Delta Is The New Alpha

The questions, as usual, are plenty and never too easy. Is the second wave over? When will the next wave of infections wash up ashore? Will it be as brutal as the previous one? How dangerous is the Delta plus variant? Take that first poser, for instance. The most likely answer: Yes and No. As Balram Bhargava, director general of the Indian Council of Medical Research (ICMR), put it at a press briefing in late June, the epidemic is under control in large parts of the country바카라�about 535 districts at last count바카라�where the test positivity ratio was less than 5 per cent. But not so in some pockets. 바카라�The second wave is not yet over in our country. We still have 75 districts which have more than 10 per cent prevalence,바카라� he said. Averting a future wave, therefore, hinges on a variety of factors바카라�foremost among them being Covid-appropriate behaviour and avoiding mass gatherings.

Even in regions where the two-month lockdowns have been lifted, the threat hasn바카라�t gone바카라�Pune, and other cities in Maharashtra, brought back last week strict curbs such as night curfew from 5 pm and ordered shops selling non-essential items closed during weekends following a state-wide alert on the Delta Plus virus variant that is being closely tracked now. This new variant is from the same family tree as Delta바카라�first identified in India, this one we now know was the primary cause of infection in the country during the second wave.

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But first, a recap바카라�given the difficult technical nomenclature of virus lineages, the WHO in June assigned a simpler naming system of Greek alphabets to the key SARS-CoV-2 virus variants which had so far been commonly referred to by the countries they were detected in. Hence the UK, South Africa, Brazil and India variants became Alpha, Beta, Gamma and Delta. As virologist Shahid Jameel explains it, the variants in circulation in India this year were mostly Alpha and Delta바카라�the other two not having caught on in the country. 바카라�And wherever Alpha and Delta were present together,바카라� says Jameel, 바카라�the former has been replaced by Delta which means Delta is more transmissible than Alpha.바카라� Currently, reports suggest that Delta may be replacing other variants in other parts of the globe as well바카라�it is now the dominant variant in the UK, and several Australian cities have locked down to control the Delta surge there.

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In mid-June, the Indian SARS-CoV-2 Genomics Consortium (INSACOG), a network of genomic sequencing labs that tracks the virus바카라�s spread in the country, began tracking a Delta variant which had a further mutation in its spike protein바카라�this mutation, called K417N, had been previously seen in the Beta lineage and has been associated with immune evasion. The new variant, which goes by the name Delta Plus was first reported by Public Health England in early June but very little is known so far about its clinical relevance. According to INSACOG, the first occurrence in India was detected during a retrospective analysis of a sample collected from Maharashtra in April. Up to this week, about 51 isolates of this variant have been detected in Maharashtra, Kerala, Madhya Pradesh and nine other states. The Delta plus variant has been detected in 12 countries so far.

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Jameel says there바카라�s really no data at the moment to say anything conclusive about the Delta plus. 바카라�Everything that people are talking about is pure speculation. Let바카라�s keep tracking it,,바카라� he says. 바카라�But based on 50 sequences, for people to go out and say it is more infectious or lethal, that it would bring the third wave, that바카라�s all baloney.바카라� Authorities say the samples detected were mostly localised but the alert has been sounded across states and laboratory tests are on to know whether vaccines work against it. 바카라�Whether that virus is going to be significant or not we do not know yet but we have identified where it has suddenly emerged and isolated those people and ring vaccination has been initiated in those areas,바카라� said Bhargava at the briefing.

The bigger worry, Jameel reckons, is people slipping up on precautionary measures as soon as lockdowns ease up. Indeed, cases have dipped바카라�to less than 50,000 new infections this week while vaccination has picked up pace바카라�averaging over 60 lakh most days by the third week of June.

바카라�It바카라�s definitely important to be ready for another wave. But at the same time it바카라�s very hard to predict, no matter how sophisticated the model, that there is going to be a wave because so many things have to come right in order for it to be a nationwide phenomenon,바카라� says Prof Sitabhra Sinha of the Chennai-based Institute of Mathematical Sciences. Even during the first wave last year, he says, there had been localised outbreaks in districts when overall nationwide cases had fallen. Currently, India바카라�s reproductive number (an indicator of the speed of transmission) is around 0.78, which is the lowest it has ever been since the pandemic broke out last year, says Sinha. 바카라�But this is a national average, it won바카라�t tell you much about whether things are going bad in particular states and so on.바카라�

Biostatistician Bhramar Mukherjee of the University of Michigan, who had flagged early trends of the second wave in mid-February, recently told an interviewer: 바카라�I think it is very difficult to predict the timing and magnitude of the third wave at this moment as they depend on virus transmission, human behaviour, virus mutation and level of vaccination. Our models currently do not predict an imminent wave in the next six weeks but the reality can change rapidly.바카라�

