Delta variant of COVID-19: A simple explanation

Severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease (COVID-19), has undergone numerous mutations since its initial identification, leading to challenges in controlling the pandemic. Till date, several variants of concern have been identified. However, currently, the Delta variant (B.1.617.2) is the most dreaded one owing to its enhanced transmissibility and increased virulence. In addition, this variant can potentially facilitate fusion of the spike protein to cells or inhibit antibodies from binding to it. In this commentary, we have simplified the complexity of the nomenclature of variants related to COVID-19, concentrating on the Delta variant including its transmissibility, response to vaccines, and prevention.


INTRODUCTION
Coronavirus disease (COVID-19) has had a detrimental outcome on the global population and has caused millions of deaths worldwide. In addition, COVID-19 appears to the leading world health crisis since the influenza pandemic of 1918. 1 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has undergone numerous mutations since its initial identification, leading to challenges in controlling the pandemic. 2 So far, several variants have been of concern. The Alpha(B.1.1.7) variant was identified in United Kingdom in late December 2020, Beta(B.1.351) variant in South Africa in December 2020, and Gamma (P.1) variant in Brazil in early January 2021. The Delta(B.1.617.2) variant was first reported in India in December 2020 and is currently the most dreaded variant owing to its enhanced transmissibility and increased virulence. 3 In this commentary, we simplify the complex nomenclature of COVID-19-causing viral variants.
We have also focused on the Delta variant including its transmissibility, response to vaccines, and prevention.

REASONS FOR MUTATIONS
Viruses, especially those with ribonucleic acid as their genetic material, frequently mutate, including SARS-CoV-2 and influenza virus. When a virus is circulating extensively and is causing an illness, the probability of the virus mutating augments. The more chances a virus has to expand, the more it replicates, and more are its chances to undergo changes. An error in this copying process prompts a mutation. Most viral mutations have minimal to no impact on the virus's capability to worsen illness. However, depending on where the mutations are located in the virus's genetic material, they may affect the virus's properties, such as virulence, immune escape, or transmission. 4 It is estimated that SARS-CoV-2 can make more than 1 billion copies (10 9 -10 11 ) of itself after infecting an individual. During this rapid replication, some mistakes occur; these are manifested as mutations inside the genetic material of the virus. 5

SPIKE PROTEIN MUTATIONS
SARS-CoV-2 is covered with fatty membrane proteins (or glycoproteins) that can allow the virus to fuse to the host's cell membrane. The spike protein is located on SARS-CoV-2 shell and is made of a linear chain of approximately 1,300 amino acids. This protein relates to the host cells, such as the pulmonary and parabronchial epithelial cells, 6 and helps the virus enter through the epithelial cell membrane ( Figure 1). SARS-CoV-2 eventually binds with angiotensinconverting enzyme 2, which plays a crucial role in the commencement of COVID-19 infection. 7,8,9 Mutations, which instigate substantial changes in the spike protein, can be of concern because they can induce changes in the biochemical characteristics and structure of the virus. These changes facilitate the spike protein to fuse to cells or inhibit antibodies from binding to it. 10 Selective sweeps in the spike protein, have likely played a crucial role in the adaptive evolution of SARS-CoV-2. 11 Kang et al 11 showed that a single spike protein mutation might be responsible for the transfer of this coronavirus from animals to humans. This study also showed that a single mutation (alanine replacing threonine) was sufficient to allow transmission from bats to humans. Moreover, this replacement led to a simple mutation (T372A) resulting in an easier access of the virus into the human host cell.

CLASSIFICATIONS OF COVID-19 MUTATIONS
In 2020, the World Health Organization (WHO) characterized SARS-CoV-2 variants into variants of interest (VOIs) and variants of concern (VOCs). This classification was aimed at prioritizing worldwide monitoring and research and eventually managing appropriate response to the COVID-19 pandemic. WHO defines a VOI as a SARS-CoV-2 that has phenotypically and genetically changed and can affect the disease relentlessness and community transmission. 12 The current identified VIOs are as follows: Iota  WHO has recommended using the Greek alphabet for VOCs and VOIs to ensure that the labels being used are "easy to pronounce" and "non-stigmatizing" to the countries where they were first identified or are thought to be originating from. 2

NOMENCLATURE OF LINEAGES
There is no collective method to sub-classify viruses below the level of a virus species. Usually, genetic diversity can be sub-classified into distinct clades. These clades may be referred to by a variety of terms, such as "genotypes" or "subtypes" 1to reflect an effort to divide pathogen phylogeny and genetic diversity into their divergent types. 14 The major lineage labels of SARS-CoV-2 begin with a letter, and the current lineages represented are A and B. 14 This system of categorization is proposed only for tracking currently circulating lineages. To demonstrate phylogenetic evidence in a lineage, Rambault et al 15 proposed the following criteria: (1) A new lineage displays one or more mutual nucleotide differences from the ancestral lineage. The most common lineages appearing in the literature start with the letter B, as lineage B has been sequenced and published first (end of 2019). When the sequence of lineage gets too lengthy, the digit "l" is added as an alias to shorten the lineage name. For instance, the VOI spreading in Brazil is known as P.1 rather than B.

PREVENTING NEW VARIANTS FROM EMERGENCE
Halting the spread at the source remains the key. Regularly used precautions employed since the beginning of the pandemic should be strictly followed. These measures include physical distancing, avoiding closed places or crowds, wearing a face mask or face shield, and cleaning hands frequently. By reducing the amount of viral transmissibility, the odds of a new variant emerging are low. Making the COVID-19 vaccine available globally is crucial in ensuring herd immunity. 24

CONCLUSION
The Delta variant (B.1.617.2) is characterized by its increased transmissibility, potential reduced neutralization by sera after vaccination, and possibly decreased neutralization by some EUA monoclonal antibody treatments. By reducing the amount of viral transmissibility, the odds of a new variant emerging are low. Making the COVID-19 vaccine available globally is crucial in ensuring herd immunity.