Updated September 2021
SARS-CoV-2 variants have been identified and studied across the world during the COVID pandemic. To understand the same, let us start by reviewing the coronavirus group.
Coronavirus (CoV) is a family of viruses possessing a single-stranded RNA as the genetic material and is characterized by the presence of spike protein (projecting surface glycoproteins also called S protein). This gives these viruses the distinct appearance of wearing a crown (corona).
TYPES OF CORONAVIRUSES
There are many types (genera) of coronaviruses found in humans (called HCoV) as well as in animals like bats, birds, and pigs. These CoV types are named alpha, beta, gamma and delta. Four species namely the HCoV-229E and HCoV-NL63 (alphacoronavirus), and HCoV-OC43 and HCoV-HKU1 (betacoronavirus) regularly circulate in humans throughout the world and cause the common viral cold.
Coronavirus species found primarily in animals like bats, and not routinely in humans, can sometimes undergo significant mutations (major changes in its genetic material sequencing) and evolve into a new (novel) virus species or subspecies. Research on studying mutations and enhancements in coronaviruses is done in some designated laboratories, with help of animals like humanized mice. Such viruses can ‘jump’ to humans, through animals that people commonly come in contact in wet markets or in and through the research labs.
In 2002, such an occurrence originated in Guangdong, China, and that coronavirus species was called SARS (severe acute respiratory syndrome) virus with the intermediary animals being civets. In 2012, another outbreak happened in the Middle East, where camels were the intermediate animals (MERS -Middle East respiratory syndrome) virus. The coronavirus seen first in Wuhan, Hubei province of China which started infecting humans in December 2019, is also one such novel coronavirus, but no natural intermediary host has been found so far. It was labeled 2019-nCoV, and the disease it causes is called COVID -19. This sub-species has been renamed SARS-CoV-2 in February 2020. All these viruses are betacoronaviruses, where the original and reservoir hosts are bats.
Subtle mutations are seen continuously in coronaviruses as part of the virus striving to improve survival and entry into host cells. Commonly these mutations are seen in the surface spike (S) protein as this enables the virus to enter into the human cells. Over 7000 such mutations have been seen over the course of the pandemic! But a new strain or variant is considered and designated only when the mutation changes the character or behavior of the virus significantly and impacts the disease course and health measures.
New variants have been emerging and evolving through the COVID pandemic and often these strains are designated based on where they were first seen, and the position (number) and type of mutation documented by genome sequencing tests. Lately, these variants have been given simpler names for common use and to avoid country-specific associations. However, these designations of variant strains of SARS-CoV-2 (Alpha, Beta, Gamma, Delta etc.) should not be confused with the types of coronaviruses (alpha, beta, gamma, delta).
Variants of Concern (VOC)
These variants have been seen to significantly impact the pandemic and its resurge (2nd wave) in many parts of the world. VOCs have one or more of the properties of having more transmissibility (spreading more easily), infectivity and virulence (causing more people to fall sick), and immune resistance (making diagnosis, drugs, vaccines and host immunity less effective).
- ALPHA (B.1.1.7) first identified in the UK in September 2020. Designated December 2020.
- BETA (B.1.351) first identified in South Africa in May 2020. Designated December 2020.
- GAMMA (P.1) first identified in Brazil in November 2020. Designated January 2021.
- DELTA (B.1.617.2) first identified in India in October 2020. Designated April-May 2021.
All these VOCs have enhanced transmissibility and infectivity. The Beta strain shows significant resistance while Gamma and Delta strain are showing some resistance. The virulence (ability to cause damage to host) and impact of these variants on disease severity, complications and mortality have still not been fully established.
Variants of Interest (VOI)
The transmissibility, infectivity and resistance, along with impact and role in the resurge and waves of the pandemic of these variants is still being studied, researched and evaluated. Three variants were removed thereafter from the VOI list and designated as ‘variants with alerts’ for further monitoring.
Variants of Interest-
- ETA (B.1.525) seen across multiple countries in December 2020. Designated March 2021.
- IOTA (B.1.526) first identified in New York, USA in November 2020. Designated March 2021.
- KAPPA (B.1.617.1) first identified in India in October 2020. Designated April 2021.
- LAMBDA (B.1.1.1) first identified in Peru in December 2020. Designated June 2021.
- MU (B.1.621) first identified in Columbia in January 2021. Designated August 2021.
Variants with Alerts (formerly VOIs) for further monitoring-
- EPSILON (B.1.427/B.1.429) first identified in California, USA in March 2020.
- ZETA (P.2) first identified in Brazil in April 2020.
- THETA (P.3) first identified in the Philippines in January 2021.
Apart from these there are several other variants from different parts of the world being monitored for their behavior and impact on COVID.
Important mutations in SARS-CoV-2 variants
The N501Y and D614G mutation seen in the Alpha, Beta and Gamma variants confer higher transmissibility and infectivity. The E484K mutation found in the Beta and Gamma variants can reduce the effectiveness of the human immune response. The L452R mutation found in Delta, Kappa and Epsilon variant strain increases viral entry into cells and decreases recognition and response of the human immune system. The Delta variant B.1.617 has both the E484Q and L452R mutations and is sometimes called the “double mutant”.
Some other variants detected in small pockets of India include the B.1.168 in West Bengal with additional D614G mutation, and B.1.36 in South India with N440K mutation (seen to increase viral virulence and disease severity).
A substrain of the DELTA variant, called DELTA plus (also called AY.1 or B.1.617.2.1 variant with an additional spike protein K417N mutation) has also been seen in parts of India and the UK, and is being studied for its higher infectivity, and possible immune escape especially with respect to the available antibody cocktail therapy and vaccines. It has been designated as VOC in India.
So far complete immunization with 2 doses of COVID vaccines confers the most effective possible way of protection against symptomatic especially severe disease, However the measured vaccine efficacy in studies may vary depending on the mutant variant strain.
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