The Delta variant of Covid-19, first found in India, rapidly spread across the world this summer, emerging as the dominant variant globally. But as it mutates further, it has now branched out into the AY sub-lineages, which have gradually started replacing the parent variant.

In the United Kingdom, where Covid-19 cases are on the rise, most samples sequenced recently have shown the presence of AY.4.2. What has caused some alarm is that this sub-lineage is 10-15% more transmissible than Delta and has mutations that help the virus evade an immune response in a previously infected or vaccinated person.

Genome sequencing in India, too, has shown a growing presence of Delta’s sub-lineages. Cumulative sequencing data till October 25 shows 5.7% of 1.07 lakh samples sequenced in India belong to AY sub-lineages. Until September end, AY lineage accounted for 3.4% of total sequenced samples.

In Maharashtra, where over 19,000 samples have been sequenced till October 25, available monthly data of variants shows the percentage of samples with the Delta variant shrunk from 73% in May to 68% in September. In the same period, the presence of AY sub-lineages rose from 13% to nearly 20% amongst all the variants.

The most common sub-lineages of Delta found in India are AY.33 and AY.4, data from Indian SARS-CoV-2 Genomics Consortium shows. Despite higher transmissibility, AY.4.2 – common in UK – has not spread through the Indian population yet.

This has made experts hopeful that India will remain untouched by a nationwide third wave. “At least for the next several weeks,” said virologist Dr Gagandeep Kang, a professor at Christian Medical College.

The main reason for this optimism is that India’s brutal second wave left a large section of its population exposed to the Delta variant. In Mumbai, genome sequencing done by its municipal corporation found that 54% of 343 samples of Covid-19 patients in August and September had Delta and 34% had Delta sub-lineages. A sero-prevalence study in Delhi after September 24 found 97% of its population had Covid-19 antibodies, suggesting a high level of immunity to the virus.

In addition, India has delivered two doses of the Covid-19 vaccine to 32% of its adult population and one dose to 76%. “The good news is that vaccination seems to work on Delta and its derivatives,” Kang said.

Some experts believe that only if a variant which evades an immune response begins to spread in India, does the country need to worry. However, this does not rule out localised outbreaks, which can continue to occur.

Why Delta turned dominant

Mutations in SARS-CoV-2 virus began to surface in the early stages of the pandemic. The World Health Organisation began tracking their evolution from January 2020 itself.

Most mutations were harmless. It was only in late 2020 that variants of concern started emerging. Apart from Delta, these were Alpha (B.1.1.7), first documented in the United Kingdom in September 2020; Beta (B.1.351), reported from South Africa in May 2020; and Gamma (P.1), detected in Brazil in November 2020.

In India, the Delta variant (B.1.617.2), twice as contagious as other variants, was first detected in October 2020. But it was only after two districts of Maharashtra saw an abnormal jump in cases in February 2021 that the government took note of it. By April, Delta had spread to most states, causing a staggering surge of Covid-19 cases that overwhelmed hospitals in many places. Lack of access to medical care further pushed up fatality rates.

Some experts, however, say one of the reasons Delta spread rapidly in India is its ability to replicate faster while at the same time not causing more severe outcomes in patients. “More virulent ones will not propagate fast since they will kill the host body,” epidemiologist Dr Srinath Reddy explained. “A virus will strive to perpetuate its species. It will have an advantage of lasting long in the human population, if it is more transmissible and less severe. Delta matches this description,” he said.

The bulk of Covid-19 samples sequenced by the 28 laboratories that are part of INSACOG, an initiative by the Indian government to monitor genetic variations in the coronavirus, show infection by the Delta variant. Of the one lakh-plus Covid-19 samples sequenced in India till October 25, as many as 43,542 samples showed a variant of concern or variant of interest. Of them 27,409 had the Delta variant and 6,230 had Delta sub-lineages, accounting for 77% of all samples with variants. The Alpha variant was found in 4,232 samples. There were only 219 samples that had the Beta variant, which has a higher potential of escaping immune response.

INSACOG data also shows Delta sub-lineages are gradually increasing in share. Across India in September, 17% of variants had AY lineage, up from 12% in May. But 72% samples in September remain Delta, indicating it continues to be dominant as of now.

In Maharashtra, the most common Delta sub-lineage is AY.33. From INSACOG data available for 1,474 sequenced samples in September, 14% were AY.33. In Tamil Nadu too, the AY.33 variant has grown from 17% to 50% between May and August and Delta has shrunk from 45% to 26% in the same period, although the total sample size is small and only few hundred samples are sequenced every month in the state.

