Delta Plus vs Delta variant: How much do we know about these ‘Variants of Concern’?

So far, 50 Delta Plus cases and four deaths have been found across 11 states. Will it be even more virulent than the Delta variant?

According to experts, a mutant variant of SARS-Cov-2, B.1.617.2 — now named Delta variant — was a major reason that led to the devastating second wave across the country. First identified in October in India,  it is now the dominant variant in the country, responsible for 80% of new cases. “It travelled from south to north along the western states — from Kerala to Kashmir, before spreading to the central and eastern states,” says Dr N K Arora, chairman of the COVID working group under the National Technical Advisory Group on Immunization (NTAGI).

The Delta variant has mutations in its spike protein, which makes it more transmissible and evade the body’s immune response. Studies have revealed that it is 40-60% more transmissible than the B.1.1.7 (alpha) variant and has already spread to over 90 countries across the globe. Besides causing the severe wave here, it is now reportedly spreading fast in the UK, in some states in the USA, Singapore and southern China.

In the UK, it is today the dominant variant, accounting for over 96% of new infections. The sudden surge in cases forced British Prime Minister Boris Johnson to delay the lifting of restrictions by four weeks. The variant also caused Israel and Australia to reimpose restrictions. The WHO has warned that the variant is infecting people in 14 African countries, including Uganda and the Democratic Republic of Congo. In the US, Delta’s prevalence almost tripled as Alpha’s dropped by about one-fourth.

Read more: From HCQ to Remdesivir to 2DG: Why COVID-19 treatment is likely to continue evolving

So what makes this variant so transmissible? Experts say though the complete mechanism of its high transmissibility is not yet fully understood, the prevailing hypothesis is that this is because of the presence of two of the nine mutations on its receptor-binding domain region — spike protein — which helps it bind to the ACE2 receptors present on the epithelial lining of the human respiratory tract much more firmly than other variants.

Another Delta mutation promotes syncytium formation (fusion of infected cells with neighbouring cells leading to the formation of multi-nucleate enlarged cells). So once this mutation invades a human cell, it replicates faster than its predecessors, leading to a stronger cytokine storm — chemicals released by the body’s defence mechanism in response to infection. Cytokine storm leads to severe inflammation in organs like the lungs, which can impair their functioning and may be fatal in some cases.

“The Delta variant typically binds to the ACE2 receptors in the lungs, heart and the kidneys cells,” says Niraj Kumar, a bioinformatician, who runs Phynatomics Technology, a company that does genome data analysis.

The other Delta variant

Now, another variant that is fast becoming a variant of concern is the Delta Plus variant. So far, 50 Delta Plus cases have been found across 11 states, including Maharashtra, Tamil Nadu and Madhya Pradesh. First identified on June 11th, a total of 50 cases and four deaths reported have been due to this new variant. This variant, experts say, does not seem to spread very fast. However, the variant is still being studied for its transmissibility, virulence and vaccine-escape characteristics. 

SII's Colvishield vaccine
Scientists at the SII facility working on the COVID-19 vaccine. Pic: Press Information of Bureau

“The Delta variant developed additional mutations of possible importance, so it has been named Delta Plus,” says Dr Anurag Agrawal, Director, Institute of Genomics and Integrative Biology. “Delta plus has K417N mutation, which was also found in Beta and Gamma variants, and is of concern,” he says.  This virus lineage is represented as AY.1 or AY.2.  

A viral variant like Delta causes an outbreak by infecting the vulnerable and those most exposed to COVID-infected individuals in a region and soon spreads like a chain reaction. People who get the infection and recover develop some degree of natural immunity against this virus. When more and more people develop antibodies against the virus, whether through natural infection or vaccination, the number of cases come down. After some time, when this immunity fades or the virus evolves, it can strike and start spreading again.

Currently, different regions in the country are in different phases of different waves, say experts. For example, in Delhi, it was not the second wave, but the fourth wave. The capital witnessed its first wave in June last year, second in September, followed by a third in November, and the fourth in April-May this year.

