key: cord-0920969-hrqt95b7
authors: Araf, Yusha; Akter, Fariya; Tang, Yan‐dong; Fatemi, Rabeya; Parvez, Md. Sorwer Alam; Zheng, Chunfu; Hossain, Md. Golzar
title: Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines
date: 2022-01-23
journal: J Med Virol
DOI: 10.1002/jmv.27588
sha: 43500c022cd3dbb2ef5bd484af541a20851095d0
doc_id: 920969
cord_uid: hrqt95b7

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.

November 2021, the Delta variant was designated as variant of concern (VOC) because of different characteristics. 1 According to the Centers for Disease Control and Prevention (CDC), the variant responsible for increased transmissibility, severe disease course, reduced effectiveness of treatments, and many other alarming factors is designated as the VOC. 2 were international travelers. 5 The Omicron variant is the most heavily mutated variant among all the VOC so far, which paves the way for enhanced transmissibility and partial resistance to immunity induced by COVID-19 vaccines. 4, 6 Following the D614G, Beta/Gamma, and Delta VOCs, the SARS-CoV-2 Omicron variant could be the catalyst for the fourth wave of the COVID-19 outbreak to sweep the globe. 7 Unfortunately, this variant has already been spotted in 80 countries worldwide until . The death of one confirmed patient infected with the Omicron variant of SARS-CoV-2 in the UK was reported on December 13, 2021. 6, 8 Therefore, it is important to pay attention and take the required steps to strengthen surveillance and undertake public health measures. As a response, the goal is to raise awareness while avoiding overreaction. 9 New COVID-19 variants, such as Omicron, remind us that the epidemic is far from ended. People must acquire the vaccination as soon as it becomes available and continue to follow existing guidelines for limiting the transmission of the virus, including physical separation, wearing masks, handwashing regularly, and keeping indoor spaces ventilated. Vaccines and other public health measures must be readily available worldwide. 10 This review discussed the genomics of the SARS-CoV-2 Omicron variant with its transmissibility and efficacy of current COVID-19 vaccines. In addition, the treatment and management were discussed along with several recommendations to keep safe from the SARS-CoV-2 Omicron variant.

The Omicron variant of the SARS-CoV-2 genome constitutes 18 261 mutations from which more than 97% mutations are present in the coding region, and the remaining 558 are detected in the extragenic region. 11 Mutations in the coding region are 2965 indels and nonsynonymous, and synonymous single-nucleotide polymorphisms (SNPs) mutations are 11 995 and 2743, respectively. 11 Thirty mutations have been found within the spike proteins mostly located at the receptor-binding domain (RBD) of the spike protein of the Omicron variant ( Figure 1 ). 12 For more than 270 million reported SARS-CoV-2 infections worldwide, the virus has evolved into over 1500 distinct Pango lineages. 13 Additionally, three other deletions and one insertion mutation are present outside the spike protein. Preliminary data analyzed from the Global Initiative on Sharing All Influenza 101 Data (GISAID) showed that NTD contains 11 mutations, including six deletions and one insertion, with mutations N211 and ins214EPE being unique. 14 Interestingly, some of the mutations were already found in the previous VOC that helps in neutralizing antibodies. 15, 16 Five different variants of SARS-CoV-2 have been considered VOC at different times. 17 Investigations performed by epidemiologists in South Africa identified the mutational data that manifests some of the concerning mutations (N501Y, D614G, K417N, and T478K) along with new mutations present in the Omicron variant, which increased the overall risk of reinfection, partial resistance to existing vaccines 17 ( Figure 1 ).

Omicron. The first, a lysine to asparagine substitution at position 417, has been linked to S protein structural alterations that may enhance immune evasion. The second mutation, a threonine to lysine substitution at position 478, is likely to boost the residue's electrostatic potential and steric interference, perhaps increasing RBD binding affinity and allowing immunological escape. A leucine to arginine substitution at position 452, which is present in Delta but not in the Omicron variant, is known to boost affinity for ACE2 receptors found on the surface of various human cells, including the lungs. 18 Even though Wuhan-Hu-1 has 1273 amino acids, the Delta variation has 1271, and the Omicron variant has 1270, both contain fewer residues than the wild-type due to sequence loss. 19 Genome analysis by Kandeel et al. reported that the Omicron variant of SARS-CoV-2 forms a new monophyletic clade. 20 On the other hand, Wang et al. showed that the Omicron variant of SARS-CoV-2 evolved from the 20B clade and formed two subclades. 21 

There is still a scarcity of sufficient essential data regarding the infection rate to analyze the transmissibility of the new heavily mutated Omicron variant. However, analysis from the early data of South Africa manifested that the Omicron variant can spread way more easily from person to person, though experts could not draw any conclusion within this short period. 22 The concern of Omicron variant transmissibility increases as it spreads worldwide within a few days, and cases have been increasing dramatically. 23 According to the report of CDC, a 2.5% increasing capacity of Omicron variant has been observed in the US within 2 weeks. However, in New York/New Jersey area, the infection rate is around 13%. On the other hand, in Britain, Omicron variant cases doubled every 2-3 days. 22 The infection rate of the Omicron variant in South Africa is increasing faster than any other country's three previous waves. On November 30, the number of cases was 10.3%, shifting to 16.5% within two days.

