Understanding the genetic determinant of severity in viral diseases: a case of SARS-Cov-2 infection

Abstract

Background: Numerous research studies have identified specific human gene variants that affect enhanced susceptibility to viral infections. More recently is the current pandemic where the SARS-CoV-2 infection has shown a high degree of person-to-person clinical variability. A wide range of disease severity occurs in the patients' experiences, from asymptomatic cases, mild infections to serious life threatening conditions requiring admission into the intensive care unit (ICU).

Main body of the abstract: Although, it is generally reported that age and co-morbidities contribute significantly to the variations in the clinical outcome of the scourge of COVID-19, a hypothetical question of the possibility of genetic involvement in the susceptibility and severity of the disease arose when some unique severe outcomes were seen among young patients with no co-morbidity. The role human genetics play in clinical response to the viral infections is scarcely understood; however, several ongoing researches all around the world are currently focusing on possible genetic factors. This review reports the possible genetic factors that have been widely studied in defining the severity of viral infections using SARS-CoV-2 as a case study. These involve the possible involvements of ACE2, HLA, and TLR genes such as TLR7 and TLR3 in the presentation of a more severe condition.

Short conclusion: Understanding these variations could help to inform efforts to identify people at increased risk of infection outbreaks through genetic diagnosis of infections by locating disease genes or mutations that predispose patients to severe infection. This will also suggest specific targets for therapy and prophylaxis.

Keywords: Angiotensin-converting enzyme 2 (ACE2) gene; COVID-19; Coronavirus; Human leucocyte antigen (HLA) allele; SARS-CoV-2; Toll-like receptor (TLR).

Fig. 1

Schematic view of the gene locus of TLR7 and its more similar homolog TLR8 together with the ACE2 gene all present at the Xp22 region on the human X chromosome

Fig. 2

Schematic view of the HLA gene locus on the human chromosome 6, showing classical HLA class I (most common are HLA-A, HLA-B, and HLA-C) and class II (DR, DQ, DP, and DM) molecules in relation to other immune response gene found on the class III region