Why Omicron may usher in the end of a deadly pandemic

Sars-CoV-2, like any other RNA virus, has been continuously exhibiting variations in viral genes (mutations), with increased transmissibility and infectivity due to these alterations. The virus and its derivatives were responsible for the deaths of millions of people in many parts of the world. The most recent version is the Omicron variant, which has alterations in its spike protein that are unparalleled in the history of the virus.

Although the hazards of transmissibility and immune evasion have not been thoroughly investigated in the variant, it is evident that Omicron (B.1.1.529) has several changes that may impact transmissibility and immune evasion.

Also read: Omicron to hit over 50% of people from Nov 2021 to March 2022: Expert

During research, Leyun Wu and colleagues discovered that the spike protein of Omicron contains 34 mutations compared to its wild type. As they report, 15 of them are located in the receptor-binding domain (RBD), and 10 are located in the receptor-binding motif (RBM), both of which are directly engaged by ACE2 and the majority of monoclonal antibodies (mAbs).

Another research claimed to have discovered 46 Omicron-specific mutations with a high incidence in the population. Twenty-three of these are located in the spike protein (S), with the other three structural proteins being present in the virus’s other three structural proteins (envelope, membrane, and nucleocapsid). Their phylogenetic investigation discovered that the Omicron is linked to the Gamma (P1) variant. The structural study of the Omicron variant conducted as part of the research reveals several alterations in the antibody-binding domain of the S protein, suggesting that the mutations in the Omicron variant may affect antibody binding affinities to the S protein.

The Delta (B.1.617.2) variant contains only two RBM mutations (L452R and T478K), with occasional K417N and E484K alterations. The high amount of alterations in the spike protein indicates that the Omicron variant may affect mAb binding affinity to ACE2 and thus impact the efficacy of vaccines.

In a comprehensive quantitative analysis of Omicron’s infectivity, vaccine breakthrough, and antibody resistance conducted by Jiahui Chen et al., the researchers discovered that Omicron is approximately 10 times more infectious than the original virus and about 2.8 times more contagious than the Delta variant. According to their findings, based on the architectures of 185 known antibody RBD complexes, Omicron has a vaccine-escape potential roughly 14 times greater than the Delta version.

It is claimed that Omicron hinders antibody neutralisation of vaccination and infection-induced antibodies. However, the exact mechanism by which it affects T cell responses is unknown. Research by Syed Faraz Ahmed suggests that the T cell responses to Omicron mutations on existing T cell epitopes are resistant to this novel variation.

The RBD/ACE2 interaction is just one of the numerous mechanisms necessary for viral cellular entry. These alterations may influence the overall viral structure, the conformational changes required to “load up” RBD for ACE2 binding, and the proteolytic activation of the S protein, to name a few possibilities.

According to a panel of experts from the World Health Organization, Omicron and future coronavirus strains should be included in the current COVID-19 immunization schedule. There is, however, some good news to report as well. While the efficacy profile of the current vaccinations against the Omicron version is yet to be determined, some recent research shows that they may be successful in combating the Omicron variant, at the very least when administered with a booster dose of the original vaccine.

Also read: All about Omicron: Recovery time, symptoms and severity

According to laboratory findings in the United States, the vaccine stimulates a considerable immune response from T cells, which protect against severe illness even if they do not totally prevent the virus from infiltrating the body. There is enough information to distinguish between two distinct patterns. According to the first finding, there is a more than 19x titer fold decrease of Omicron in those who have been twice vaccinated, and it may be considerably higher given the quantity of data available below the assay’s limit of detection. Second, the titer fold decrease to Omicron is around 7x up to one month after the third mRNA vaccination or twice after a previous infection, whichever comes first. The fact that the fold drop was minimized and the titers were somewhat higher after the third immunization supports the effectiveness of booster vaccination.

Following a booster dose, the J&J vaccine’s effectiveness against COVID-19 hospitalization climbed to 85 per cent, despite the presence of the Omicron variation in circulation. The J&J team shared the findings. The South African squad has already released a preprint of these results online and is preparing to submit it to a peer-reviewed publication.

In his remarks, the CEO of Pfizer said that the Omicron is more difficult to target. The variant, which had hundreds of mutations, may be able to avoid some of Pfizer’s first two injections. The present vaccination, according to him, offers considerable protection against deaths and hospitalizations when administered in the third dose. There are reports that Pfizer is working on a novel vaccine targeting the Omicron virus and subsequent versions.

In addition, based on a study done by Oxford University, AstraZeneca claims that after two doses of its vaccine, the neutralizing levels against Omicron were equal to those against the delta variant.

Researchers examined the risks of hospitalization and mortality associated with both Omicron and Delta variants in a new study released on the preprint platform medRxiv. According to this study, the probability of hospitalization or death was 68 per cent lower in the Omicron cases. Even after correcting for vaccination status, the risk of hospitalization or mortality in individuals infected with Omicron was shown to be 54 per cent lower.

One early explanation proposed by scientists for the greater transmissibility and lower severity of the Omicron type is that the virus replicates more readily in the bronchi (air passages of the lungs) than in the lung parenchyma (the functional tissue).

Also read: Avoid steroids, test for TB if cough persists – Centre updates COVID guidelines

Many opine that Sars-CoV-2 has reached a level where it is now the time to handle it like any other minor viral infection like a common cold or flu. Although it is too early to make such a conclusion, it is evident that the character of the virus is significantly changing as more and more variants emerge. Let’s hope the virus loses its ability to cause disease and infectivity soon.