In 2019, the SARS CoV-2 coronavirus began as a pneumonia outbreak in Wuhan, China. Now, it has assumed global proportions. It has claimed about 5.6 million lives and affected over 260 million people around the world. As we have entered the third year of the pandemic, it is still not clear for how long coronavirus would continue to mutate and dictate human lives.
As the SARS-CoV-2 virus spreads, its mutations become quite frequent and within a short time the emerging variants with high transmission efficiency become dominant and replace other variants. The changes in variations allow the virus to be more contagious than before. RNA viruses are more error-prone than DNA viruses. SARS CoV-2 genome is a stranded RNA virus and hence mutations occur frequently.
Coronavirus variants and their mutations Scientifically, contagious viruses mutate over time and geography, weaken only after taking deadlier forms causing wide scale disaster and deaths. New coronaviruses are built by an infected cell, and while building them, it occasionally makes tiny copying errors. These are called mutations. A mutation is a change that occurs in the DNA sequence, either due to mistakes when the DNA is copied or as the result of environmental factors. Mutations are passed down through a lineage that is a branch of viral family tree. A particular family of coronaviruses that share the same inherited set of distinctive mutations is called a variant.
There are many variants of SARS CoV-2 coronavirus which has come up over the period of two years of the pandemic. The changes in the variants occur when there is a mutation of the genes of the virus. Geographic separation tends to result in genetically distant variants. In the light of such developments, the new mutations are bound to be several and distinct from one another.
Classification of variants by the World Health Organization (WHO) The WHO has classified each emerging variant as either a variant of concern (VOC) or a variant of interest (VOI). The Alpha, Beta, Gamma, Delta, and Omicron variants fall under VOC. The Eta, Iota, Kappa, Lambda, and Mu fall under VOI.
Variant of concern According to the WHO, if a SARS CoV-2 variant translates to a rise in transmissibility, an increase in fatality and significant decrease in effectiveness of vaccines, therapy, and other health measures, it is called a variant of concern (VOC). Typically, a variant is designated as a VOC, if it has evidence that supports one of the three possible factors:
- Increase in transmissibility or a detrimental change in COVID-19 epidemiology
- Increase in virulence or change in clinical disease presentation
- Decrease in effectiveness of public health and social measures including vaccines, therapeutics, and diagnostics.
Variant of Interest According to the WHO, if SARS CoV-2 variant with a genetic capability that affects the characteristics of the virus such as disease severity, immune escape, transmissibility, and diagnostic escape is called as a variant of interest (VOI). The WHO has further stated that a VOI causes consequential volume of community transmission. A global increase in cases poses a risk of large proportions to worldwide public health.
Cause of Concern The concern in VOC comprises three worrisome traits related to transmission efficiency, disease severity, and escape from immunity cover of vaccination.
In many countries, including India, the VOCs, by virtue of increased transmissibility, have kicked off new waves of epidemic. When the cases were low, during that time, there was widespread relaxation of COVID-appropriate behaviour and this contributed to a surge in cases.
The UK variant was worse in terms of virulence. The South Africa and Brazil variants did not have much propensity to cause severe life-threatening disease.
The immunity cover offered by vaccination using antigens made from D614G variant, which applies to most vaccines that are currently in use is the third concern. Lowered vaccine efficacy was found more with the South African and less with the Brazil variant. Hence, reinfection could occur in spite of immunity due to D614G vaccination.
Sweden’s Karolinska Institute has developed an antigen using a new variant RBD (Receptor Binding Domain) peptide with adjuvant. It was inoculated to monkeys, which were already primed with an older vaccine. The resultant booster response was high and broad covering new variants. This process of vaccination is called ‘hetero boosting’ by a different vaccine. It offers a way to manage the ‘vaccine escape’ variants until newer vaccines are available.
Identification and documentation of virus variants The ability to detect and track variants depends on the laboratory capacity for whole genome sequencing of viruses. Till now, over one million SARS CoV-2 genomes have been sequenced globally, providing a high-resolution, spatio-temporally granular readout of virus evolution. This has allowed the identification and documentation of variant viruses with altered properties, compared to the virus that primarily caused the pandemic. To identify the VOC of SARS CoV-2, the Indian SARS CoV-2 Consortium on Genomics (INSACOG), a network of 10 competent public-sector laboratories for genomic surveillance was established in 2020, and the genetic variant landscape is being surveyed in India.
