Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells. In the present manuscript, we explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death. HLA-A, HLA-B, and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with next-generation sequencing. Deceased patients were split into two groups according to age at the time of death: n = 26 adult patients aged below 60 and n = 85 elderly patients over 60. With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual. The resulting RS was significantly higher in the group of deceased adults compared to elderly adults [ p = 0.00348, area under the receiver operating characteristic curve ( AUC ROC = 0.68)]. In particular, presence of HLA-A * 01:01 allele was associated with high risk, while HLA-A * 02:01 and HLA-A * 03:01 mainly contributed to low risk. The analysis of patients with homozygosity strongly highlighted these results: homozygosity by HLA-A * 01:01 accompanied early deaths, while only one HLA-A * 02:01 homozygote died before 60 years of age. Application of the constructed RS model to an independent Spanish patients cohort ( n = 45) revealed that the score was also associated with the severity of the disease. The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, MHC class I, HLA class I, peptide presentation, 【초록키워드】 viral infection, coronavirus, immune response, T cells, severity, Russia, human leukocyte antigen, peptide, risk, Cohort, ROC, Next-generation sequencing, Patient, Genotype, death, age, HLA, application, genotypes, characteristic, Critical, HLA-B, Analysis, Deceased, deaths, Elderly patient, AUC, high risk, HLA-A, connection, acute respiratory syndrome, allele, HLA-C, manuscript, Volunteer, Cell, independent, Course, resulting, died, the disease, significantly higher, contributed, two group, presenting, homozygote, accompanied, patients with COVID-19, Spanish patient, viral peptide, 【제목키워드】 HLA, class,