**1. Introduction**

At the time this chapter is being written, the world is still experiencing the Severe Acute Respiratory Syndrome Coronavirus −2 (SARS-CoV-2)/COVID-19 pandemic. The dominant circulating strain of the virus has gone under multiple changes during the pandemic. The initial ancestral strain gave way to the alpha strain which gave way to the delta and omicron strain, which are currently the dominating circulating strains [1]. In addition, there have been emergence of other variants of interests (VOIs) or variants of concern (VOC) such as beta, gamma, P1, P2, lambda, and mu which could be a threat to international health security [1].

The emergence of these variants suggests virus adaptations to various determinants, responsible for the selection of these mutated variants.

This perspective chapter considers different biological determinants capable to contribute to viral mutations and thereby, emergence of new variants and the potential impact of this on the tools (vaccines and antibody therapy) against the SARS-CoV-2. However, it is important to note the determinants mentioned here may not be an exhaustive list of potential mechanisms to induce mutations. This chapter is based on theoretical and fundamental scientific concepts known to be involved from past outbreaks or current case reports from the ongoing pandemic. It is known that biological and environmental, among other determinants may drive viral mutations by different processes or mechanisms. Furthermore, by considering the roles these potential determinants may or already contribute to future SARS-CoV-2 variants we can improve global pandemic responses, saves lives, and contribute to the international health security.
