Updated March 2023
SARS-CoV-2 variants have been identified and studied across the world during the COVID pandemic in the last 3 years.
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 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 required.
New variants and subvariants have been emerging and evolving through the COVID pandemic and often these strains were designated based on where they were first seen, and the position (number) and type of mutation documented by genome sequencing tests. However, 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 show 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 the diagnosis, treatment with drugs, prevention with vaccines, and the host immunity less effective).
The Omicron variant was initially called NU and then BA.1. It was first identified in South Africa and designated in November 2021.
The Omicron strain is the most recent COVID variant circulating globally from Nov 2021 till date and has the features below:
- It has more than 50 mutations with around 30 of them in the spike protein (as compared to the mutations in past VOC: 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 past 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 less common.
- Though this variant seems to have less intensity than the past VOC seen in 2020-21, the relative effectiveness of vaccines is still being determined, and updated vaccines are being made available in some countries. However, vaccination continues to be the most recommended protection against all variant strains.
- Omicron can be detected by RT-PCR by S gene drop-out, and is typed by genome sequencing.
Omicron strain has shown further variants (sub-variants) in 2022. The variant BA.2 soon replaced BA.1 as the dominant strain globally in 2022. Other sub-variants that subsequently emerged were BA.3, BA.4, and BA.5.
BA.2 has continued mutating and many of its sub-lineages are under monitoring, like BA.2.3.20, BA.2.75 and BJ.1. The sub-lineage BA.2.75 spread in many countries including India. All these sub-lineages are still being studied for their infectivity and immune escape.
In January 2022, BA.3 variant was also found in South Africa but that showed fewer mutations than BA.1 and is likely less infective or transmissible. BA.4 and BA.5 variants detected in South Africa in April 2022, and now in many other parts of the world including the USA, EU, UK, and India, are also being tracked by the WHO. Sub-lineages of BA.4 (BA.4.6), and BA.5 (BF.7 and BQ.1), are under monitoring by WHO. BQ.1 is now dominant in USA and was also detected in India.
BF.7, (BA.184.108.40.206 – a sub-lineage of the Omicron sub-lineage BA.5) was detected in October 2022 in China and is currently driving the wave there. BF.7 has also now been detected in India and is spreading in the EU and USA. The symptoms are similar to the original Omicron strain, however, the infectivity and transmission are very high for BF.7, and current vaccines are unlikely to confer adequate protection against it.
These have also been seen in 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 the 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.
A recombinant of BA.2.75 and BJ.1 called XBB is currently being seen across many countries. It’s subvariant XBB 1.5 is being considered the most transmissible variant till now and as of 2023 is seen spreading across almost 30 countries globally, including USA, UK, and India. Another sub-variant XBB 1.16 is being seen causing a spike in COVID cases in some parts of India starting March 2023.
While all these variants may be more transmissible than the original Omicron strain, these have not been confirmed to cause more severe disease or complications. Currently, VOC include Omicron BA.1, BA.2, BA.3, BA.4, BA.5 and BA.1/BA.2 circulating recombinant forms such as XE. New variants BF.7, BQ.1, BA.2.75, BA.4.6 and XBB are the Omicron subvariants under close monitoring.
- 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 significant immune resistance, while Gamma and Delta strains displayed some immune resistance. The virulence (ability to cause damage to the 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 spreading in many parts of the world.
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 VOI 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 (FMV) –
- 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 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 was only a limited epidemic that burnt itself out eventually.
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.
As a whole, Omicron subvariants have a high number of mutations in the spike gene (40 in BA. 1, and 31 in BA. 2), of which some were found in other past VOC: Alpha (10x), Beta (11x), Gamma (12x), and Delta (9x). XBB.1.5 has a mutation known as F486P, which restores ability to bind to cells while continuing to evade immunity
So far complete immunization with 2 doses of COVID vaccines (with 3rd precautionary/booster dose also available), 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 THEIR 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 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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I could not refrain from commenting. Well written!