A3.0: The role of the HLA allelic repository on the clinical severity of COVID-19

Aim: Amidst the coronavirus disease 2019 (COVID-19) pandemic, there has been a rapid expansion in the scientific literature for the identification of unique patient host variables that influence the propensity for a severe clinical course when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen (HLA) alleles have been implicated as an underlying determinant for modulating the immune response to SARS-CoV-2. Therefore, we aimed to determine the association of patients’ genetic profiles via HLA typing and correlate it with the disease severity of COVID-19 infection.

Methods: This prospective study was conducted on 61 COVID-19 patients admitted in Saskatoon, Canada between March and December 2020. Next-generation sequencing was performed on the patients’ blood samples to obtain high-resolution HLA typing profiles. These profiles were compared against the saskatoon HLA allelic repository (N=1000) and against the low severity group. Statistical analysis was performed in SPSS 28.

Results: In the HLA‐BW4 group, compared to the background HLA allele frequency in Saskatoon, B*51:02 (15.2%) was 2.4-fold higher (p-value 0.0004), and 4.9-fold higher in the high severity COVID-19 group. Similarly, A*24:02 (17.4%) was 1.96-fold higher (p-value 0.004) than the background HLA allelic frequency in Saskatoon and 1.4-fold higher than the low severity COVID-19 group. Both A*24:02 and B*51:02 have isoleucine in position 80 which has a stronger affinity to the KIR3DL inhibitory NK cells. Compared to the background HLA allele frequency in Saskatoon, B*15:01 (17.4%) was 3.05-fold higher (p-value <0.00001) and compared to the low severity COVID-19 group was 1.87-fold higher.

Conclusions: These results suggest that Killer immunoglobulin-like receptors (KIR) associated with specific HLA groups such as BW4 are involved in eluding the natural killer (NK) cells mediated surveillance of SARS-CoV-2. These alleles appear prominently in the HLA allelic repository in the severe COVID-19 group focusing on the importance of NK cells in the convalescence of COVID-19.