Since its emersion, coronavirus disease 2019 (COVID‐19) has been a significant global dilemma. Several mutations in the severe acute respiratory virus (SARS‐Co‐2) genome has given rise to different variants with various levels of transmissibility, severity and mortality. Up until November 2021, the variants of concern declared by the World Health Organization were Alpha, Beta, Delta and Gamma. Since then, a novel variant named Omicron (B.1.1.529) has been developed. BA.1, BA.1.1, BA.2 and BA.3 are four known subvariants of Omicron. The Omicron variant involves new mutations in its spike protein, most of which are in its receptor binding site, and increase its transmissibility and decrease its antibody and vaccine response. Understanding the virology and mutations of Omicron is necessary for developing diagnostic and therapeutic methods. Moreover, important issues, such as the risk of re‐infection, the response to different kinds of vaccines, the need for a booster vaccine dose and the increased risk of Omicron infection in pediatrics, need to be addressed. In this article, we provide an overview of the biological and immunopathological properties of Omicron and its subvariants, its clinical signs and symptoms, Omicron and pediatrics, vaccines against Omicron, re‐infection with Omicron, diagnostic approaches and specific challenges of Omicron in the successful control and management of the rapid global spread of this variant.

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