HLA‐A homozygosis is associated with susceptibility to COVID‐19

Abstract

The purpose of this single center retrospective study was to investigate the relationship between HLA and ABO polymorphisms and COVID‐19 susceptibility and severity in kidney transplant recipients. It included 720 recipients who had COVID‐19 and 1680 controls composed by recipients in follow‐up who did not contact the transplantation center for COVID‐19 symptoms, up to the moment of their inclusion in the study. HLA‐A, ‐B, and ‐DRB1 allele groups and ABO frequencies were compared between recipients with COVID‐19 (all cases, or separately mild/moderate and severe disease) and controls. The HLA association study was conducted in two case–control series and only associations that showed a p‐value <0.05 in both series were considered. No HLA association regarding COVID‐19 occurrence or severity met this criterion. Homozygosity at HLA‐A locus was associated with COVID‐19 susceptibility (odds ratio 1.4) but not severity. Blood groups A and O were associated with susceptibility and resistance to COVID‐19, respectively. COVID‐19 severity was associated only with older age and cardiac disease, in a multivariate analysis. We conclude that an influence of HLA on COVID‐19 susceptibility is supported by the association with homozygosity at HLA‐A locus but that there is no evidence for a role of any particular HLA‐A, ‐B, or ‐DRB1 polymorphism. Thus, we suggest that what matters is the overall capability of an individual's HLA molecules to present SARS‐CoV‐2 peptides to T cells, a factor that might have a great influence on the breadth of the immune response.

Time-Dependent Molecular Motifs of Pulmonary Fibrogenesis in COVID-19

“…The following are available online at https://www.mdpi.com/article/10 .3390/ijms23031583/s1. References [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] are cited in the Supplementary Materials. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.…”

Distribution of HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 allele frequencies in patients with COVID-19 bilateral pneumonia in Russians, living in the Chelyabinsk region (Russia)

“…In studies carried out in a Brazilian population [16] , a higher susceptibility was shown for the individuals who were homozygous for the entire HLA-A locus.…”

Association of HLA gene polymorphism with susceptibility, severity, and mortality of COVID‐19: A systematic review

“…Six types of approaches were observed when it came to data sourcing for analysis, including both dry lab and wet lab, which are briefly discussed here—(i) HLA typing for both patient and control group were carried out in wet lab, frequency of different alleles were compared between two groups for any significant differences with different outcomes ( n = 9) 2,14,17,18,25,27,29,31,42 ; (ii) the most frequent HLA alleles were retrieved from AFND for the concerned countries of respected studies, SARS‐CoV‐2 genome was downloaded from NCBI or national databases and peptide binding capacity of frequent alleles was then evaluated using different version of NetMHCpan web server, association of strongly or weakly bound peptides with COVID cases and deaths per million (from worldometer, WHO situation report) were analyzed further through frequency analysis of HLA alleles, as it is established that strongly bound peptide are better presented and weakly bound peptides are poorly presented by MHC to T‐cells and thus can play a major role in adequate immune responses against COVID ( n = 6) 12,13,19–22 ; (iii) HLA allele frequency data for both patient and control group were obtained from national organ donor registry and COVID data from worldometer or national COVID registry, compared allele frequency between healthy and COVID group for identifying any association with COVID susceptibility or among mild, moderate or severe groups of COVID patients to associate HLA with COVID severity and/or mortality ( n = 9) 6,11,28,33,36,38,41,43,44 ; (iv) HLA typing in wet lab was opted for the patient group but reference group were selected from the population with known HLA type through donor registry and after that association with COVID susceptibility, severity or mortality were analyzed ( n = 6) 5,24,26,32,34,45 ; (v) in this approach, metagenomics data from patients were used to predict HLA type using HLA prediction software (HLAminer, OptiType, Seq2HLA, etc.) with or without control group ( n = 4) 1,23,35,40 ; (vi) lastly, two studies observed human monocyte HLA‐DR (mHLA‐DR) expression among healthy people and different clinical stages of COVID patients to identify any impact of altered mHLA‐DR expression with COVID‐19 prognosis ( n = 2) 37,39 (Tables 1 and 2).…”

“…Six types of approaches were observed when it came to data sourcing for analysis, including both dry lab and wet lab, which are briefly discussed here-(i) HLA typing for both patient and control group were carried out in wet 6,11,28,33,36,38,41,43,44 ; (iv) HLA typing in wet lab was opted for the patient group but reference group were selected from the population with known HLA type through donor registry and after that association with COVID susceptibility, severity or mortality were analyzed (n = 6) 5,24,26,32,34,45 ; (v) in this approach, metagenomics data from patients were used to predict HLA type using HLA prediction software (HLAminer, OptiType, Seq2HLA, etc.) with or without control group (n = 4) 1,23,35,40 ; (vi) lastly, two studies observed human monocyte HLA-DR (mHLA-DR) expression among healthy people and different clinical stages of COVID patients to identify any impact of altered mHLA-DR expression with COVID-19 prognosis (n = 2) 37,39 (Tables 1 and 2).…”

“…Among 36 studies, seven explored the outcome related to only COVID susceptibility 17,20,22,26,31,35,36 ; 14 studies investigated only severity 1,2,5,18,19,24,27,29,32,37,39,40,42,43 and four studies observed association with only mortality. 6,11,13,25 The association of HLA alleles with either susceptibility and mortality of COVID-19 12,28,33,34,38 or susceptibility and severity of COVID-19 14,23,41,44,45 were explored by five studies, respectively and only one study explored HLA association with COVID severity and mortality. 21 Among 117 significantly altered alleles, 85 (72.65%) alleles were found to have a harmful effect or positive 2).…”