**1. Introduction**

In the current COVID-19 pandemic context, with a count of 544 million cases including 6.33 million deaths [1], a worldwide collective effort for observing the SARS-CoV-2 genomic landscape, monitoring the virus mutational rate and the emergence of new variants is noted. As a result of SARS-CoV-2 genome modification, the virus may gain selective advantage regarding transmission and virulence, increase disease severity and eventually, significantly impact public health either by affecting the current vaccine performance or interfering with the current diagnostic and therapeutic strategies [2].

A series of measures have been taken globally for optimal management of the emergence of SARS-CoV-2 variants. World Health Organization (WHO), international health expert networks, and researchers have continuously been monitoring virus evolution by examining the mutations occurring in the SARS-CoV-2 genome.

During an emergency situation in a health care system, the most important actions are the rapid and effective identification of pathogen and epidemiological surveillance to allow disease control reaction. The development of next-generation sequencing (NGS) techniques has led to an enormous amount of genomic sequence data [3]. In COVID-19 genomic era, the accumulation of this considerable amount of genomic data shared in international repositories, such as GISAID EpiCOV, COG-UK, or NCBI, allowed the evaluation of the transmission pattern of viral strains, the impact of each variant, and also the comparison between the available vaccines and the circulating viral variants [4] and it also oriented global public health measures.

At present, two and a half years after the beginning of the pandemic, we can say that given the mutations and recombination of the viral genes, we are facing a different type of SARS-CoV-2 than the one that emerged in China in December 2019. On November 26, 2021, Omicron, B.1.1.529 Pango lineage has emerged, and currently, it represents the circulating variant of concern, still threatening several countries with its sub-lineages.

In this chapter, we summarize the genomic medicine impact on the identification of the new infectious agent that causes COVID-19, on development of molecular tests for diagnostic and surveillance of the emergent variants, describe their importance in managing transmission, preventing failure of diagnostic tests, on sustaining effectiveness of vaccines and therapeutics and eventually, to inform the public health policies.
