The role of HLA genotypes in understanding the pathogenesis of severe COVID-19

Abstract

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has caused human tragedy through the global spread of the viral pathogen SARS-CoV-2. Although the underlying factors for the severity of COVID-19 in different people are still unknown, several gene variants can be used as predictors of disease severity, particularly variations in viral receptor genes such as angiotensin-converting enzyme 2 (ACE2) or major histocompatibility complex (MHC) genes. The reaction of the immune system, as the most important defense strategy in the case of viruses, plays a decisive role. The innate immune system is important both as a primary line of defense and as a trigger of the acquired immune response. The HLA-mediated acquired immune response is linked to the acquired immune system. In various diseases, it has been shown that genetic alterations in components of the immune system can play a crucial role in how the body responds to pathogens, especially viruses. One of the most important host genetic factors is the human leukocyte antigen (HLA) profile, which includes HLA classes I and II and may be symbolic of the diversity of immune response and genetic predisposition in disease progression. COVID-19 will have direct contact with the acquired immune system as an intracellular pathogen after exposure to the proteasome and its components through class I HLA. Therefore, it is assumed that in different genotypes of the HLA-I class, an undesirable supply causes an insufficient activation of the immune system. Insufficient binding of antigen delivered by class I HLA to host lymphocytes results in uncertain identification and insufficient activation of the acquired immune system. The absence of secretion of immune cytokines such as interferons, which play an important role in controlling viral infection in the early stages, is a complication of this event. Understanding the allelic diversity of HLA in people infected with coronavirus compared with uninfected people of one race not only allows identification of people with HLA susceptible to COVID-19 but also provides better insight into the behavior of the virus, which helps to take effective preventive and curative measures earlier.