Explained: COVID Variants & What Makes Them 'Concern'ing

World Health Organization, in collaboration with WHO Virus Evolution Working Group, WHO COVID-19 reference laboratory network, GISAID, Nextstrain and Pango, came up with easy to pronounce and non-stigmatising labels for variants of interest (VOI) and variants of concerns (VOC) using letters of Greek alphabets.

Here's a lowdown on what are variants of concern and variants of interest, which variants have been labelled till now and what is the extent of their spread.

What is Variant of Concern & Variant of Interest?

It is normal for viruses to acquire small changes in their genetic code as they are transmitted from person to person. Often these mutations have no effect. But since these genetic codes provide instructions to make the proteins the virus is built with, occasionally a mutation will alter a protein's structure in such a way that it affects how the virus behaves. Such mutations can give that virus a competitive advantage over related viruses or variants which means the variant becomes the most dominant one over time while infecting the population at large.

Terminologically, variant of concern (VOC) stands is for a strain that is increasingly transmissible as well as virulent or if it is detrimental to bring a change in COVID-19 epidemiology. It could also cause a decrease in effectiveness of public health or social measures taken up on the basis of available diagnostics, vaccines and therapeutics.

"To be considered a variant of concern, it should have three biological properties. If any one of them is different from the previous variants, it could be considered as VOC. Firstly, if the variant is spreading faster than the previous variant. Secondly, if it is more virulent or has caused more severe disease. Thirdly, if it is an immune evader," said T Jacob John, a retired virologist associated with Christian Medical College, Vellore.

Whereas, a variant of interest (VOI) is a strain that's identified to be causing community transmissions or has been detected in multiple countries.

So far, four variants have been labelled as Variants of Concern by the WHO, namely B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta).

Also, there are 7 variants of interest identified by WHO from various parts of the world. These include B.1.427/B.1.429 (Epsilon), P.2 (Zeta), B.1.525 (Eta), P.3 (Theta), B.1.526 (Iota), C.37 (Kappa) and B.1.617 (Lambda).

The US' Centers for Disease Control and Prevention (CDC) has also included a third class of variants called Variant of high consequence. However, till date no variant of high consequence has been identified in the United States. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.427 (Epsilon), B.1.429 (Epsilon) and B.1.617.2 (Delta) are considered as variants of concern by Center for Disease Control and Prevention.

Similar classifications are also made by the European Centre for Disease Prevention and Control (ECDC) where close to 21 SARS-CoV-2 mutants are under monitoring. The Alpha variant was the dominant strain in European Union and European Economic Area among all others.

However, according to the Public Health England, between October 1, 2020 and May 31, 2021, the number of cases and fatalities caused by the Delta variant (94.7%) is higher than the Alpha variant (4.2%).

All Variants of Concern

The Alpha (B.1.1.7) variant was identified in southeastern England in September 2020 and it has spread to the US and other countries. The mutation on the Alpha variant is on the spike protein which helps the virus infect its host. The vaccines make antibodies against many parts of the spike protein.

So, it is likely that a single mutation in the Alpha variant can make the vaccine less effective. This variant was found in over 30 countries. The Oxford-Astrazeneca vaccine was 70.4% effective against the strain while Pfizer is 89.5% effective after 14 days of the second dose. However, it does not escape antibodies from past infection or vaccines.

The Beta (B.1.351) variant was found in South Africa and Nigeria in early October but not publicly announced until December when it was found to be affecting younger people more than the previous variants. This variant appears to be more transmissible than the original SARS-CoV-2 virus.

According to the Centre for Disease Control and Prevention, it is 50% more transmissible and since then has been found in 80 countries. It contains a mutation called E484K and the AstraZeneca vaccine offers only 10% protection from mild to moderate illness caused by the strain. For the Pfizer–BioNTech vaccine, a study conducted in Qatar showed 75% effectiveness. "The effectiveness against any documented infection with the B.1.351 variant was 75%," read the study published in The New England Journal of Medicine.

