Association between Human Leukocyte Antigen (HLA) DQB1*06 and HLA DQB1*03 and adverse outcomes in a group of critically ill patients with COVID-19 in Tunisia: a cross-sectional study.

Introduction: Human Leukocyte Antigen (HLA) system is a highly polymorphic genetic system associated with the prognosis of several infectious diseases. The aim of this study is to investigate the association of HLA polymorphism with the outcome of coronavirus disease 2019 (COVID-19) in Tunisian critically ill patients.

Methods: this retrospective cross-sectional study included 42 consecutive patients hospitalized in intensive care unit (ICU) for COVID-19 in March 2021. Genotyping of HLA loci was performed by LABType™ sequence-specific oligonucleotide (SSO) typing kits (One lambda Inc, USA). Statistical analyses were performed using Statistical Package for Social Sciences (SPSS®) version 23.0. A p-value <0.05 was considered significant. Multivariable regression analysis was performed for the association between HLA polymorphism with adverse outcomes with adjustment for potential confounders such as age, sex, co-morbidities and blood type.

Results: patients included in our study had a mean age of 64.5 ± 11.5 (34-83) years and were mainly men (64.3%; (n=27)). The most common cardiovascular risk factors were obesity (61.9%; (n=26)) and hypertension (26.2%; (n=11)). Thirty-two patients died (76.2%). Eleven patients (26.2%) required intubation during hospitalization. We found that HLA DQB1*06 allele was significantly associated with protection against mortality aOR: 0.066, 95% CI 0.005-0.821; p = 0.035. HLA DQB1*03 allele was significantly associated with protection against intubation aOR: 0.151, 95% CI 0.023-0.976; p = 0.047.

Conclusion: it was found that there are 2 protective HLA alleles against COVID-19 severity and mortality in critically ill patients. This could allow focusing on people genetically predisposed to develop severe forms of COVID-19.