Will a little change do you good? A putative role of polymorphisms in COVID-19

Abstract

An alarming disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 has emerged as an unprecedented public health problem and ignited a world health crisis. As opposed to what was believed at the beginning of the pandemic, the virus has not only spread but persevere causing secondary waves and challenging the concept of herd immunity against viral infections. While the majority of SARS-CoV-2-infected individuals may remain asymptomatic, a fraction of individuals may develop low to high-grade severity signs and symptoms of COVID-19. The disease is multifactorial and can progress quickly, leading to severe complications and even death in a few days. Therefore, understanding the pre-existing factors for disease development has never been so pressing. In this scenario, the insights on the mechanisms underlying disease allied to the immune response developed during the viral invasion could shed light on novel predictive factors and prognostic tools for COVID-19 management and interventions. A recent genome-wide association study (GWAS) revealed several molecules that significantly impacted critically ill COVID-19 patients, leading to the core mechanisms of Covid-19 pathogenesis. Considering these findings and the fact that ACE-2 polymorphisms alone cannot explain disease progress and severity, this review aims at summarizing the most important and recent findings of the research and expert consensus of possible cytokine-related polymorphisms existing in the differential expression of paramount immune molecules that could be crucial for providing guidelines for decision-making and appropriate clinical management of COVID-19.

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients

“…Therefore, although promising, these two mediators should be considered carefully as targets for COVID-19 therapy with anti-IL-6 and anti-TNF monoclonal antibodies. Regarding the Interferon pathway, specific polymorphisms in genes related to cytokines are strongly associated with disease outcome, such as Interferon related genes (34,35). Recent investigations have shown that a worst COVID-19 outcome is closely associated to polymorphisms in genes related to the production of proinflammatory IFN-g and IL-12 (25).…”

“…In fact, our results show lower levels of IFN-g in the airway of critically ill COVID-19 patients that progress to death, which suggests the protective role of this cytokine against SARS-CoV-2 infection. In addition, high expression of IFNAR2 interferon receptor subunit reduced the chances of severe COVID-19, indicating that the proinflammatory profile of cytokines are important to disease outcome in COVID-19 (34,35). In fact, lower levels of circulating IFN-g were associated to a higher risk of lung fibrosis in COVID-19 patients (36).…”

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

“…IL1 RN (rs315952—T/C) and IL4 (rs2070874—C/T/ IL4 + 1059 C/T) SNPs have been associated with COVID‐19 severity. 55 , 56 The SNPs in the IL6 gene have been associated with pneumonia and COPD and also certain viral infections such as hepatitis B virus, hepatitis C virus (HCV), and influenza virus. 57 , 58 , 59 Low rate of IL6 CC (rs1800795) SNP was related to the persistence of HCV infection.…”

Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

“…The different expression of cytokines caused by point mutations in these genes interferes in the evolution of the immune response and in the different clinical outcomes of COVID-19. These polymorphisms can also affect the response to the use of therapies and vaccines [164].…”