Immunogenetic Predisposition to SARS-CoV-2 Infection

Simple Summary Since the beginning of the SARS-CoV-2 pandemic in 2020, numerous data with respect to the influence of immunogenetics on the predisposition to and severity of infection have been reported worldwide (PubMed; n = 228; 6 November 2022). Immunogenetics play a pivotal role in infection, vaccination, its failures, and/or vaccination breakthrough. Factors including the major histocompatibility complex and the common ABO blood group system have been discussed. Herein, we describe the association of HLA-A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1, DPB1, and HLA-E, F, G, and H on the results of molecular detection of COVID-19, or, in some cases, on antibody detection upon first testing. Furthermore, we molecularly defined 22 blood group systems comprising 26 genes and 5 platelet antigen genes. Herein, 37% tested COVID-19 negative while 63% tested positive by PCR. Within the negative subjects, HLA-B*57:01, HLA-B*55:01, DRB1*13:01, and DRB1*01:01, were enriched, and in the positive group, homozygosity for DQA/DQB, DRB1*09:01, and DRB1*15:01 was observed. For HLA-DQA1, we observed an enrichment for DQA1*01:01, DQA1*02:01, and DQA1*01:03. For HLA-DQB1, we found that HLA-DQB1*06:02 was enriched in the positive group, while HLA-DQB1*05:01 and HLA-DQB1*06:03 were enriched in the negative group. The homozygous platelet antigen HPA-1a was significantly enriched in the negative group, contrasting with the HPA-1ab, which was enriched in the COVID-19 infected group. Herein, we included 527 individuals from two Hospitals, Chemnitz and University-Hospital Leipzig. In total, 199 were negative for PCR and 328 were positive upon first admission. We used next generation sequencing for HLA-A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1, and DPB1, and in some cases, HLA-E, F, G, and H. Furthermore, we molecularly defined 22 blood group systems comprising 26 genes and 5 platelet antigen genes. We observed a significant enrichment of homozygosity for DQA/DQB in the positive group. Within the negative subjects, HLA-B*57:01, HLA-B*55:01, DRB1*13:01, and DRB1*01:01 were enriched, and in the positive group, homozygosity for DQA/DQB, DRB1*09:01, and DRB1*15:01 was observed. DQA1*01:01, DQA1*02:01, and DQA1*01:03 were enriched in the negative group. HLA-DQB1*06:02 was enriched in the positive group, and HLA-DQB1*05:01 and HLA-DQB1*06:03 were enriched in the negative group. For the blood group systems MNS, RH, LE, FY, JK, YT, DO, and KN, enrichment was seen in both groups, depending on the antigen under observation. Homozygosity for D-positive RHD alleles, as well as the phenotypes M-N+ of the MNS blood group system and Yk(a-) of the KN system, were enriched in the positive group. All of these significances disappeared upon correction. Subjects who carried homozygous HPA-1a were more frequent in the negative group, contrasting with the finding that HPA-1ab was enriched in the positive group.