Explained | Delta plus variants and what does INSACOG say about them

The labs dedicated to whole genome sequencing say the variants, which are mutations of the Delta strain first found in India, could be more infectious and cause severe COVID-19

The Delta plus variants, known as AY.1 (B.1.617.2.1) and AY.2 (B.1.617.2.2), have now become a new cause of global concern.

These variants, which are mutations of the Delta strain first found in India, could be more infectious and cause more severe COVID-19.

In simple parlance, they are basically the more dangerous cousins of Delta. One variant AY.1 has been declared a variant of concern (VOC) by the Indian government.

How did Delta plus originate?

The Delta variant (B.1.617.2), first identified in India in October 2020, is now the dominant lineage and most of the new samples sequenced in India are now linked to this variant.

The World Health Organization (WHO) has designated Delta as VOC on May 11, 2021.

The Delta variant has multiple mutations. Three of these mutations – E484Q, L452R and P614R – allow the spike protein on the surface of the virus to attach more easily to the ACE2 receptor on human cells.

One mutation is at the furin cleavage site of spike protein, which increases the fitness of the virus in the airway.

Delta Plus variants, which is a new sub-lineage, has an extra mutation called K417N in the spike protein that enhances attachment of the virus to the infected cells.

Among the new sub-lineages occurring within Delta (Delta plus variants), AY.1 and AY.2 are the main new Delta sub-lineages seen in India. They have all the defining seven spike mutations of Delta lineage.

Acquisition of K417N mutation in the Delta (B.1.617.2), which otherwise is a lineage defining mutation for B.1.351 (Beta variant first discovered in South Africa), resulted in evolution of AY.1.

Similarly, acquisition of K417N and A222V mutations in Delta (B.1.617.2), resulted in evolution of AY.2

What are the concerns of the variants?

The SARS-CoV-2 virus is mutating continuously. Mutations help the virus to become either more transmissible or more virulent, or both.

According to US Centers for Diseases Control (CDC), the variants are linked to increased transmissibility, potential reduction in neutralization by some approved monoclonal antibody treatments, and potential reduction in neutralization by post-vaccination sera.

Currently CDC is aggregating Delta plus variants AY.1 and AY.2 with B.1.617.2, but it will continue to evaluate the independent classification of AY.1 and AY.2.

How many cases of Delta plus variants have been reported so far?

So far, 56 cases have been reported from India for a sampling period extending from the last week of March.

AY.1 has been identified in Maharashtra, Tamil Nadu, Telangana, Madhya Pradesh, Kerala, Punjab, Gujarat, Odisha, Andhra Pradesh, Rajasthan, Chandigarh, Jammu, and Karnataka.

AY.2 has been reported in small numbers from Andhra Pradesh, Karnataka and Maharashtra.

The states have been duly notified for appropriate public health actions. So far AY2 has been reported from four countries – Turkey, USA, Portugal and India – but mostly from the USA.

What does INSACOG say about the variants?

Indian SARS-CoV-2 Consortium on Genomics (INSACOG) expects that regions that have already suffered from Delta outbreaks would not have major problems with Delta plus variants, due to reasonable cross-neutralization of AY.1 by antibodies raised against Delta in the population.

As of now, the number of cases with AY.1 infection is not increasing faster than that with Delta. However, INSACOG is keeping a close watch on the situation, since any Delta sub-lineage is a variant of concern meriting further investigation.

INSACOG is made up of 28 laboratories dedicated to whole genome sequencing of the SARS-CoV-2 virus and its evolving variants, and continues to follow the evolution of Delta plus. It is a forum set up under the Ministry of Health and Family Welfare on December 25, 2020, to study and monitor genome sequencing and virus variation of circulating strains of COVID-19 in India.

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