Currently, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread worldwide as an Omicron variant. This variant is a heavily mutated virus and designated as a variant of concern by the World Health Organization (WHO). WHO cautioned that the Omicron variant of SARS‐CoV‐2 held a very high risk of infection, reigniting anxieties about the economy's recovery from the 2‐year pandemic. The extensively mutated Omicron variant is likely to spread internationally, posing a high risk of infection surges with serious repercussions in some areas. According to preliminary data, the Omicron variant of SARS‐CoV‐2 has a higher risk of reinfection. On the other hand, whether the current COVID‐19 vaccines could effectively resist the new strain is still under investigation. However, there is very limited information on the current situation of the Omicron variant, such as genomics, transmissibility, efficacy of vaccines, treatment, and management. This review focused on the genomics, transmission, and effectiveness of vaccines against the Omicron variant, which will be helpful for further investigation of a new variant of SARS‐CoV‐2.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.27588

Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population1. Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies2–10, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants. The replication and pathogenicity of the Omicron variant of SARS-CoV-2 is attenuated compared with the original strain and other variants. 

/pdf/attenuated-replication-and-pathogenicity-of-sars-cov-2-b-1-1-3h9hz9ki.pdf

Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus. 

/pdf/structural-basis-of-sars-cov-2-omicron-immune-evasion-and-1cnsjyr0.pdf

Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement

The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T cell responses targeting SARS-CoV-2 D614G [wild type (WT)] and the Beta, Delta, and Omicron variants of concern in a cohort of 60 health care workers after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273, or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which substantially decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays showed consistent cross-neutralization of the Beta and Delta variants, but neutralization of Omicron was significantly lower or absent. BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV2 priming partially restored neutralization of the Omicron variant, but responses were still up to 17-fold decreased compared with WT. SARS-CoV-2–specific T cells were detected up to 6 months after all vaccination regimens, with more consistent detection of specific CD4+ than CD8+ T cells. No significant differences were detected between WT- and variant-specific CD4+ or CD8+ T cell responses, including Omicron, indicating minimal escape at the T cell level. This study shows that vaccinated individuals retain T cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations are needed to further restore Omicron cross-neutralization by antibodies. Description Vaccination-induced SARS-CoV-2–specific CD4+ and CD8+ T cells targeting the ancestral spike protein cross-recognize the Omicron variant. T cells stand strong against Omicron The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern (VOC) caused an unprecedented rise in COVID-19 cases, even among vaccinated individuals. Omicron has a high number of mutations in the spike protein, probably aiding its evasion of immune responses. GeurtsvanKessel et al. studied humoral and cellular immune responses to Omicron and other VOCs to understand how vaccinated individuals are protected against Omicron. They found that antibody cross-neutralization of Omicron was very low or absent compared with WT, Beta, and Delta variants, but could be partially restored by a third booster vaccination. T cells recognized Omicron just as effectively as other VOCs, suggesting that vaccinated individuals maintain T cell immunity, which could provide protection in the absence of neutralizing antibodies, limiting severe disease.

/pdf/divergent-sars-cov-2-omicron-reactive-t-and-b-cell-responses-2azlopoa.pdf

Divergent SARS CoV-2 Omicron-reactive T- and B cell responses in COVID-19 vaccine recipients

Abstract Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant. 

/pdf/sars-cov-2-omicron-is-an-immune-escape-variant-with-an-3gfu5pci.pdf

xing feng

Papers

The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic