Should we be studying the variants more?
The world is nervously watching the novel coronavirus SARS-CoV-2 and its variants. Every virus sample is technically a new ‘variant’, as its sequence does not match with that of any other virus’ sequence. Each of these variants has the potential to worsen the pandemic or — if the luck favours us — end the pandemic.
When the virus moves from one person to another, it mutates. When multiple mutations come together in a virus, a variant is born. To date, nearly 2 million virus genomes have been studied and more than 1,500 variants have been identified by the Pango Network, a team researchers from University of Edinburgh, University of Oxford, University of Cambridge and University of Sydney.
Out of all these variants circulating the globe, the World Health Organization (WHO) has identified only four variants of concern (VOC), an equal number of variant of interest (VOI) and some variants under monitoring / investigation (VUM / VUI).
The four variants of concern have been named Alpha, Beta, Gamma and Delta. First identified in a sample from India submitted to Global Initiative on Sharing Avian Influenza Data (GISAID) in October 2020, the Delta variant expanded quickly from May 2021 to become the dominant variant globally.
The variant now accounts for 92 per cent sequences being sequenced globally and has been reported from 148 countries.
The Delta variant is one of the three subtypes of the SARS-CoV-2 B.1.617 lineage — namely the B.1.617.2. Researchers have been discovering new information about the variant each day. There are five distinct clades within Delta — clades A to E —and Delta D clade is the most prominent in the current pandemic, according to researchers from a consortium in Israel. They published a SARS-CoV-2 sequencing preprint paper on MedRxiv August 7.
On August 9, nine new sub lineages — AY.4 to AY.12 — were reported, making a total of 12 sub lineages (earlier ones are AY.1, AY.2, AY.3). While AY.4 to AY.11 are predominantly found in the United Kingdom, AY.12 is a sub-lineage detected predominantly in Israel. The researchers anticipate more AY lineages will follow soon.
Delta variant’s genome has 12 mutations (some say that this number is higher), including significant ones in the gene encoding the spike protein. These mutations affect the virus’s transmissibility and whether it can be neutralised by antibodies for previously circulating variants of the virus. Some, like AY.1 or the Delta Plus variant (VOI), are resistant to treatment by monoclonal antibodies.
Some anecdotal pieces claim increased virulence compared to original Wuhan / D614G virus but others do not.
“The Delta variant is more infectious, mainly because the virus output, which is shed into the air, is about three orders of magnitude higher,” said T Jacob John, virologist who was formerly with Christian Medical College, Vellore.
Those who get infected tend to get a thousand times higher inoculum dose, which results in shortened incubation period and increased pathology. “Increased transmissibility means that it also spreads more efficiently from cell to cell in the body of the infected person. That, in turn, means that it is likely to grow to somewhat higher levels, it is likely to cause illness slightly faster, and the illness is slightly more likely to be severe,” said Satyajit Rath, immunologist and visiting professor at Indian Institute of Science Education and Research, Pune.
People infected by Delta test positive more quickly after exposure than if they had been infected by other variants.
The shortened incubation period is a problem when it comes to fighting the infection through the body’s immune response. Symptoms of an infection with the Delta appear to show up in around four days. For the immune system, every day counts.
After infection, T cells and B cells get activated and multiply for several days and then ‘fight’ the virus. If the viral population crosses an important threshold two or three days sooner, the T cells and B cells have a harder challenge on their hands. The vaccines too have been developed keeping the ‘original’ viral strain in mind, where symptoms were visible in around a week.
Such changes in the behaviour make it important that variants are studied in detail as and when identified. Though they are being studied in India too, the number is woefully small, experts say.
“The UK tests every positive sample for full genome analysis. We have set a 5 per cent target but do about 1 per cent only,” said John. Somehow, Indians think of minimalist investment in everything. That is a cultural behaviour — do nothing and all problems slowly dissolve away. If problems do not disappear we learn to be tolerant and live stoically with problems, he said.
The Indian government’s SARS-CoV-2 Genomics Consortium (INSACOG) monitors the genomic variations in the virus through a pan India multi-laboratory network. As of August 16 (according to INSACOG weekly bulletin) has processed 64,460 samples and analysed the sequence of 49,867. To put this in context, a total of 32.25 million people in India have tested positive.
While sequencing number in itself is low, data suggests that the INSACOG is slowly reducing the number of samples studied. For example, in July, only 184 genomes were sequenced down from the 4,381 samples sequenced in June. In May, 13,142 samples were sequenced while in April 15,546 samples were studied. The labs are supposed to test samples collected from sentinel sites, international travellers and special scenarios such as presence of a super spreader or an event like a political rally.
The Integrated Disease Surveillance Programme coordinates sample collection and transportation from the districts / sentinel sites to regional genome sequencing laboratories, where mutations are studied and the information is directly submitted to the Central Surveillance Unit for clinical-epidemiological correlation in coordination with state surveillance officers.
Scientific and clinical advisory group discusses the potential Variants of Interest with experts and if necessary, recommends to the Central Surveillance Unit for further investigation.
The emergence of variants is quite unsurprising what we have known for a long time about viruses and their spread. We do not really seem to have learnt this lesson, given how unsystematically we are still sequencing virus samples, and at the low levels we are doing so, said Rath.
“Virus sequencing can only be done from a fraction of cases due to its cost and complexity,” said Shahid Jameel, a virologist. He, however, pointed out that if done with proper epidemiological sampling, it provides a good view of what is circulating. When it is done at reasonable density, it also provides a view of what is emerging.
“We need to study the variants more diligently and that is done when sequencing is carried out at reasonable density following proper epidemiological sampling,” he said.
We are helpless in controlling the mutations and the emergence of new variants. But this is a matter of grave concern as we know that the steps we took rather effectively against Wuhan/D614G — surgical masks, social distancing, hand hygiene and contact-trace, test, home quarantine, etc are not effective against the Delta variant's transmission. Kerala clearly demonstrates this, said John.
John, however, pointed out that so far all vaccines are effective against the Delta variant. But we are yet to use this solution fully. Only 8 per cent of the country’s population is fully vaccinated as against the needed 50-60 per cent to slow down Delta.
“In the United States, over 95 per cent of hospitalised COVID-19 cases were unvaccinated individuals. If we do not want anyone to die of COVID-19, the uninfected must be vaccinated. If we want to safely open schools all staff and parents should be vaccinated and gradually and increasingly we need to vaccinate children,” said John.
Tedros Adhanom Ghebreyesus, director general, WHO at a media briefing on August 18, 2021, said:
“Delta continues to outpace our collective response, and within each country, hot spots of hospitalisation and death are where there are low levels of vaccination and limited public health measures. We do have solutions to the challenges of Delta and current variants.”
All the past viral respiratory pandemics have lasted two-three years and the same can be expected of COVID-19 too. The virus will lose its virulence and behave just like other common cold coronaviruses that still cause annual surges in young children but without many consequences.
“The virus is still evolving and has got a few more tricks under its sleeve. However, soon it will exhaust all the mutations / substitutions that provide it a higher fitness to transmit between human beings,” said Vipin Vashishtha, national convener of the Advisory Committee on Vaccine and Immunization Practices at Indian Academy of Pediatrics.
“However, it is difficult to predict when this will happen,” he said.
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