Know the mutants of interest and concern

Alpha variant: The B.1.1.7. First identified: Kent, the UK
Beta variant:  B.1.351 First Identified: South Africa
Delta variant: B.1.617.2 First identified:  India
Gamma variant : P.1 First identified: Brazil
Kappa variant: B.1.617.1 First identified: India
Delta Plus: AY.1 and AY.2  First identified: Europe

Delta Plus: Will the vaccines work?

Whether the vaccines currently available are effective against Delta variants is a matter of investigation across the world. Various independent studies have shown that the Delta variant considerably reduces the vaccines’ neutralising capabilities. At the same time, scientists believe that overall, the current vaccines are effective in preventing severe disease or hospitalisation.

Experts feel that since the Delta variant has infected a major proportion of India’s population, this is the time to prepare for a future wave. The first step in that direction is to vaccinate the maximum number of people.

Then, there is a need to keep a vigil on the emergence of  variants of concern and outbreaks so that they can be contained before they spread to a larger population. The Indian SARS-CoV-2 Genomics Consortium (INSACOG), a consortium of 28 laboratories (10 core laboratories including ICMR, DBT and CSIR labs and 18 other laboratories across the country), has been set up for genomic surveillance of SARS-CoV-2. It correlates Whole Genomics Sequencing (WGS) data with clinical and epidemiological data to see whether or not a variant is more transmissible, whether it causes more severe disease, escaping immunity or causing breakthrough infections, whether it affects vaccine efficacy and can be diagnosed by current diagnostic tests.

Read more: Attack of the mutants: Will Sputnik help us in our COVID fight?

“This data is being analysed by the National Centre for Disease Control (NCDC). The country has been divided into geographical regions and each lab is given the responsibility of one particular region. “We have formed 180-190 clusters, with around four districts in each cluster,” says Dr Arora, who is also co-chair of INSACOG. “Nasal and throat swabs samples from patients with severe illness or vaccine breakthrough infections, long haulers and with other atypical clinical presentations are collected at health facilities. Besides, regular random sampling is also done, with all these samples are sent to regional laboratories for sequencing. Currently the country has the capacity to sequence around 50,000 sample per month. It takes a week to sequence a batch of sample.”

Though there is a dip in the number of positive cases in most part of the country, regions witnessing a high Test Positivity Rate are largely in the eastern parts of the country, reportedly due to the Delta Variant. “As most of these outbreaks are in the central and eastern regions of the country, it shows how the Delta variant is travelling eastwards,” says Dr Arora.

He insists that COVID-appropriate behaviour continues to be an effective shield against all variants, till a substantial part of our population gets vaccinated. “It is unfortunate that people seem to have forgotten so soon the devastation the virus caused recently,” says Dr Arora. “People need to understand that not following COVID-appropriate behaviour and exposing yourself to the virus means giving it an opportunity to replicate and mutate.  If the virus mutates to evade immunity, there could certainly be another wave.”

SOP for testing and follow up on variants

1. The Integrated Disease Surveillance Project (IDSP) coordinates sample collection and transportation from the districts/sentinel sites to Regional Genome Sequencing Laboratories (RGSL).  The RGSLs are responsible for genome sequencing and identification of Variants of Concerns(VOC)/Variants of Interest(VOI), Potential Variants of Interest and other mutations. Information on VOC/VOI is directly submitted to the Central Surveillance Unit for clinical-epidemiological correlation in coordination with State Surveillance Officers. The samples are then sent to the designated bio banks.

2. RGSLs, upon identification of a genomic mutation which could be of public health relevance, submit the same to Scientific and Clinical Advisory Group (SCAG).  SCAG thereafter discusses the Potential Variants of Interest and other mutations with experts and if necessary, recommends to the Central Surveillance Unit for further investigation.

3. Sharing of information and clinical-epidemiological correlation is done by IDSP, a unit of NCDC, along with the Ministry of Health, the Indian Council for Medical Research, Department of Biotechnology, Council for Scientific and Industrial Research and state authorities.

4. Virus culture, testing for efficacy:  The new mutations/variants of concern are cultured and scientific studies are undertaken to see the impact on infectiousness, virulence, vaccine efficacy and immune escape properties.

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