Surprisingly, on December 2 and 3, cases were 22.4% and 24.3%, respectively. 24 When the linear regressions of each pseudovirus were compared to the wild type over the entire range, it was discovered that while the Gamma variant had similar infection rates to the wild type, the Beta variant had less infection, and Delta was nearly twofold more efficient at infecting target cells. Infection rates were four times higher in the Omicron variant than in the wild type and twice as high in the Delta variant. These findings indicate that spike sequence influences infectivity, with the Omicron variant displaying more effective ACE2-mediated infection than the wild type or other variant strains. 13 Numerous factors can influence the high transmissibility of the Omicron variant. Genome sequenced data of the Omicron variant demonstrated more than 30 mutations in the spike protein by which the SARS-CoV-2 protein recognizes host cells. 25 Analysis of these mutations data indicates the chance of increased transmission by evading the immune response. 26 The N501Y mutation increases the binding affinity with the ACE2 receptor, which is a major influencer of increased transmission, and in combination with Q498R, the binding affinity gets stronger, and the Omicron variant gets easy access into the host. 26 Moreover, the risk of reinfection of previously COVID-19 infected patients with the Omicron variant is very evident, indicating higher transmissibility. 15 Omicron variant mutations H655Y and N679K are present near the furin cleavage site (FCS) and

can increase spike cleavage, making the virus more contagious. 27, 28 On the other hand, P681H can multiply transmissibility by increasing the spike protein cleavage. 29 Furthermore, the new variant Omicron gives a false negative result in polymerase chain reaction tests because of the "S gene target failure," which paves the way of spreading the infection at a higher speed worldwide. 4 A previous study suggested a likely relationship between the positive electrostatic potential and affinity in the Delta VOC. 30 The increased electrostatic potential is 35 The heavy mutation in the spike protein of the Omicron variant is related to increased infectivity and antibody evasion. 36 In SARS-CoV-2 convalescent or vaccinated people, the amount of neutralizing epitopes targeted by polyclonal antibodies is a significant predictor of the genetic barrier to viral escape. Single monoclonal antibodies are susceptible to escape mutations, but combinations targeting nonoverlapping epitopes are more resistant. 37 Surprisingly, Omicron variant neutralization was undetectable in the majority of vaccines. 14 The computational approach also demonstrated that antigenic properties of the Omicron variant are ominous and correlated with its mutations. 38 Although various investigations have been performed to create effective vaccines, the emergence of new VOCs has raised concern over the efficacy of neutralizing antibodies induced by COVID-19 vaccines as the Omicron variant has already infected vaccinated individuals in South Africa, Hong Kong, and many other countries. 36, 39, 40 The potential impact of the COVID-19 vaccine is still being analyzed against this new variant. Two BNT vaccinations, which can provide more than 90% protection against serious disease when infected with the Delta variant, maybe significantly less effective against the Omicron type of SARS-CoV-2. 14 However, the effect of COVID-19 vaccines against the previous VOC, such as Delta, manifested the vaccine's potential in reducing severe disease and death. 41 Moreover, multiple Delta transmissions from and between completely vaccinated persons were confirmed using genomic and epidemiological data. 42 As vaccine-induced immunity is targeted through the spike proteins of the virus, heavily mutated Omicron variant spike protein is capable of reducing the neutralization activity of sera of vaccinated individuals that indicated less protection from Omicron variant. 26 Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibodies against the Omicron variants HKU691 and HKU344-R346K, respectively, but none of the Coronavac recipients did. The geometric mean neutralization antibody titers (GMT) of the Omicron variant isolates were 35.7-39.9fold lower than the ancestral virus for BNT162b2 recipients, and the GMT of both Omicron isolates were significantly lower than the Beta and Delta variants. Between HKU691 and HKU344-R346K, there was no discernible difference in GMT. 43 City will be required to be vaccinated. 54 Similarly, the UK government has announced different measures, such as mandatory masking in all public places, isolation for ten days if contact with an Omicron variant infected individual, and compulsory self-isolation for travelers. 4 F I G U R E 2 The total number of confirmed Omicron variant cases per country and the probability of identifying a case. The figure shows that South Africa sequences many more samples than any other African country, but slower than most Western countries. Additionally, returning a viral sequence might take up to 2 weeks in countries with technical competence. Thus reliable statistics on verified instances lag behind the actual situation. Cases detected using their variant qPCR test, which is rather fast and tests numerous genes, are considered sufficient for counting as an Omicron variant by Norway and Denmark, even before full sequencing. So, it can be said that the sequencing rate influences the probability of discovering a case ARAF ET AL.

