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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 69-72

Omicron: An emerging variant of concern


Department of Medicine, MVJMC and RH, Bengaluru, Karnataka, India

Date of Submission30-Dec-2021
Date of Decision10-Jan-2022
Date of Acceptance10-Jan-2022
Date of Web Publication02-Mar-2022

Correspondence Address:
Dr. Vasantha Kamath
Department of Medicine, MVJMC and RH, Hoskote, Bengaluru - 562 114, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_134_21

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  Abstract 


Emerging infectious diseases are now a concern worldwide and can evolve into a global health-care crisis or pandemic. Identification of the Omicron variant (B.1.1.529) of severe acute respiratory syndrome-2 (SARS-CoV-2) which is considered a variant of concern has added fuel to the eternal flame of the global COVID-19 pandemic. There is an apparent sharp rise in cases of the new variant which is setting off alarm bells. The emergence of this new strain of the virus has taken a disproportionate toll in few countries including India. The need of the hour is to track the concerning rise of the new variant of the SARS-COV-2 causing COVID-19 and to prevent the reinfection.

Keywords: OMICRON, reverse transcription-polymerase chain reaction, severe acute respiratory syndrome-2, technical advisory group on virus evolution


How to cite this article:
Kamath V, Reddy D. Omicron: An emerging variant of concern. APIK J Int Med 2022;10:69-72

How to cite this URL:
Kamath V, Reddy D. Omicron: An emerging variant of concern. APIK J Int Med [serial online] 2022 [cited 2022 May 29];10:69-72. Available from: https://www.ajim.in/text.asp?2022/10/2/69/338897




  Introduction Top


The enduring decline in COVID-19 cases following the second wave in India had led to a hope that a return to ordinariness might be near. As the restrictions had eased and public behavior was largely back to normal, the evolving Omicron variant has become an ongoing challenge to the world. On November 26, 2021, the World Health Organization designated the variant B.1.1.529 named a variant of concern, named Omicron, on the advice of the WHO's Technical Advisory Group on Virus Evolution.[1] Omicron is designated as a variant of concern because it has an unusually large number of mutations which are considered novel. Transmissibility, immune system evasion and destruction, and resistance to vaccines cause a huge concern due to its extended level of variation.


  History Top


On November 24, 2021, a new severe acute respiratory syndrome -2 (SARS-CoV-2) variant, B.1.1.529, was first identified and reported by South Africa to the WHO. According to sources available, the first known sample was dated back to November 9, 2021. Scientists on the other hand were alerted when the polymerase chain reaction (PCR) tests showed S-gene target failure (SGTF) or S-gene dropout and the main concern was the sudden increase in COVID-19 cases in Gauteng.[2] The first confirmed specimens of Omicron were collected on November 8, in South Africa and November 9, in Botswana. Four cases reported initially were from Botswana and were fully vaccinated. Omicron is a variant of concern as it has a maximum number of mutations and further investigation is a must to evaluate its potential behavior and impact on the individuals. As per the recent sources and evidence collected, this variant has a maximum growth advantage and risk of reinfection. Detection of the variant at faster rates in turn decreases the surge in infection and is of paramount importance.


  Epidemiology Top


On November 26, 2021, the South African National Institute for Communicable Diseases (NICD) announced that 30,904 COVID-tests in 1 day detected 2828 new COVID infections (a 9.2% positivity rate).[3] On December 3, 2021, that is 1 week later the NICD announced that 65,990 COVID tests had found 16,055 new infections (5.7 times as many as 7 days before; positivity rate 24.3%) and that 72% of them were found in Gauteng.[4] Omicron is frequently able to infect previously COVID-19-positive people.[5] Sequencing data suggest that Omicron had become the dominant variant in South Africa by November 2021, the same month where it had been first identified in the country.[6] Data revealed Omicron has a pronounced growth advantage in South Africa due to transmissibility or immune escape related, or both.

In the United Kingdom, the logistic growth rate of Omicron-associated SGTF cases over S-gene target-positive cases was estimated at 35% per day, which is exceptionally high.[7] Furthermore, by mid-December, Omicron will be growing past Delta. Without presuming behavior change in response to the variant, a million infections per day by January 1 are projected for 2.5 days doubling time.[8]

Confirmed cases have been reported by 22 countries highest reported in Denmark and the least number of cases in Croatia and Cyprus, according to information from public sources.[9]

India has reported a total of 781 cases of Omicron variant of COVID-19 to December 29. Delhi accounts for the highest number, followed by Maharashtra.

Currently, Karnataka reports 38 new Omicron cases to date.