Gamma (P.1) is seemingly a more contagious and recent strain, the gamma variant started appearing among people from Brazil who travelled to Japan in January 2021. This mutant could infect people who had already had Covid infection in the past and also could evade the antibodies produced by vaccines. People who were infected with the virus before have around 54% to 79% protection against P1.

After the city of Manaus in Brazil was hard hit by Covid in May 2020, it was assumed that the population had gained immunity and developed antibodies for the virus during the first wave. But, P1, which has several mutations in the spike protein the virus uses to attach to and invade a host cell, caused a second wave of deadly infections with higher transmissibility than the previous variants in the area.

"Single booster dose of 50 µg of mRNA-1273 or mRNA-1273.351 increased neutralizing titers against SARS-CoV-2 and two variants of concern (B.1.351, P.1) in previously vaccinated clinical trial participants," read a statement by Moderna on the "positive initial booster data". When it comes to the Johnson & Johnson's vaccine, trial participants produced 3.3 times fewer neutralizing antibodies against the Gamma variant.

The Delta (B.1.617.2) variant was considered to be the primary cause behind India's second wave of Covid-19. As of June 14, 2021, it had spread to 74 countries worldwide and WHO designated the variant as a variant of concern on May 11. This variant rapidly overtook the existing B.1.1.7 (Alpha) mutant in England's Kent and was 43%-90% more transmissible than the pre-existing variant of SARS-CoV-2.

The Delta variant is responsible for 91% of COVID-19 cases in the UK and it is 40% more transmissible than the Alpha variant. Moreover, two weeks after the second dose, Pfizer-BioNTech vaccine appeared to be 79% effective against the Delta variant compared to its 92% protection against the Alpha variant.

According to a study published in the Lancet journal, as compared to those who did not receive any vaccines, those who received the jabs of Pfizer BioNTech vaccine offered protection with 92% in S-gene negative cases and 79% in S-gene positive cases against the Delta variant. And, protection offered by the Oxford AstraZeneca was substantially low with 73% in S-gene negative cases and 60% for those with S-gene positive cases.

Covaxin and Covishield are effective against the Delta variant, said Health Secretary Rajesh Bhushan in a press conference on June 22. Sputnik V is also said to be effective against the Delta variant.

The most recent one is the Delta plus variant with the code B.1.617.2.1/AY.1. It is a variant of Delta and is mostly found in countries of Europe, Asia and America. The difference between Delta and Delta Plus is the K417N mutation in spike protein which the Delta plus variant has.

According to the Centre, as of June 18, 205 Delta Plus cases were detected worldwide, with the USA and the UK reporting more than half of the known cases. Around 40 cases of Delta plus variant were detected in three states of India: Maharashtra, Madhya Pradesh and Kerala. Tamil Nadu and Jammu & Kashmir too reported one case each recently.

On June 22, The Union Ministry of Health & Family Welfare said the Delta plus variant (AY.1) that is labelled as a variant of concern has three characteristics: increased transmissibility, stronger binding to receptors of lung cells and potential reduction in monoclonal antibody response.

"Although at the moment Delta and Delta Plus variants are causing concern but earlier there was a concern in India about the Brazilian variant, P.1. Even the variant Beta found in South Africa raised eye-brows in India since it can be less amenable to certain vaccines and more virulent. But now it does not seem to be too concerning a variant as much as Delta or Delta plus. Necessarily most of these variants could be a little more transmissible but lesser virulence. Shorter incubation period and higher mortality are some of the concerns about the Delta variant," said T Sundararaman, Former Executive Director, National Health Systems Resource Centre.

Not much is known about the effectiveness of vaccines against the Delta Plus variants as it is still emerging. "There is no evidence of widespread escape suggesting that the current generation of vaccines will provide protection against the B.1.617 lineage," according to a study conducted by Oxford University regarding Pfizer BioNTech vaccine.

"While the investigation on the Delta variant is still an ongoing process, we are a long way from complete immunization so the mutations will continue to bring in more COVID-19 waves with slightly different properties of every mutant," concluded Sundararaman.