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Prof Manindra Agrawal of IIT Kanpur, who is currently working on a projection using a mathematical model called SUTRA, too reckons that predictions of a future wave can바카라�t be made with any certainty. 바카라�The reason is that the characteristics of the virus itself keep changing. One has to just make some reasonable guesses. Effectively, what you can do is create some 바카라�what if바카라� scenarios, they are not really predictions.바카라�

Recently, scientists from ICMR and Imperial College London simulated the potential conditions under which a serious third wave could occur in a mathematical model. Their results suggested that a new immune escape variant would need to fully escape at least 30 per cent of prior immunity, to cause a third wave, and that a more-transmissible variant would need a higher reproductive number of at least 4.5 to cause a third wave. 바카라�Overall, these results suggest that a third wave, if it should occur, is unlikely to be as severe as the second wave, given the extent of spread that has already taken place,바카라� said the paper. 바카라�Consequently, for a virus to cause a major third wave in the face of this pre-existing immunity, extreme scenarios for the abrogation of that immunity are required, or for that matter, for the transmission fitness of any novel virus.바카라�

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Many experts reckon that few places were left untouched by the brutal second wave this summer바카라�a fresh serosurvey, which ICMR has proposed, could point to a clearer estimate of what fraction of the population has been exposed to infection. Epidemiologist Jayaprakash Muliyil says that all the scepticism about the immunity conferred by a previous infection have been proved wrong바카라�meaning that adaptive immunity has been found to be long lasting. It is possible that a more infectious variant can emerge but that, again, means that only people not previously infected are susceptible, he points out. 바카라�We are doing a serosurvey, we바카라�ll wait for the results,바카라� he says.

Currently, the INSACOG network has around 300 sentinel sites from which samples are picked up for genomic sequencing to trace variants. 바카라�We have covered the entire country...all the districts, all the states have been covered,바카라� said Dr Renu Swarup, secretary, department of Biotechnology at the briefing with Balram Bhargava . The sentinel sites include both labs바카라�where transmission can be monitored바카라�and hospitals, where severity of disease can be assessed. The INSACOG puts out a weekly bulletin which goes to the state governments so that immediate action can be taken.

Given the increase in centres and lower caseloads of late, the original target of sequencing 5 per cent of infection cases appears feasible now. But smart sequencing바카라�whereby districts with higher infection rates are targeted바카라�will probably yield better results, says Shahid Jameel. He points to the faster and cheaper genotyping assays being used by Public Health England to identify variants. 바카라�Perhaps some of our labs can deploy that as well to look at Delta plus in a more focused manner,바카라� he says.

Surveillance on all fronts clearly is the way ahead. 바카라�We are rebuilding our capacities in order to analyse up to the taluk and primary health centre-level. And, if there is any trend in positivity picking up in a certain village, to try and adapt micro containment approaches,바카라� says V Ponnuraj, nodal officer of the Karnataka Covid war room. The idea, he says, is to achieve the granularity of PHC- and village-level in Covid management, so that the officers on the ground can take quick decisions and the PHCs can become fulcrum of Covid management, which in turn will strengthen the physical triaging mechanism.

바카라�Whether a third wave comes or not, or whether it will be a wave for the whole country or that different regions will peak and go down at different times remains to be seen,바카라� says Jameel. 바카라�And it will depend on how people are behaving, on how much we are able to vaccinate our population and whether a more infectious variant emerges.바카라�

***

Constant Variables

The fact that the SARS-CoV-2 virus lineages now have easy to use labels says a lot about how common they have become in public discussions바카라�surely B.1.617.2 sounds far more complicated than Delta.

Currently, the WHO lists four Variants of Concern which go by the first four letters of the Greek alphabet. Besides these, are seven Variants of Interest바카라�Epsilon to Lambda.

Since virus naturally mutate바카라�changes to their genetic seq­uence can happen practically every time they replicate inside a host바카라�there바카라�s a constant watch on what바카라�s happening through genomic sequencing and the information is shared via repositories such as GSAID. A virus isolate gets flagged as Variant of Interest when it has genetic markers바카라�like a change in the rec­eptor binding domain바카라�that could potentially affect transmission or immune escape. When there바카라�s evidence of this happening, it becomes a Variant of Concern (Delta, for instance, was designated a VoC on May 11 this year).

As of last week, India had sequenced around 45,000 samples바카라�typically these are picked up from various sites across the country and include samples from international travelers arriving in India, hospitals, testing labs and from high transmission areas. The sampling also looks for repeat infections and infections post vaccination.

So far, the variants with public health importance detected in community samples in India are Alpha (3969), Beta (149) and Gamma (1). The Delta lineage, meanwhile, was found in several states where it drove the surge in cases during the second wave, according to Sujeet Kumar Singh, director, National Centre for Disease Control (NCDC). 

By Ajay Sukumaran in Bangalore