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.

Hypotheses and facts for genetic factors related to severe COVID-19

“…Owing to the fact that the ACE2 gene is located on the X chromosome, it has been suggested that the higher mortality rate among males should possibly be related to its lower expression. Furthermore, estrogen increases the ACE2 expression and activity in women[ 63 , 64 ]. Renin-angiotensin system balance is maintained by the ACE and ACE2 function; thus, ACE2 gene variants or their overexpression lead to renin-angiotensin system imbalance resulting in vasoconstriction, hypercoagulation, fibrosis, alveolar cell apoptosis, increased ROS production, and lung damage overall.…”

“…Allele frequency variations of the ACE2 gene in different populations might be due to SNPs. Compared to a global average, the protective variants were found to be of higher frequency in the Asian population, whereas the risk variants were more frequent among the population of European descent[ 10 , 63 ].…”

Routine Hematological Parameters May Be Predictors of COVID-19 Severity

“…The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the Coronavirus disease 2019 (COVID-19), has affected over 100 million globally with over 2.5 million fatalities to date leading to a global pandemic of unprecedented size (1). COVID-19 symptoms can vary from person to person, leading to a clinical manifestation of disease ranging from asymptomatic to mild infections, through to serious, lifethreatening cases requiring admission to the intensive care unit (ICU) (2,3). The severity of COVID-19 depends on several factors including age, gender, and the presence of existing comorbidities such as diabetes, hypertension, or respiratory disease (4-6); however, it is difficult to predict the future severity of COVID-19 infection at the time of the patients' admission to the hospital.…”

“…Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland, 2 School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland, 3 To date, coronavirus disease 2019 (COVID-19) has affected over 100 million people globally. COVID-19 can present with a variety of different symptoms leading to manifestation of disease ranging from mild cases to a life-threatening condition requiring critical care-level support.…”

Evaluation of hematological parameters in covid-19 patients in district Hapur

“…The COVID-19 is a high contagious disease and spread around the globe within a short time, and the world health organization (WHO) has declared it a pandemic on March 12, 2020 [3] . COVID-19 symptoms can vary from person to person, leading to a clinical manifestation of disease ranging from asymptomatic to mild infections, through to serious, life threatening cases requiring admission to the intensive care unit (ICU) [4,5] . The severity of COVID-19 depends on several factors including age, gender, and the presence of existing comorbidities such as diabetes, hypertension, or respiratory disease [6][7][8] ; however, it is difficult to predict the future severity of COVID-19 infection at the time of the patients' admission to the hospital.…”