Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully. 

https://doi.org/10.1016/j.envres.2022.112816

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

https://www.nature.com/articles/s41591-022-01855-7.pdf

Modeling transmission of SARS-CoV-2 Omicron in China

Coronavirus disease 2019 (COVID‐19) is an ongoing pandemic, which affected around 45 million confirmed cases of COVID‐19, including more than 6 million deaths. However, on November 24, 2021, the World Health Organization announced a new severe acute respiratory syndrome coronavirus 2 variant designated as the B.1.1.529, a variant of concern (VOC), and the variant has been named as “Omicron.” Available preliminary evidence suggests that, as compared with previous VOCs, it has an increased risk of infectivity. Studies have shown that protection from various vaccines effectiveness against hospitalization and death from severe COVID‐19 disease is decreasing slowly after a two‐dose schedule of COVID‐19 vaccines. In response to experiencing a new COVID‐19 variant and ongoing resurgence of cases, the importance of COVID‐19 vaccine booster dose and durability of the effect of the third dose of vaccine against COVID‐19 Omicron variant is controversial yet. To address this, we conducted a systematic literature survey on effectiveness of the third or booster dose of COVID‐19 vaccine against the Omicron variant. We have performed a systematic search in PubMed (Medline), Google Scholar, and MedRXiv database, from inception to January 2022 using the MeSH terms and keywords “Corona Virus Disease‐2019 OR COVID‐19 AND Omicron AND COVID‐19 Booster Vaccine.” We have identified a total of 27 published studies. We have reviewed all the eligible available studies on the effectiveness of the COVID‐19 vaccine booster shots against the Omicron variant. This review may be helpful in accelerating the COVID‐19 booster dose vaccination.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.27697

Current evidence on efficacy of COVID‐19 booster dose vaccination against the Omicron variant: A systematic review

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease. Description Boosting a weakened response The Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in 2021 and is now dominant across the globe. Bowen et al. show that the Omicron sublineages BA.1, BA.2, BA.2.12, and BA.4/5 have increased affinity for the ACE2 receptor on human cells, but show decreased cell-cell fusion. They used pseudovirus to measure neutralizing activity against Omicron sublineages in plasma from individuals who were previously infected or vaccinated with one of seven vaccines, all based on the Wuhan-Hu-1 variant. For both vaccinees and convalescents, there was severe dampening of neutralizing activity. Boosting with either the same vaccine used initially or one of the other Wuhan-Hu-1–based vaccines increased neutralization across all vaccines evaluated. —VV The increasingly prevalent Omicron BA.4/BA.5 sublineages exhibit enhanced receptor binding and escape from neutralizing antibodies.

/pdf/omicron-spike-function-and-neutralizing-activity-elicited-by-3mvctzx8.pdf

Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines

http://www.cell.com/article/S1931312822002207/pdf

Neutralization of SARS-CoV-2 Omicron sub-lineages BA.1, BA.1.1, and BA.2

Abstract The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants. 

/pdf/neutralizing-antibodies-against-the-sars-cov-2-delta-and-1rwu9amo.pdf

Elena De la Cruz

Papers

Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination