SARS-CoV-2 Variants of Concern: Biological Implications of Immunogenicity and Comorbidity
type: CreativeWork
description: When coronavirus disease 2019 (COVID-19) emerged in human populations in late 2019, there was nothing known about the virus, SARS-CoV-2, besides that it had a high degree of similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). The prior published research on these viruses set a strong foundation for the research approaches needed to quickly stand-up medical countermeasures for treatment of COVID-19. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) soon revealed a high propensity to evolve new variants that could engage host cell receptors with greater affinity and escape host immunity. With each wave of new variants of concern (VOC), scientists unveiled new mutations that granted each virus the ability to reinfect and cause disease, resulting in nearly three years of global COVID-19 infection and hospitalization that continues to this day. The pandemic created an urgent and immediate need for the development of a wide variety of in vivo and in vitro models of SARS-CoV-2 which could define the unique phenotypes of each variant so that medical countermeasures could be developed. Hence my thesis, conducted during the peak of the pandemic and after focused on two main scientific contributions toward characterizing SARS-CoV-2 in vitro and in vivo. My first research efforts sought to understand the immunity and protection conferred by challenge with an early stain of SARS-CoV-2 called Washington (or WA1) based on its origin to the later variant of concern (VOC), Alpha and Delta in a lethal mouse model. The transgenic mouse model was genetically modified to express the primary receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). As the infection of the K18 hACE2 mouse model with SARS-CoV-2 results in lethality, a dose needed to be chosen that the mouse survives in order to examine protection conferred by an initial infection. The mice that survived the SARS-CoV-2…
abstract: When coronavirus disease 2019 (COVID-19) emerged in human populations in late 2019, there was nothing known about the virus, SARS-CoV-2, besides that it had a high degree of similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). The prior published research on these viruses set a strong foundation for the research approaches needed to quickly stand-up medical countermeasures for treatment of COVID-19. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) soon revealed a high propensity to evolve new variants that could engage host cell receptors with greater affinity and escape host immunity. With each wave of new variants of concern (VOC), scientists unveiled new mutations that granted each virus the ability to reinfect and cause disease, resulting in nearly three years of global COVID-19 infection and hospitalization that continues to this day. The pandemic created an urgent and immediate need for the development of a wide variety of in vivo and in vitro models of SARS-CoV-2 which could define the unique phenotypes of each variant so that medical countermeasures could be developed. Hence my thesis, conducted during the peak of the pandemic and after focused on two main scientific contributions toward characterizing SARS-CoV-2 in vitro and in vivo. My first research efforts sought to understand the immunity and protection conferred by challenge with an early stain of SARS-CoV-2 called Washington (or WA1) based on its origin to the later variant of concern (VOC), Alpha and Delta in a lethal mouse model. The transgenic mouse model was genetically modified to express the primary receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). As the infection of the K18 hACE2 mouse model with SARS-CoV-2 results in lethality, a dose needed to be chosen that the mouse survives in order to examine protection conferred by an initial infection. The mice that survived the SARS-CoV-2…
author: Nichols, Jacob
keywords: coronavirus, diabetes, sars-cov-2, variants, Life Sciences, Microbiology, Virology
date published: 2025-01-01T08:00:00Z
date modified: 2026-07-24T05:00:53Z
provider: University of Tennessee Health Science Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Tennessee Health Science Center