India failed to predict its devastating second wave. Now scientists say more must be done to prevent a third

Despite general acceptance that a third wave would come from a newly emergent variant, genome sequencing in India has actually declined since the waning of the second wave, as Vishwam Sankaran reports from Chennai

Friday 06 August 2021 12:41 EDT
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Municipal employees work in a disaster management room at their headquarters in Mumbai
Municipal employees work in a disaster management room at their headquarters in Mumbai (AFP via Getty Images)

When reported cases of Covid-19 began rising sharply in parts of the Indian state of Maharashtra in early March, PhD candidate Bani Jolly from the CSIR-Institute of Genomics and Integrative Biology (IGIB) in Delhi began noticing mutations in the novel coronavirus samples from the region.

These were changes in the virus genome that had been reported previously in the context of “antibody escape,” or the ability of the virus to evade the activity of the body’s immune system.

“In March, we found that a lot of the samples we were sequencing had two such mutations. At the same time, other labs from India were also observing that such samples were growing in numbers,” Jolly, whose lab is part of the pan-Indian consortium to monitor the evolution of the novel coronavirus, tells The Independent.

Up until this point, experts, including virologist Shahid Jameel – the former head of the Indian SARS-CoV-2 Consortium on Genomics (INSACOG) – had cautioned that efforts to monitor the evolution of the virus in India were not sufficient to spot concerning new variants before they get out of control.The experts’ fears came true.

By the time the labs could confirm whether this version of the coronavirus, labelled the Delta variant, or B.1.617.2, was truly behind the spike in cases in Maharashtra, it drove a devastating second wave of the pandemic in the country that took nearly 2.5-2.8 million lives in April-May according to some estimates– at least three times the official figure.

Now as the country sees pockets of rising Covid-19 cases, scientists say the intensity and timing of a potential nation-wide wave would be determined by public policy on movement restrictions, people’s adherence to Covid-appropriate behaviour and vaccination, and the emergence of variants of concern.

“During the second wave, all three of these factors were responsible for creating a sharp peak,” epidemiologist Ramanan Laxminarayan tells The Independent, adding that the Delta variant“made a terrible situation worse.”

Since the detection of this lineage, multiple studies have shown that it is more transmissible compared to others, and predominated Covid-19 cases during the disastrous second wave.

“We identified the lineage in March, but now we see that there are sequences which have been identified in late November as well. So there is a possibility Delta could have emerged prior to that,” Sofia Banu, another PhD candidate who is part of the genome sequencing efforts from the Center for Cellular and Molecular Biology (CCMB) in the South Indian city of Hyderabad, tellsThe Independent.

“While we knew that it was important to further investigate this lineage given the significance of the mutations found in it, we did not have in mind that the lineage will grow in proportion as quickly as it did to become the predominant lineage in the world,” Jolly adds.

However, even now the extent of genome sequencing in India is considerably below the rates of virus samples being analysed across the world.

For instance, countries such as Denmark, New Zealand and Australia have uploaded genome data from 40 to 60 per cent its cases in the global database GISAID, while India with over 31 million reported coronavirus infections has so far uploaded sequences of only 0.127 per cent of its cases.

While there were about three to four thousand sequences uploaded to GISAID from India pre-INSACOG, after the formation of the consortium a lot more virus samples have been analysed, and currently there are more than 40,000 sequences on the platform from India alone, explains another scientist who is part of the genome sequencing consortium, and sought to be anonymous for this story.

“But that is still [not enough] from my perspective. I think some labs definitely have the capacity to sequence more if they get more samples. What we are doing is less compared to the sequencing levels happening in the UK where they are able to track every move of the virus,” the researcher adds.

While the consortium initially set goals of scaling up sequencing to assess 5 per cent of positive testing virus samples across the country, Divya Tej Sowpati, another scientist part of the consortium at CCMB says the new strategy over the last two months has been to analyse about 300 samples per state each month, at about 9,000 sequences nationally.

Under this strategy, the government has identified multiple sentinel sites spread across the country to adequately represent the geographic spread of a region, and RT-PCR positive samples are sent from each sentinel site for whole genome sequencing of the virus.

“We tell from our side to the states that it’s okay if they want to send more. So 300 is like the minimum number. But if, if there are some interesting examples, let’s say with a cluster of infections, breakthrough infections, or re-infections, all of those will be collected no matter the number and will be sent,” Sowpati tells The Independent.

However, the rates of virus genome surveillance in India seem to have declined significantly since the waning of the second wave, with only 184 sequences reported in the INSACOG portal for the month of July.

Experts say it can take up to two weeks for samples from a place to be analysed and even more time for any new variant to be flagged for concern – more reason for the country to sequence more samples.

“Only when you put it in context of all other variants you can start saying that this is having a selective advantage, and to get that kind of data we will need to generate data over a period of time to start monitoring it,” Sowpati explains, adding that “it ends up taking some time before we can say with enough confidence that intervention is needed to contain its spread”.

Yet the trend in declining rates of sequencing can still be seen comparing the rates through April and June.

While in April INSACOG reported sequencing 15,546 samples, and 13,142 samples in May, this number came down to 4,381 in June, The Hindu reported on Thursday.

