A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Abstract

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all the previously emerged variants. The numerous mutations in Omicron's viral genome and its sub-lineages attribute it a larger amount of viral fitness, owing to the alteration of the transmission and pathophysiology of the virus. With a rapid change to the viral structure, Omicron and its sub-variants, namely BA.1, BA.2, BA.3, BA.4, and BA.5, dominate the community with an ability to escape the neutralization efficiency induced by prior vaccination or infections. Similarly, several recombinant sub-variants of Omicron, namely XBB, XBD, and XBF, etc., have emerged, which a better understanding. This review mainly entails the changes to Omicron and its sub-lineages due to it having a higher number of mutations. The binding affinity, cellular entry, disease severity, infection rates, and most importantly, the immune evading potential of them are discussed in this review. A comparative analysis of the Delta variant and the other dominating variants that evolved before Omicron gives the readers an in-depth understanding of the landscape of Omicron's transmission and infection. Furthermore, this review discusses the range of neutralization abilities possessed by several approved antiviral therapeutic molecules and neutralizing antibodies which are functional against Omicron and its sub-variants. The rapid evolution of the sub-variants is causing infections, but the broader aspect of their transmission and neutralization has not been explored. Thus, the scientific community should adopt an elucidative approach to obtain a clear idea about the recently emerged sub-variants, including the recombinant variants, so that effective neutralization with vaccines and drugs can be achieved. This, in turn, will lead to a drop in the number of cases and, finally, an end to the pandemic.

Keywords: Omicron: sub-lineages; disease severity; transmission and infection.

Figure 1

A timeline describes the origin of SARS-CoV-2 Omicron and different times of origin of Omicron’s sub-variants.

Figure 2

The new wave generated due to high infection worldwide due to Omicron’s infection. The new wave is called the Omicron wave. The peak of the Omicron wave is very high compared to the other waves, such as the Alpha wave and the Beta wave, etc.

Figure 3

The figure illustrates different sub-variants of Omicron and their significant mutations in S-glycoprotein. (A) The figure describes different sub-variants of Omicron and their features. It describes the features of BA.1, BA.2, BA.3, BA.4, and BA.5. (B) The figure illustrates different mutations in S-glycoprotein of different sub-variants of Omicron. It describes the S-glycoprotein mutations of BA.1, BA.2, BA.3, BA.4, and BA.5.

Figure 3

The figure illustrates different sub-variants of Omicron and their significant mutations in S-glycoprotein. (A) The figure describes different sub-variants of Omicron and their features. It describes the features of BA.1, BA.2, BA.3, BA.4, and BA.5. (B) The figure illustrates different mutations in S-glycoprotein of different sub-variants of Omicron. It describes the S-glycoprotein mutations of BA.1, BA.2, BA.3, BA.4, and BA.5.

Figure 4

The figure shows different significant mutations in a 3D model of the S-glycoprotein of Omicron and its different sub-variants. (A) The figure shows different significant mutations in a 3D model of the S-glycoprotein of Omicron. (B) The figure shows different significant mutations in a 3D model of the S-glycoprotein of Omicron’s sub-variants, BA.1 and BA.2.

Figure 5

The figure shows viral load in the respiratory tract and the lungs during an infection with the wild strain of SARS-CoV-2 and Omicron. The figure also describes the common symptoms of Omicron-infected patients. (A) It shows high viral load in the respiratory tract during Omicron infection. It shows high viral load in lungs during an infection with the wild strain of SARS-CoV-2. (B) The figure depicting the common clinical symptoms of Omicron-infected patients.

Figure 5

The figure shows viral load in the respiratory tract and the lungs during an infection with the wild strain of SARS-CoV-2 and Omicron. The figure also describes the common symptoms of Omicron-infected patients. (A) It shows high viral load in the respiratory tract during Omicron infection. It shows high viral load in lungs during an infection with the wild strain of SARS-CoV-2. (B) The figure depicting the common clinical symptoms of Omicron-infected patients.

Figure 6

The figure shows the phylogenetic tree of the Omicron and its sub-variants. It also describes the distribution of Omicron and its sub-variants in the entire world. (A) The circular phylogenetic tree using the Omicron and its sub-variants (B) The distribution of Omicron and its sub-variants. These two figures (A,B) were developed using the next strain server.

Figure 6

The figure shows the phylogenetic tree of the Omicron and its sub-variants. It also describes the distribution of Omicron and its sub-variants in the entire world. (A) The circular phylogenetic tree using the Omicron and its sub-variants (B) The distribution of Omicron and its sub-variants. These two figures (A,B) were developed using the next strain server.

Figure 7

The figure shows the interaction structure of neutralizing antibodies (nAb) with the Omicron spike protein. It shows the interaction Fab fragment of ZCB11 against the SARS-CoV-2 Omicron spike. The structure was developed from a PDB file (PDB id: 7XH8).