PhD defence A.Z. (Anna) Mykytyn

Brief summary:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan in December 2019 and is the causative agent of the COVID-19 pandemic. SARSCoV-2 continues to be a public health burden, causing thousands of new infections and hundreds of deaths daily. When SARS-CoV-2 first emerged, it was critical to understand its pathogenic potential and to develop effective treatments and vaccines. Now the virus continues to circulate and evolve, leading to the emergence of new variants. Therefore, our pool of knowledge about the pathogenesis of emerging variants and the efficacy of our existing treatments needs to be regularly updated.

• Part I of this thesis, the entry mechanisms of SARS-CoV-2 were studied using relevant primary cell systems.
• Part II of this thesis focused on the antigenic evolution of SARS-CoV-2.
• Part III of this thesis focused on the combined antigenic and replicative fitness evolution of SARS-CoV-2.

This thesis demonstrates the multiple ways SARS-CoV-2 is evolving. It is critical to phenotype newly emerging variants to determine changes in their pathogenicity, transmissibility and immune evasive properties. By combining the tools described in this thesis with full genome sequencing, future research may be able to predict the phenotype of newly emerging variants from the genome alone. However, appropriate cell systems and data interpretation are critical before this would be possible.