Even though only 184 sequence results have been shared for the month of July, the proportion of Delta variant in these samples has dropped to 73 per cent from being over 85 per cent in samples from May and June.

Meanwhile, while the uncharacterised “others” category of virus lineages made up 13 per cent of overall samples sequenced in June, this section has risen to 26 per cent among the 184 virus genomes analysed in July.

But it remains to be seen if these are hints of a new variant spreading across the population.

As the number of coronavirus infections in the country are rising again, scientists highlight the importance of scaling up testing and surveillance for new variants.

“The surge in cases is certainly worrying. From initially being confined to the single southern state of Kerala and a few, relatively less populated states in the north east of India, case numbers in the southern states of Tamil Nadu, Karnataka and Maharashtra have begun to plateau and even increase slightly, a full month and a half after the peak of the second wave,” Gautam Menon a professor in the departments of physics and biology at Ashoka University, tellsThe Independent.

With only close to 10 per cent of the country’s adults receiving two doses of vaccine, Menon asserts that the need of the hour is for states to accelerate the immunisation drive, targeting the elderly and vulnerable populations first, as well as combating vaccine hesitancy in the over-45 population.

“This is the most immediate course of action they should take. Apart from this, recording cases and deaths better while also stepping up genomic surveillance should certainly be a priority,” he adds.

Considering the current pace of vaccination of about 4.2 million doses per day, which has slightly risen from June’s figures of 3.75 million, experts estimate the country may need to more than double its current rate to achieve its goal of immunising all adults by the end of the year.

As pointed out by BloombergQuint, while India’s nine major cities received about 23 million doses up to late May, its 114 least developed districts had administered just about the same number of shots to their 176 million citizens, and close to 17 per cent more men were vaccinated during this period than women across the country.

With the potential risk of more infectious and immune-escaping variants emerging, homogenous vaccination coverage is essential as leaving out any section of the population could put the whole country at risk of another wave, says Dr Ashutosh Kumar from the All India Institute of Medical Sciences (AIIMS) in Patna, Bihar.

However, it may also be too early to say if current trends represent an upcoming nationwide third wave, says Sitabhra Sinha, professor of Computational Biology and Theoretical Physics at the Institute of Mathematical Sciences in Chennai.

Sinha, who has been tracking the R value of the pandemic in India – an estimate of the number of people a patient can infect – says while the overall value of this measure has gone above 1 for the first time after 7 May, indicating a surge, “it’s also true that this trend is only just a few days old”.

“For example, last winter there were a few days during which R for India had very briefly gone above 1 (after the first wave ended in September last year). However, thankfully, it subsided back to less than 1 after that and we were spared the second wave. So, we should be careful in reading too much into this,” he tellsThe Independent.

Since a substantial fraction of the population in the populous northern states of India, UP and Bihar have already been infected in the first two waves of the disease, Menon says an India-wide wave could potentially be prevented.

At the same time, people who have recovered from the virus after the second wave could experience waning immunity in a few months that may provide the perfect opportunity for new variants to spread fast and take over, cautions Kumar, whose team recently conducted a yet-to-be peer-reviewed study assessing the rise of the Delta variant.

“What we understand from the structural and functional characteristics of emerging variants is that they are highly efficient, plausibly more transmissible and immune resistant, hence are capable of triggering a subsequent wave as the population level immunity for the previous strains wane,” Kumar says.

And to prevent a nationwide wave due to new variants, Laxminarayan says states should pay attention to their rates of testing, the R value, the fraction of people testing positive across the states – a measure called the test positivity rate (TPR) – and impose movement restrictions “earlier rather than later”.

“The Maharashtra government is following a set of guidelines for lockdowns and relaxations that is a combination of test positivities with other parameters. The important thing is to ensure that health care services are not overwhelmed as we saw during the second wave. That is where being judicious about imposing more stringent conditions is very important,” Menon says.

Experts also pointed out that lockdown strategies still haven’t been updated since the earlier stages of the pandemic, despite the fact that we now know so much more about the important role played by building ventilation in the spread of the disease.

“Recommendations regarding ventilation are a relatively minor component of Indian government advisories - we’re still fixated on washing hands and wearing long-sleeved shirts. This is a mistake,” Menon tweeted on Friday.

“Public parks and spaces are closed in multiple cities and in multiple states, even as most other restrictions have been relaxed, which makes little sense,” he earlier noted in an email to The Independent.

While schools have been closed for over a year, the Ashoka University professor says discussions to reopen them in some parts of the country at the moment are not backed by any evidence assessing the tradeoffs involved.

“It is in general better to open up outdoor, open venues and to take as much business into more open areas as possible. Together with this, one should open up enclosed venues, including theatres, much later, once numbers of cases have dropped significantly along with the TPR,” Menon explains.

According to the professor, there may not be the kind of shortages of oxygen cylinders and hospital and ICU beds that were a feature of the second wave in the current scenario.

“These lessons have been learnt and the required logistics are now in place, following intervention by the Supreme Court,” Menon says, adding that states have also become more transparent with their data following constant pressure from scientists during the previous waves.

“The central government is still lagging, however, in making its data accessible,” he adds.

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