COVID-19: The Ethno-Geographic Perspective of Differential Immunity

Abstract

Coronavirus disease 2019 (COVID-19), the agent behind the worst global pandemic of the 21st century (COVID-19), is primarily a respiratory-disease-causing virus called SARS-CoV-2 that is responsible for millions of new cases (incidence) and deaths (mortalities) worldwide. Many factors have played a role in the differential morbidity and mortality experienced by nations and ethnicities against SARS-CoV-2, such as the quality of primary medical health facilities or enabling economies. At the same time, the most important variable, i.e., the subsequent ability of individuals to be immunologically sensitive or resistant to the infection, has not been properly discussed before. Despite having excellent medical facilities, an astounding issue arose when some developed countries experienced higher morbidity and mortality compared with their relatively underdeveloped counterparts. Hence, this investigative review attempts to analyze the issue from an angle of previously undiscussed genetic, epigenetic, and molecular immune resistance mechanisms in correlation with the pathophysiology of SARS-CoV-2 and varied ethnicity-based immunological responses against it. The biological factors discussed here include the overall landscape of human microbiota, endogenous retroviral genes spliced into the human genome, and copy number variation, and how they could modulate the innate and adaptive immune systems that put a certain ethnic genetic architecture at a higher risk of SARS-CoV-2 infection than others. Considering an array of these factors in their entirety may help explain the geographic disparity of disease incidence, severity, and subsequent mortality associated with the disease while at the same time encouraging scientists to design new experimental approaches to investigation.

Keywords: COVID-19; copy number variation (CNV); endoretroviral genome (ERV); geographic disparity; microbiome; virome.

Figure 1

This figure is an illustration of the human microbiome, specifically the human virome and its few functions related to immunity against viral infection. (a) is an illustration that shows modulation or the positive reinforcement of the host immune system by virome molecules and particles that enhance the immune system’s ability to fight the incoming infection. (b) is a diagram illustrating the competition that is given to the incoming viral particles by the host virome, which essentially protects the host cells from infection as the virome particles act as guards of the region. (c) shows the production of IL, interferon, MHC molecules, all of which are essential parts of the host immune system, and their production with the help of virome demonstrates their role in the proper functioning of the host’s immune system.

Figure 2

This illustrates some of the functions that HERV genome plays in protecting the human body against external viral infection. (a) shows the production of viral proteins by the HERV genome that are complimentary to the external virus in a negative way, thus affecting their success. (b) is an illustration showing the interference produced by HERV proteins that result in inhibiting or blocking the viral replication cycle. (c) is an illustration showing the phenomenon of receptor interference that involved the blockage of the site of entry for the foreign virus by HERV proteins, thus resulting in the prevention of viral infection of the cell. (d) is an illustration that shows the production of long non-coding RNA sequences that help in the modulation of the host antiviral immune system.

Figure 3

A stepwise (1–15) illustration of how HERVs can induce innate and adaptive immunity through the production of retroviral proteins that activate B and T cells to either produce anti-HERV antibodies or immune proteins IL-1β, Il-6, IL-12p40, and TNF-α to protect against newer, more evolved strains of viral pathogens.

Figure 4

This is a diagrammatic representation of the relationship between gene dosage and gene expression in three individuals. The diagram is an example of the copy number variation phenomenon showing us the variable copy numbers of a gene in different people. The protein production is observed as (a) high in person 1, (b) moderate in 2 as compared to (c) low in person 3 due to the variable number of gene copies.