The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

• Published in: Journal of clinical laboratory analysis 2024-01, Vol.38 (1-2), p.e25005-n/a
• Main Authors: Hoseinnezhad, Taraneh, Soltani, Nasrin, Ziarati, Sarina, Behboudi, Emad, Mousavi, Mohammad Javad
• Format: Article
• Language: English
• Subjects: Alleles; Antigens; COVID-19; COVID-19 - genetics; COVID-19 vaccines; disease outcomes; Disease transmission; ethnicity; Gene frequency; Gene Frequency - genetics; Genetic diversity; genetic variation; Histocompatibility antigen HLA; HLA alleles; Humans; Immune system; Lymphocytes; Mortality; Pandemics; Peptides; Polymorphism; Population genetics; Proteins; Review; SARS-CoV-2 - genetics; SARS‐CoV‐2; Severe acute respiratory syndrome coronavirus 2; severity; Signal transduction; susceptibility; Therapeutic applications; Viruses
• ISSN: 0887-8013; 1098-2825; 1098-2825
• DOI: 10.1002/jcla.25005

Background The COVID‐19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID‐19 outcomes. Methods In this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID‐19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID‐19 incidence and severity. Results Our review provides insights into the immunological mechanisms involving HLA‐mediated responses to COVID‐19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA‐A02, may confer a lower risk of COVID‐19, while others, like HLA‐C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations. Conclusion Considering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID‐19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants. This figure presents a worldwide vision illustrating the relationship between the frequencies of HLA‐C04 and HLA‐A02 alleles and their respective associations with COVID‐19 susceptibility and mortality rates across different regions. The darker shaded areas represent regions with moderate‐to‐high frequencies of selected alleles and higher rates of susceptibility and mortality from COVID‐19. However, there are exceptions, such as China, where despite a higher frequency of HLA‐C04, lower incidence and mortality rates are observed. This suggests the influence of factors beyond host genetics, including government policies (e.g., Zero‐COVID‐19 policy), timely implementation of quarantine measures, access to vaccines and treatments, and well‐equipped medical facilities. Similarly, the figure highlights the protective effe