COVID-19 News: Study Finds Allele HLA-A*02 Associated With Lower Risk Of Contracting COVID-19 While HLA-C*04 Increases Risk Of Severity

COVID-19 News: The global battle against the COVID-19 pandemic has been marked by a mosaic of susceptibility, severity, and mortality rates, unveiling the complex interplay between the virus and the human immune system. Amidst this complexity, researchers at Bushehr University of Medical Sciences in Iran conducted an in-depth narrative review, probing the potential role of human leukocyte antigen (HLA) genetic variants in shaping the outcomes of COVID-19. This COVID-19 News report delves into the comprehensive analysis, examining the multifaceted relationships between HLA genetic variants and COVID-19 susceptibility, severity, and mortality.


Allele HLA-A*02 Associated With Lower Risk Of Contracting COVID-19
While HLA-C*04 Increases Risk Of Severity.

Understanding the Crucial Role of HLA in Immune Response
The human leukocyte antigen (HLA) system, nestled within the intricate framework of the immune system, emerges as a linchpin in the body's ability to recognize and mount responses against foreign substances. This highly polymorphic system comprises three classes of molecules: Class I (HLA-A, HLA-B, and HLA-C), Class II (HLA-DP, HLA-DQ, and HLA-DR), and Class III, each encoding proteins vital for diverse cell functions. The orchestrated presentation of intracellular and extracellular peptides to CD8+ and CD4+ T cells respectively, sets the stage for a nuanced immune response. The HLA system, often referred to as the major histocompatibility complex (MHC), is a marvel of complexity, with its regulation playing a pivotal role in the body's immunity.
 
HLA and COVID-19 Susceptibility and Severity
SARS-CoV-2, the virus behind COVID-19, gains entry into host cells through the interaction of its glycoproteins with ACE2 and CD147 receptors. The severity of symptoms is intricately linked to the virus's ability to involve multiple organs. Understanding the factors influencing the immune response becomes paramount. White blood cells (WBCs), the foot soldiers of the immune system, traverse through the blood, lymph, lymph nodes, and spleen, encountering antigens and orchestrating responses. The interplay between HLA polymorphism and virus pathogenesis becomes significant, leading to the production of excessive cytokines and potential cell damage.
 
Allele-Specific Insights - Heroes and Villains
The review sheds light on specific HLA alleles that emerge as protagonists or antagonists in the drama of COVID-19 outcomes. HLA-A02 takes center stage as a potential protective allele, lowering the risk of contracting COVID-19. This allele, with its unique immunological fingerprint, showcases a fascinating ability to present viral peptides effectively. On the flip side, HLA-C04 emerges as a potential villain, identified as a risk allele associated with an increased likelihood of severe symptoms and mortality. The narrative review meticulously examines the nuances of these alleles, providing a nuanced understanding of their impact on COVID-19 outcomes.
 
Strong Binders and Weak Binders: Decodi ng the Affinity
The study review navigates the classification of HLA alleles into strong binders, weak binders, and non-binders based on their affinity for presenting SARS-CoV-2 peptides. HLA-A*02, with its robust binding capacity, stands out as a strong binder, showcasing high affinity for SARS-CoV-2 antigens. Conversely, HLA-C alleles, while playing a crucial role in immunity, are generally characterized as weaker binders, presenting peptides with less affinity. The geographical distribution of these alleles across populations introduces an intriguing dimension to the study, with certain regions showing a higher prevalence of strong binders.
 
HLA Distribution Worldwide and Allele Frequency Variations
The distribution of HLA haplotypes worldwide showcases significant regional variations. However, challenges arise due to the high polymorphism of the HLA molecule and its ethnic dependency. HLA typing, a costly procedure more readily available in developed countries, results in limited information on HLA allele frequencies in poorer or developing nations. The peptides' crucial role in immune responses, selectivity, and efficiency underscores the need for a nuanced understanding of these genetic factors.
 
The distribution of HLA alleles across diverse populations exhibits a tapestry of variations, intricately tied to ethnic dependencies. The highly polymorphic nature of the HLA molecule makes direct comparisons challenging, and the prevalence of HLA typing in developed countries further complicates the data landscape. To bridge this gap, new bioinformatics tools have been harnessed, aiding in predicting the affinity between peptides and HLA molecules. This, in turn, facilitates the design of peptide-based vaccines against a spectrum of viruses, including HIV-1, Ebola, and SARS-CoV-2.
 
Studies have explored the binding capabilities of various HLA classes, such as HLA-A, HLA-B, HLA-C, HLA-DQ, and HLA-DR, revealing associations with susceptibility, severity, or protective effects against COVID-19.
 
Exploring Regional Discrepancies: HLA in Global Context:
Regional variations in HLA associations with COVID-19 outcomes add layers to the complexity of this genetic dance. Analyzing HLA prevalence in different countries offers insights into how genetic diversity influences the pandemic's global landscape.
 
Egypt: Investigations into the distribution of HLA alleles among COVID-19 patients in Egypt have identified specific alleles like HLA-B51 and HLA-DRB115 linked to increased susceptibility. Conversely, HLA-A*02 has demonstrated a potential protective effect, aligning with findings in other populations.
 
Africa: The genetic diversity across the African continent introduces unique challenges in understanding HLA-COVID-19 associations. Preliminary studies suggest varied prevalence of HLA alleles in different African regions, with certain West African populations exhibiting a higher frequency of specific alleles linked to severe outcomes.HLA-B*15:03 with excellent ability to present SARS-CoV-2 peptides, appears to be recurrent in West Africa and in countries with endemic malaria was seen as protective.

China: China, as the initial COVID-19 outbreak location, has been a focal point for HLA research. Studies in different regions of China have explored HLA associations with COVID-19 severity, identifying potential risk alleles like HLA-B46 and associations with milder outcomes for HLA-C01 and HLA-A*11.
 
Japan: Investigations into HLA associations with COVID-19 outcomes in Japan reveal a distinct allele landscape. HLA-A*24 has been implicated as a potential risk allele, aligning with findings in other East Asian populations.
 
India: The vast genetic diversity in India prompts studies examining HLA-COVID-19 associations across different states. HLA-B15:03 has been identified as a potential risk allele, while HLA-A02 demonstrates a protective effect.

United Kingdom: In the United Kingdom, where the impact of COVID-19 has been substantial, research has delved into the genetic determinants of susceptibility and severity. Studies indicate that HLA-B44 may be associated with increased susceptibility, while HLA-C01 shows potential protective effects.
 
Understanding these regional HLA variations offers a roadmap for tailored public health interventions, vaccination strategies, and therapeutic approaches. The intricate dance between host genetics and viral pathogenesis unfolds differently in diverse populations, necessitating a global collaborative effort.
 
Conclusion
As the world continues to grapple with the COVID-19 pandemic, the decoding of the genetic framework involving HLA alleles provides critical insights. The global mosaic of HLA-COVID-19 associations reveals a complex interplay between genetics and viral outcomes. These findings not only contribute to our understanding of COVID-19 but also pave the way for a broader exploration of infectious disease susceptibility and severity across the globe. In the ongoing battle against the pandemic, unraveling these regional discrepancies is paramount for informed decision-making and effective public health strategies.
 
The study findings were published in the peer reviewed Journal of Clinical Laboratory Analysis.
https://onlinelibrary.wiley.com/doi/10.1002/jcla.25005
 
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https://www.thailandmedical.news/articles/covid-19-genetics