Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature

Filippo Migliorini,Markus Tingart,Nicola Maffulli,Francesco Oliva,Filippo Spiezia,Ernesto Torsiello

doi:10.1186/s40001-021-00563-1

Abstract

The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis and related clinical consequences have not yet been elucidated. Infection rates, as well morbidity and mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence the outcome of the condition, to clarify which aspects could be related the clinical variability of SARS-CoV-2 disease. We reviewed the studies exploring the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression, discussing also the contribution of the immunological patterns MHC-related. In March 2021, the main online databases were accessed. All the articles that investigated the possible association between the HLA genotypes and related polymorphisms with susceptibility, severity and progression of COVID-19 were considered. Although both genetic and environmental factors are certainly expected to influence the susceptibility to or protection of individuals, the HLA and related polymorphisms can influence susceptibility, progression and severity of SARS-CoV-2 infection. The crucial role played by HLA molecules in the immune response, especially through pathogen-derived peptide presentation, and the huge molecular variability of HLA alleles in the human populations could be responsible for the different rates of infection and the different patients following COVID-19 infection.

Highlights

In December 2019 a cluster of pneumonia cases caused by an unknown etiological agent broke out in Wuhan [1]
The following keywords were used in combination: coronavirus, Coronavirus disease (COVID)-19, severe acute respiratory syndrome (SARS)-CoV-2, SARS-CoV-1, middle east respiratory syndrome (MERS), infection, susceptibility, severity, progression, Human Leukocyte Antigens (HLA), major histocompatibility complexes (MHC), haplotypes, genotypes, locus, genes, alleles, polymorphisms, frequency, antigens, epitope, peptide, binder, factors, outcome, affinity, T cells, B cells, natural killer (NK) cells, lymphocyte, antibodies, association, correlation, genetic, pathogenesis, disease, immunology, virus, system, humoral, cellular, response, adaptive, interaction, epidemic, role, manifestation, clearance, risk, cytokines, dysregulation, affinity, clinic, injury, prognosis, diagnosis, therapy, variability, distribution, inflammatory, reaction, mortality, morbidity
Based on the experience gained during the previous severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics, it is likely that both innate and adaptive host immunity play a role in viral clearance, disease severity and the different clinical manifestations of the disease [49–52]

Summary

Background

In December 2019 a cluster of pneumonia cases caused by an unknown etiological agent broke out in Wuhan [1]. Considering the current situation, it would be useful to identify diagnostic and therapeutic targets, Migliorini et al Eur J Med Res (2021) 26:84 as well reliable predictors, to counter this pandemic In this context, the role of the Human Leukocyte Antigens (HLA) complex appears interesting, since its genetic variability is directly associated with individual variations in the immune response against pathogens and susceptibility to infectious diseases [7]. HLA locus The human leukocyte antigen (HLA) gene complex is a locus of genes present on chromosome 6 that encodes proteins known ad major histocompatibility complexes (MHC) They constitute a specific group of molecules expressed on the cell surface, crucial for the recognition of non-self-molecules by the acquired immune system [44]. The HLA alleles are variable and polymorphic, and individuals with different HLA genotypes may trigger different immune responses against pathogens [47, 48]

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