Project 467019

Like other viruses, SARS-CoV-2, the virus that causes COVID-19, constantly changes via mutation. Throughout the global pandemic, several variants of concern (VOCs) have been identified. A variant is of concern if it (1) spreads more easily, (2) is associated with increased disease severity, or (3) has the ability to resist the immune system or therapeutics. The biological properties of VOCs are poorly understood. Furthermore, several studies have shown that males are at a higher risk of severe COVID-19 infection, in comparison to females. Immune system and hormonal analyses have been conducted in an effort to explain this sex-based difference in COVID-19 disease severity. However, the biological properties of the virus have yet to be analyzed. The purpose of this study is to identify biological differences between SARS-CoV-2 VOCs and to determine if the increased severity of these variants is attributed to certain biological properties. To do so, I will infect human airway epithelial cells and three-dimensional (3D) human cell-based lung models with human coronavirus 229E (hCoV-229E) as well as four variants of concern. Following infection, I will extract, purify, and sequence the RNA from the infected cells. The sequencing results will be used to analyze cellular signaling pathways that are altered upon VOC infection. The 3D lung models will be derived from both male and female donors of the same age, leading me to be able to determine what factors may contribute to the sex-based difference in disease severity. The results of this study will help in better understanding the biological properties of VOCs and could be used to develop drugs against emerging variants.