In Kerala, where 6,962 samples have been sequenced till October 25, the AY lineage rose from from 9% to 16% of variants sequenced between May and September. INSACOG data shows AY.33 is the most common Delta sub-lineage in the state.

West Bengal, Karnataka, Telangana have also seen a similar rise in Delta sub-lineages. However, in Madhya Pradesh, Uttar Pradesh, Punjab, Odisha, where sample collection for sequencing remains low – ranging below 3,000 cumulatively – Delta continues to remain the dominant variant.

Travellers wait to get tested for Covid-19 at a railway station in Mumbai on October 9. Photo: Kunal Patil/ PTI

What we know about Delta sub-lineages

Experts say Delta and its derivatives have similar transmission patterns and virulence. Vaccines seem to work on them. “Both the Delta variant and the Delta derivative are relatively mildly invasive and do not pose a significant risk,” the genome sequencing report by Mumbai’s municipal corporation observed. The findings prompted the city authorities to inform the Bombay High Court on October 4 that they do not anticipate a third wave to hit Mumbai.

Countries like China, New Zealand, which saw a fresh surge in October, and Singapore, Russia, that reported a rise in Covid-19 cases since September, attributed the spike to Delta variant. But Dr Hemant Deshmukh, dean in KEM hospital, Mumbai, said the Delta variant is of little concern in India because a large population was exposed to it during the second wave. “We are seeing deaths only in a highly comorbid population,” he said.

However, Dr Rajesh Pandey, a scientist with CSIR Institute of Genomics and Integrative Biology expressed caution against Delta’s sub-lineages. “We don’t know at this point whether or not any of those derivatives end up being of concern,” he said.

According to the Israel health ministry, the AY.4.2 sub-lineage of Delta is 15% more transmissible than the Delta variant. So far, UK, US, Russia, Israel, parts of Europe and Asia have reported AY.4.2.

One of the mutations in AY.4.2 is K417N, also found in the Beta variant, which helps the virus evade immune response and infect a person. Another mutation, A1711V, helps in viral replication. Two other mutations, Y145H and A222V, are in the spike proteins of the virus, making its entry into the host cell easier.

In India, a few cases of AY.4.2 have been recorded. Out of 30 positive cases in Army cantonment in Indore, seven tested for AY.4.2 variant. Chief medical officer Dr BS Saitya told that all infected people had mild symptoms.

Maharashtra, Karnataka, Andhra Pradesh, Kerala, Telangana, Jammu and Kashmir have also reported AY.4.2 but not recorded a significant jump like UK did in the past few weeks.

Dr Anurag Agrawal, director of the CSIR Institute of Genomics and Integrative Biology, said there is no current cause of concern with AY.4.2 and the “risk seems overstated”, at least for India. Dr Pandey of the same institute said they are closely monitoring its spread. “No red signal yet. Unless we see a substantial increase in the percentage of cases, there is no need to worry,” he said.

On October 26, addressing a press conference in New Delhi, health minister Mansukh Mandaviya said experts within the government are examining the risk posed by AY.4.2, but declined to comment further.

Important to continue surveillance

Virologist Kang said India needs to continue its surveillance and closely monitor upcoming variants. Vaccination will reduce viral transmission speed thereby slowing its evolution, but not completely stop it, which means variants will keep turning up in future.

“We first saw alpha six months before it became a problem, we also saw Delta six months before it started spreading fast,” she said. “India’s genome surveillance has improved but we need a serious effort to link epidemiological and genomic data to preempt whether an upcoming variant can spread.”

Although they are unwilling to put a timeline to this, most experts believe the virus will become endemic soon, which means there will be regular localised and seasonal outbreaks, just like H1N1 and dengue. The future waves of Covid-19 will be localised, with small peaks. Kang said before that point is reached, drawing a constant correlation between epidemiological, genomic, and clinical data will provide a safe passage to countries.

Epidemiologist Reddy said,“Unless a major variant comes, the future will see a milder form of Covid-19 coexist with humans.”

Reddy explained that once the Delta variant hits a barrier in the form of the total vaccinated population, the virus will mutate to escape immune response in order to survive. He predicted that newer variants will be milder. “See H1N1 for instance. In 1919, it killed millions, but when it made a comeback in 2009 it didn’t kill as many people. Even coronaviruses will strive to settle down in the human population,” he said.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.