SARS-CoV-2 Omicron Variant: Epidemiological Features, Biological Characteristics, and Clinical Significance

Abstract

The SARS-CoV-2 Omicron (B.1.1529) variant was designated as a variant of concern (VOC) by the World Health Organization (WHO) on November 26, 2021. Within two months, it had replaced the Delta variant and had become the dominant circulating variant around the world. The Omicron variant possesses an unprecedented number of mutations, especially in the spike protein, which may be influencing its biological and clinical aspects. Preliminary studies have suggested that increased transmissibility and the reduced protective effects of neutralizing antibodies have contributed to the rapid spread of this variant, posing a significant challenge to control the coronavirus disease 2019 (COVID-19) pandemic. There is, however, a silver lining for this wave of the Omicron variant. A lower risk of hospitalization and mortality has been observed in prevailing countries. Booster vaccination also has ameliorated a significant reduction in neutralization. Antiviral drugs are minimally influenced. Moreover, the functions of Fc-mediated and T-cell immunity have been retained to a great extent, both of which play a key role in preventing severe disease.

Keywords: COVID-19; SARS-CoV-2 variants; mutations; neutralizing antibodies; sublineages; vaccines.

Figure 1

Spike mutations in the Omicron variant. Cartoon representation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (PDB: 7CWU_A). Red spheres represent the mutations found in the Omicron variant. The receptor binding domain (RBD) and amino terminal domain (NTD) are shown in blue and purple, respectively. The mutations are marked according to the immune escape (green) and increased infectivity (yellow).

Figure 2

RBD mutations in the Omicron variant. Surface representation of the receptor-binding domain (RBD) in complex with the angiotensin-converting enzyme 2 (ACE2) (PDB: 7A94) (A). Surface representation of the RBD mutations (PDB: 7A94) in three orientations. The receptor binding motif (RBM) is shown in purple. The mutations are marked according to the immune escape (green), increased infectivity (yellow) and unknown (pink) (B–D).

Figure 3

Bad news and good news about the Omicron variant. Bad news, the activity of neutralizing antibodies elicited by the SARS-CoV-2 infection and vaccines is reduced significantly. Most of the therapeutic monoclonal antibodies lose the neutralization activity. Good news, the booster vaccination can ameliorate the significant reduction. T cell immunity is minimally influenced. Antiviral drugs such as Remdesivir, Molnupiravir, Nirmatrelvir are less affected by the Omicron variant. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE2, angiotensin-converting enzyme 2; TMPRSS2, transmembrane serine protease 2; MHC-I, major histocompatibility complex class I; MHC-II, major histocompatibility complex class II; TCR, T-cell receptor; APC, antigen presenting cell. Image created by Yifei Guo using BioRender (https://biorender.com/).