The epidemiological surveillance efforts for the pandemic thus far have been instrumental in the timely discovery and tracking of new variants, a true public health necessity. However, there is valuable information tucked away in the variants that have come and gone during the past two years. Those minor variants that caused local surges, but never got a foothold globally, are powerful tools to help elucidate the transmission and diversity of SARS-CoV-2 variants. In this proposal, we aim to use SARS-CoV-2 variants of the past to better understand parts of the pandemic by investigating their transmissibility and infectious properties. A better understanding of the infectivity differences between variants will allow the field to further understand transmissibility. This ultimately carries over into disease prevention and all the associated post-infection complications, many of which are cardiac in nature. The overall hypothesis of this proposal is that variants which had success globally cluster together and have properties that permitted them to dominate over lesser variants and wild-type (WT) SARS-CoV-2. We will elucidate the mechanisms by which these fitness advantages occur by characterizing viral kinetics (growth curves, competition assays), temperature sensitivity and cell-type specific infectivity. This work will be performed in an upper and lower respiratory air-liquid-interface systems to best recapitulate an in vivo system. This research will be conducted under the mentorship of my mentor, Dr. Emily Bruce and co-mentor, Dr. Dimitry Krementsov, in addition to my thesis committee. Dr. Emily Bruce, Dr. Dimitry Krementsov, and I have created an Individual Development Plant (IDP) which involves me presenting ongoing work at conferences and internal meetings, collaborations, and strategies to help me master new techniques. Within the University of Vermont, this work will be conducted within a collaborative laboratory environment and supported by peers and investigators throughout the Microbiology & Molecular Genetics department through frequent presentations of ongoing work.