One of the most densely populated countries, India, has taken five steps to combat the new COVID-19 spread. The mandatory risk profile of each individual, institution-wide quarantine, genome sequencing of samples, intensive contact tracing of suspects, and strict adherence to COVID-19 appropriate behavior are among them. 55 Bangladesh, a low-income country, has announced a plan to tackle the Omicron strain, though it is yet to be discovered in Bangladesh.

The plan includes travelers from South Africa, Namibia, Zimbabwe, Botswana, Eswatini, Lesotho, and other new variant-infected countries listed by the WHO that should be exposed to increased medical testing and screening. Whether social, political, religious, or otherwise, any type of public gathering must be avoided. Facemasks must be worn when leaving the house, and all other basic health needs. 56 The introduction of the Omicron variant is causing concern in countries worldwide, emphasizing the significance of pandemic preparedness. 51 However, there is growing hope that the Omicron variety of SARS-CoV-2, becoming more prevalent, will cause less severe disease than prior strains. Researchers in England, Scotland, and South Africa discovered that the Omicron variation has a 15%-80% reduced risk of hospitalization than the delta variant.

Despite far greater case counts, surveillance data shows that the latest omicron-driven wave of illnesses has significantly fewer hospital admissions and deaths than past waves. 57 

Omicron variant-positive patients in South Africa showed very mild symptoms, and no oxygen support was required until now. 58 However, the UK is facing a different scenario in the case of Omicron variant-positive patients. In an interview with Global Health Crisis Coordination Center, vaccine expert Shabir Madhi said that "In the South African much of the immunity that currently exists is large because of the prior infection that has taken place during the first three waves." Thus, being ready with all the existing treatment and management procedures for any unfortunate situation is a must. 59 A recovered Omicron variant positive patient from India shared his recovery journey and informed that he did not experience any concerning symptoms and tiredness while in hospital in contrast to the period he had been in hospital with Delta. Based on the severity of the infection, he had been given vitamin C and antibiotics. 60 Dr. Angelique Coetzee, one of the first doctors in South Africa treating Omicron variant positive patients, informed that the symptoms of the disease are just a sore throat, fatigue that stays for a day; thus, meeting with a health professional and getting tested is compulsory to have efficient treatment as per need. 61 According to health experts Kumar and Wu, antiviral pills from Pfizer and Merck can efficiently treat mild to moderate COVID-related illnesses. 62 Different laboratory findings have manifested the usefulness of sotrovimab, a monoclonal antibody found in the blood of recovered SARS patients, as it has the potential of blocking SARS and SARS-CoV-2. 63 According to recent data, corticosteroids and IL6 receptor blockers are still effective in treating people with severe COVID-19 cases. 41 To manage the upcoming surge, WHO recommends that countries improve surveillance and sequencing of cases, share genome sequences on publicly available databases like GISAID, report initial cases or clusters to WHO, and conduct field investigations and laboratory assessments to understand better if Omicron variant has different transmission or disease characteristics, or has an impact on vaccine effectiveness. 41 WHO issues travel advisory due to the Omicron variant. People aged 60 and above and those with particular health concerns are advised to limit the trip plans for the time being.

Experts recommended vaccines and maintained up to date on all injections until further information is available since they may still protect people from all variants of the SARS-CoV-2. 64 Individuals infected with the new variant must be isolated. 65 ACKNOWLEDGMENT This study has not been supported by any grant.

The authors declare that there are no conflict of interests. 

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separate-isolation-area-for-omicron-positive-patients-must-healthministry-121120800951_1.html How to cite this article

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

http://orcid.org/0000-0002-0144-5875Fariya Akter https://orcid.org/0000-0001-8920-4218Yan-dong Tang https://orcid.org/0000-0002-5690-2690Rabeya Fatemi https://orcid.org/0000-0003-1490-4724Md. Sorwer Alam Parvez https://orcid.org/0000-0002-9726-1009Chunfu Zheng http://orcid.org/0000-0002-8797-1322Md. Golzar Hossain https://orcid.org/0000-0002-1487-5444