevalence of some of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with HLA-I C*04:01 tend to fare worse overall. This HLA allele may hold potential clinical value.