Association of Human Leukocyte Antigen Alleles with COVID-19 Severity and Mortality in a Spanish Population

Background and Objectives: The aim of the following cross-sectional study is to determine the association between human leukocyte antigen (HLA) alleles and outcomes in patients presenting to the emergency department (ED) with SARS-CoV-2 infection. Methods and Materials: Genotyping was made using the Axiom Human Genotyping SARS-CoV-2 Research Array. Statistical analysis was made with Fisher's exact test and multivariable logistic regression, adjusted for sex, age and clinical variables. Results: Of 190 patients, 11.1% were discharged from the ED; 57.9% were admitted to the COVID-19 ward, without intensive care unit (ICU) admission; 15.3% survived an ICU admission; and 15.8% died. After multivariable analysis, two HLA alleles protected against hospital admission (HLA-C*05:01, adjusted odds ratio [aOR] 0.2, 95% confidence interval [CI] 0.055-0.731; and HLA-DQB1*02:02, aOR 0.046, CI 0.002-0.871) and one was associated with higher risk for ICU admission or death (HLA-DQA1*05:01, aOR 2.517, CI 1.086-5.833). Conclusions: In this population, HLA-C*05:01 and HLA-DQB1*02:02 are associated with a protective effect against hospital admission and HLA-DQA1*05:01 is associated with higher risk of ICU admission or death in the multivariable analysis. This may help stratify risk in COVID-19 patients.