**Abstract**

In epidemic and pandemic circumstances, mutant RNA viruses go into a Darwinian selection of species with the predominance of the most transmissible, pathogenic, and virulent variants. Nevertheless, our current knowledge about the determinants of emergence of the new mutants is limited. The perspective chapter presents theoretical concepts related to biological determinants responsible for viral mutations or potential variant emergence. A scoping literature review was done in biomedical databases (PubMed, Medline) and google search engine with papers selected based about the book chapter. Public health and governmental agency websites were utilized for most recent information. Molecular determinants, the heterogenic herd immunity achieved by world populations, partial induced natural immunity by the disease, partial artificial immunity caused by incomplete immunization schedules, animal reservoirs, immunosuppression and chemical and biological antiviral therapies can result in genomic mutations combined with immunological selective pressure resulting in emergence of variants of concern. These variants could be resistant to current vaccines and monoclonal antibodies and can influence the future directions of the COVID-19 pandemic. This can be a threat to international health security and thus it is important to increase the genomic surveillance for mutations and research into modified vaccines and monoclonal antibodies against newer antigens to prevent the prolongation of the pandemic.

**Keywords:** SARS-CoV-2, COVID-19, variants, determinants
