HLA, Immune Response, and Susceptibility to COVID-19

Abstract

The severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) that appeared in December 2019 has precipitated the global pandemic Coronavirus Disease 2019 (COVID-19). However, in many parts of Africa fewer than expected cases of COVID-19, with lower rates of mortality, have been reported. Individual human leukocyte antigen (HLA) alleles can affect both the susceptibility and the severity of viral infections. In the case of COVID-19 such an analysis may contribute to identifying individuals at higher risk of the disease and the epidemiological level to understanding the differences between countries in the epidemic patterns. It is also recognized that first antigen exposure influences the consequence of subsequent exposure. We thus propose a theory incorporating HLA antigens, the "original antigenic sin (OAS)" effect, and presentation of viral peptides which could explain with differential susceptibility or resistance to SARS-CoV-2 infections.

Keywords: Coronavirus Disease 2019; human leukocyte antigens; immune response; original antigenic sin; vaccine design.

Figure 1

In the optimal immune response (on the left) against SARS-CoV-2 and its antigenic variants, the particular adaptive immunity is often associated with (color matching) the symbolic antibody and the spike proteins that cover the outer surface of the virion; Original antigenic sin explains the propensity of the immune response to use immunological memory that relies on the previous infection when a new slightly altered strain of the foreign pathogen is identified. As we see in the OAS model (right), the particular adaptive immune response is only installed against the original virus and is not used to combat the mutated forms of the virus, leading to a less specific and less efficient maladaptive response (Created in BioRender.com) (8).