  Why is it Called Omicron? Top


The WHO has been naming new virus strains as per the Greek alphabet. This method was chosen by the global health body on May 31, 2021. The idea was to ensure that variants had easy-to-say and remember labels.[10] The naming system was also designed to avoid geographical stigma being assigned to a COVID-19 variant. Going by the WHO method, the new strain that was first found in South Africa should have been either named “Nu” or “Xi”. Few people speculated that the group skipped Nu to avoid confusion with the word “new.” They also added that Xi was skipped in an effort to avoid antagonizing China. According to the WHO, Xi was skipped to “avoid stigmatizing a region.”[11]


  Genome Sequencing Top


The primary purpose of genome sequencing is to obtain information on genetic variants that can increase the risk of disease development. Omicron variant has around 60 mutations in total when compared to the original Wuhan variant. Around 50 nonsynonymous mutations, 8 synonymous mutations, and 2 noncoding mutations have been observed.[12] In these, 32 mutations affect the spike proteins which are the main antigenic target. A study suggests that Omicron has picked up one of its mutations, ins214EPE, from HCoV-229E, a common cold coronavirus strain, a genetic sequence also present in the human genome. This appears to aid the virus in circumventing the human immune system.[13],[14] The variant is characterized by 30 amino acid changes, three small deletions, and one small insertion in the spike protein compared with the original virus, of which 15 are located in the receptor-binding domain (residues 319–541). It also carries a number of changes and deletions in other genomic regions. In addition, the variant has three mutations at the furin cleavage site.[15] The severity of SARS-CoV-2 infection is increased by the furin cleavage site. Depending on the genomic regions, the mutations are as follows.

Spike protein

A67V, Δ69–70, T95I, G142D, Δ143–145, Δ211, L212I, ins214EPE, G339D, S371 L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F.

Half of these mutations are located in the receptor-binding domain.

  • ORF LAB


    • nsp3: K38R, V1069I, Δ1265, L1266I, A1892T
    • nsp4: T492I
    • nsp5: P132H
    • nsp6: Del105–107, A189V
    • nsp12: P323 L
    • nsp14: I42V


  • Envelope protein: T9I
  • Membrane protein: D3G, Q19E, A63T
  • Nucleocapsid protein: P13 L, Δ31-33, R203K, G204R.[16],[17]



  When do we Call it as a Variant of Concern? Top


The WHO designated Omicron as a variant of concern as the virus has been demonstrated to be associated with the following changes, which can lead to the global health crisis.

  1. When there is an increase in transmissibility and huge change in COVID-19 epidemiology
  2. When there is change observed in clinical presentation of the disease
  3. When the effectiveness of public health and social measures and vaccines decreases.



  What is Variant of Interest? Top


  • Variant of interest is designated when there is a SARS-CoV-2 variant with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, disease severity, and immune escape, diagnostic, or therapeutic escape
  • When it has been identified as causing significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence alongside increasing the number of cases over time, or other apparent epidemiological impacts to suggest an emerging risk to global public health.



  Delta Variant Versus Omicron Variant Top


The outcome of the genome sequencing has revealed that the Omicron variant is highly mutated as compared to the Delta variant.[18] This variant has been shown to carry a high number of mutations, 32, on the spike (S) protein, which happens to be the main antigenic target of antibodies that are generated by either infections or vaccination. Whereas, the Delta variant has only 5 S protein mutations, which posed a high potential global risk and has spread internationally. Therefore, the panic button has been pushed in several cases worldwide, and many countries have enacted travel restrictions to prevent the rapid spread of the Omicron variant. The chief concerns that have arisen about Omicron are – first, if it is more infectious or severe than other Variants of Concern (VoCs) and second, whether it can circumvent vaccine protection. Owing to a lack of immunological and clinical data with definitive evidence, we will have to deduce the answers to our questions from what is currently known about the mutations of Omicron to provide preliminary indications on transmissibility, severity, and immune escape.[19] Omicron has some deletions and more than 30 mutations, many of which overlap with those in the alpha, beta, gamma, or delta VoCs (namely, 69–70del, T95I, G142D/143–145del, K417N, T478K, N501Y, N655Y, N679K, and P681H). These deletions and mutations are known to enhance transmissibility, viral binding affinity, and antibody escape.


  Transmissibility Top


The efficiency of Omicron variant to speed up the spread from person to person is highly unknown. Concerns about the replacement of Delta by Omicron as the predominant variant in South Africa raises issues that the Omicron variant may be more transmissible than Delta. As the numbers of cases in South Africa were minimum when Omicron emerged, it is unclear if this variant is more transmissible than the Delta variant. It is difficult to estimate the transmissibility, as relatively very few cases have been documented making it a concern. Analysis of the changes in the spike protein indicates that the Omicron variant is likely to have increased transmission compared to the original SARS-CoV-2 virus, but it is difficult to infer if it is more transmissible than Delta. Epidemiological studies are on the go to understand transmissibility.

