Updated Aug 2022
SARS-CoV-2 variants have been identified and studied across the world during the COVID pandemic. The COVID virus SARS-CoV-2 belongs to the family of Coronavirus (CoV) which are viruses possessing a single-stranded RNA as the genetic material and 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).
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.
Variants of Concern (VOC)
These variants have been seen to significantly impact the pandemic and its resurge (2nd wave and 3rd wave) in many parts of the world. VOC 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).
It was earlier called NU and now BA.1 and was first identified in South Africa and designated in November 2021. Its variant strain BA.2 which is more transmissible, has now replaced BA.1 as the dominant strain globally.
Since then further mutations have led to more lineages under monitoring (now labeled as VOC-LUM). These include the latest form of BA.2 which is BA.2.12.1 found in some countries like USA. Other variants being tracked as VOC-LUM are BA.3, BA.4, and BA.5, along with BA.1/BA.2 circulating recombinant forms such as XE. BA.5 has recently emerged as one of the prominent strains in USA. While these variants may be more transmissible than the original Omicron strain, these do not cause more severe disease.
- ALPHA (B.1.1.7) was first identified in the UK in September 2020. Designated December 2020.
- BETA (B.1.351) was first identified in South Africa in May 2020. Designated December 2020.
- GAMMA (P.1) was first identified in Brazil in November 2020. Designated January 2021.
- DELTA (B.1.617.2) was first identified in India in October 2020. Designated April-May 2021.
All these VOC have enhanced transmissibility and infectivity. The Beta strain showed a significant while Gamma and Delta strain displayed some immune 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. The Alpha, Beta and Gamma variants are currently spreading at a low rate globally but are being actively monitored. The Delta strain accounted for a large number of cases in the 2nd pandemic wave in India and some other countries, and is still dominant and spreading in many parts of the world.
The Omicron strain is the most recent variant and has the features below:
- It has more than 50 mutations with around 30 of them in the spike protein (as compared to 1 in Alpha, 3 each in Beta and Gamma, and 10 in the Delta variant). This greatly enhances its transmissibility and therefore this variant can spread faster than the other VOC.
- There is a lack of evidence to suggest that it causes increased disease severity, hospitalization, or death.
- So far cases have mostly been mild, with symptoms mainly being irritation or scratchy feeling in the throat, fatigue, and weakness, body ache, low backache, headache, and sometimes symptoms of the common cold. Fever if present is usually low grade. Typical COVID symptoms of loss of smell/taste seen with other variants are usually absent.
- Though this variant seems to have less intensity than the other VOC, the relative effectiveness of vaccines is still being determined. However, vaccination continues to be the most recommended protection against all variant strains.
- It can be detected by RT-PCR by S gene dropout, and is typed by genome sequencing.
- While the original BA.1 has largely been replaced by the more transmissible BA.2 variant, other variants BA.3, BA.4 BA.5 are also being increasingly seen in many countries.
Recombinant variants have been seen since Jan 2022. A recombinant variant occurs when an individual becomes infected with two or more variants at the same time, leading to a mixing of genetic material in the human body. Prominent among these is XE, a combination of BA.1 and BA.2 strains of Omicron detected in UK. Recombinants of Delta and BA.1 (XF and XD) have also been seen in a few cases but not showing community transmission yet. It is still to be ascertained if XE is more virulent, however, it has been estimated to be 10% more transmissible than the BA.2 strain.
The transmissibility, infectivity, and resistance, along with impact and role in the resurge and waves of the pandemic of many other variants were studied, researched, and evaluated as Variants of Interest (VOI) and Variants under Monitoring (VUM).
Currently, no VOIs are recognized.
Previously circulating Variants of Interest (VOI)-
- LAMBDA (C.37) was first identified in Peru in December 2020. Designated June 2021.
- MU (B.1.621) was first identified in Columbia in January 2021. Designated August 2021.
- ETA (B.1.525) was seen across multiple countries in December 2020. Designated March 2021.
- IOTA (B.1.526) was first identified in New York, USA in November 2020. Designated March 2021.
- KAPPA (B.1.617.1) was first identified in India in October 2020. Designated April 2021.
- ZETA (P.2) was first identified in Brazil in April 2020.
- THETA (P.3) was first identified in the Philippines in January 2021.
- EPSILON (B.1.427/B.1.429) was first identified in California, USA in March 2020
Currently there are no Variants under Monitoring (VUM). There were many formerly monitored variants (FMVs)-
- B.1.427, B.1.429 (detected in USA)
- R.1, B.1.1.519, C.36.3, B.1.214.2, B.1.1.523, B.1.619, B.1.620 (detected in multiple countries)
- AV.1 (detected in UK)
- AT.1 (detected in Russia)
- P.2 (detected in Brazil)
- P.3 (detected in Phillipines)
- B.1.466.2 (detected in Indonesia)
- B.1.640 (detected in the multiple countries)
Apart from these, there are several other variants from different parts of the world being monitored for their behavior and impact on COVID. In Jan 2022, a new strain of the COVID-19 causing virus in Southern France, known as ‘IHU’, or B.1.640.2 variant has been reported by researchers in a few cases possibly linked to travel to the African country Cameroon. However, it is too early to speculate on how this variant behaves as far as infection and protection from vaccines are concerned.
Viral mutations are more likely to happen when people with compromised immunity are affected. Both Beta and Omicron variants were first found in individuals with HIV.
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”. The recent Omicron strain has over 50 mutations with over 30 in its spike protein, and some of these mutations are shared with the Delta variant.
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).
Substrains of the Delta variant, called Delta plus are AY.1 or B.1.617.2.1 variant (with an additional spike protein K417N mutation) and more recently AY.4.2 (with the SY145H mutation) have also been seen in parts of India and the UK, and are being studied for their higher infectivity, and possible immune escape especially with respect to the available antibody cocktail therapy and vaccines. The AY.1 was designated as VOC in India, however, the AY.4.2 is yet to be designated either as VOI or VOC.
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.
UNDERSTANDING CORONAVIRUSES AND ITS TYPES
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.
Note- The designations of variant strains of COVID virus SARS-CoV-2 (Alpha, Beta, Gamma, Delta etc.) should not be confused with the types of coronaviruses (alpha, beta, gamma, delta).
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.
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