Naming the SARS CoV-2 variants There are three different schemes of nomenclature (naming of the variant) of SARS CoV-2 variants. The widely used one is the Phylogenetic Assignment of Global Outbreak Lineages (PAN-GOLIN). This software tool uses a hierarchical system based on genetic relatedness which is an invaluable tool for genomic surveillance. The variants are given scientific names that represent their parentage and the chain of evolution. It uses alphabets and numerals, for example Omicron is also known by its more scientific designation B.1.1.529. It shows that it has evolved from the B.1 lineage, or the common ancestor.
As the scientific names are not easy to remember, the three most prevalent variants are named after the country, where they were first reported, for example, UK variant, India variant, South Africa variant, etc. But this practice of naming after specific countries led to name calling and blame game.
The WHO hence, decided on a new naming system using Greek letters. The variant that earlier used to be referred as India thus got the name Delta, while the one being associated with the UK was named Alpha.
New Variants and their Biological Characteristics
B.1.1.7 or the Alpha variant This variant was first detected in Southern England in 2020. An Oxford study revealed that after adapting to covariables, patients receiving primary care, and infected with the Alpha strain, were more likely to die in 28 days than those infected by other strains of the virus. The study also clarified that the B.1.1.7 variant was identified with a doubled probability of requiring a coronary care unit (CCU) admission. The patients who were inflicted with this variant were notably younger. Infection of this variant requires mechanical ventilation in the first 24 hours of admission.
B.1.351 or the Beta variant The Beta variant first appeared in South Africa. This viral strain may have the potential to re-infect individuals who have recovered from earlier stains of the virus. It may be resistant to some vaccines and the strain has a greater viral load compared to its previous strain.
P.1 or the Gamma variant The Gamma variant was detected in the US in January 2021. The initial cases were identified in a group of travellers from Brazil who had to undergo testing during the routine screenings at an airport in Japan. According to the Global Virus Network (GVN), this variant showed pronounced transmissibility. Its mutations, namely, N501Y, K417N, and E484K, in the ‘receptor building domain of spike protein’, tend to amplify their affinity to human receptors. With each mutation, the virus becomes more contagious than its previous strains and easily escapes immune responses of the body.
B.1.617.2 or the Delta variant This variant was initially detected in India in December 2020. Yale University’s Yale Medicine Organisation stated that vaccination is the key to combat this highly contagious strain. Delta was first designated as VOI by the WHO in April 2021 and further upgraded to VOC on May 11, 2021, taking into consideration, the emerging evidence on the transmissibility, epidemiological correlations from India as well as experimental evidence from around the world. The Delta variant quickly became the dominant strain, triggering a devastating second wave in India and spreading across the globe. To date, most confirmed COVID-19 cases are those caused by the Delta variant.
B.1.617.1 or the Kappa variant According to the WHO, the first samples of the mutant virus Kappa variant was documented in India in October 2020.
C.37 or the Lambda variant The variant was first detected in Peru in December 2020. It is said to be more contagious than the Gamma or Alpha variants. As per a New York study in July 2, 2020, the variant may be resistant to antibodies emerging from the mRNA vaccines.
B.1.621 or the Mu variant This was the fifth variant of the virus of the WHO’s list of VOI added on August 30, 2021. It was first detected in January 2021, in Columbia, the variant was also detected in the US, Hong Kong, UK, and Europe. So far it has shown signs of possible resistance to immunity developed from past infection or vaccination. This variant has a constellation of mutations that indicate potential properties of immune escape.
B.1.1.529 or the Omicron variant On November 26, 2021, the WHO declared the B.1.1.529 strain of COVID-19 as a VOC and named it Omicron. The WHO named it after the 15th letter of the Greek alphabet, skipping “nu” and “Xi”. Nu was not used due to its phonetic closeness to “new”, and ‘Xi’ was not used because it is a common surname in Asia, especially in China. This practice of naming is meant to avoid offence to any cultural, social, national, regional, professional, or ethnic groups.
It was first detected in South Africa. Omicron had a whooping 32 mutations in the spike protein alone. Confirming Omicron as a variant and a VOC, the WHO bypassed the stage of initially designating it as a VOI. The rapid pace at which WHO designated Omicron a VOC was based on concrete scientific evidence, which came early from Africa.
Omicron was seen spreading faster than the Delta variant and causing infections in people who were already vaccinated. It even affected those who recovered from COVID-19. According to the WHO, the variant was successfully evading some immune responses. This forced many countries, including India, to roll out booster vaccine programmes for people with weaker immune system and frontline workers.
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