**5. Conclusion**

This chapter presents theoretical and current determinants for variant emergence, specifically for SAR-CoV-2. The emergence of different VOC through the evolutionary cycle of the SARS-CoV-2 virus during the current pandemic (2019 ongoing) makes it important to understand the biological determinants of new emerging variants. The inherent errors in viral replication in humans and animal reservoirs combined with immunological selective pressure result in the Darwinian selection of variants of SARS-CoV-2 with potential for higher transmissibility and resistance to vaccine-based immunity or monoclonal antibodies. The different types of vaccines and associated immune response, partial immunization, waning of immunity, and heterogenicity in worldwide immunity results in wide differences in immunological selective pressure based on regions and virus evolutions. The global inequality in vaccine distribution further complicates this immunological selection pressure. The epidemiological and evolutionary cycle can result in viral adaptations with potential for selection of variants with higher transmissibility and immune escape properties. The emergence of these dangerous new variants can influence vaccine and antibody therapy effectiveness necessitating modifications in antigenic sequences used in production. This emergence of novel variants thus is a concern for international health security with a potential for furthering the COVID-19 pandemic and its associated negative health, economic, and social effects.