  • N501Y increases binding to the ACE2 receptor, which could increase transmission and the combination of N501Y and Q498R, may increase binding affinity even more. Receptor binding affinity needs to be assessed using the full spectrum of spike protein substitutions found in the Omicron variant
  • H655Y is proximal to the furin cleavage site and may increase spike cleavage, which could aid transmission
  • N679K is proximal to and adds to the polybasic nature of the furin cleavage site, which may also increase spike cleavage and could aid transmission
  • P681H has been shown to enhance spike cleavage, which could aid transmission. This mutation is found in alpha and an alternate mutation at this position (P681R) is found in Delta.[20]



  Disease Severity Top


There is no clear evidence whether infection with Omicron causes more severe disease compared to infections with other variants, including Delta. Data collected preliminarily suggest that there are increasing rates of hospitalization in South Africa, but this may be due to increasing overall numbers of people becoming infected, rather than a result of specific infection with Omicron. Currently, there is very minute information suggesting that symptoms associated with Omicron are different from those from other variants. Initially reported infections were among younger individuals who tend to have more mild diseases. Understanding the level of severity of the Omicron variant will take days to several weeks. All variants of COVID-19, including the Delta variant that is predominant worldwide causing wildfire, can cause severe disease or death in most vulnerable people. Thus, prevention is always key to avoid transmission and disease severity.[21]


  Can Reverse Transcription Polymerase Chain Reaction Tests Reveal Omicron Variant? Top


The reverse transcription-PCR (RT-PCR) test is considered to be the “gold standard” for detecting COVID-19. The emergence of the Omicron variant has shifted the focus on RT-PCR as a highly accurate identifier of infection. That's because it has been found that in certain cases, a positive RT-PCR test can also give a good idea if the infection is caused by this newest variant of concern. However, there is an important forewarning: not all RT-PCR tests can identify Omicron, which further, is not the only variant thus susceptible to detection.[22]

RT-PCR test works by detecting the presence of specific genetic material in a pathogen. In the case of the novel coronavirus, most RT-PCR tests seek out genes in its spike protein, which the virus uses to invade human cells. In RT-PCR tests, more than one spike protein is targeted, so that even if a mutation may have changed one of the genes, the other genes would still get captured in this test.

The WHO named this phenomenon as S-gene dropout or SGTF which means that specific RT-PCR tests can “therefore be used as marker for this variant, pending sequencing confirmation.”


  Omicron and Vaccine Efficacy Top


A preliminary study indicated that Omicron variant could reduce the effectiveness of certain COVID-19 vaccines. Recent laboratory study found that Omicron lessened the Pfizer and BioNTtech vaccine's protectiveness after two doses, although a third dose may restore the protection. There are huge suspicions and concerns that Omicron variant could become the dominant strain of COVID-19, replacing the Delta variant. Delta currently makes up 99.8% of global COVID-19 cases according to the WHO.[23]

Studies of other COVID-19 vaccines from Moderna, AstraZeneca, and Johnson and Johnson are underway. Further studies are yet to be done to analyze the impact of the Omicron variant on blood samples from previously infected and vaccinated people. Many scientists expect these vaccines will show a reduction in their ability to neutralize Omicron compared with earlier coronavirus variants. Moderna vaccine uses similar technology as Pfizer/BioNTech but has been shown to offer more durable protection against infection with previous variants, a benefit believed to be due to its higher dose and longer interval between shots. Data are still needed on how protective COVID-19 vaccines remain in real-world use against the highly mutated Omicron variant. The two latest vaccines Corbevax and Covovax were granted by India under emergency use authorization which is the cutting edge. A groundbreaking antiviral COVID-19 pill molnupiravir is in a remarkable move.


  Prevention Top


As we all know that “An ounce of prevention is worth a pound of cure.” It is always the key. Preventive measures should be inculcated to reduce the chances of infection which include vaccination, staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, managing potential exposure durations, washing hands with soap and water often and for at least 20s, practicing good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.


  Conclusion Top


Worldwide evidence suggests that the Omicron variant is associated with considerable ability to evade immunity from prior infection. Among the evasion, there is no population-wide epidemiological corroborative evidence of immune escape associated with the variants. This finding has important connotations for public health planning, particularly in countries such as South Africa with high rates of immunity from prior infection. Compelling questions exist regarding whether Omicron can evade vaccine-induced immunity and the potential inference of narrowed immunity to infection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  In this article
Abstract
Introduction
History
Epidemiology
Why is it Called...
Genome Sequencing
When do we Call ...
What is Variant ...
Delta Variant Ve...
Transmissibility
Disease Severity
Can Reverse Tran...
Omicron and Vacc...
Prevention
Conclusion
References

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