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.