UK, California, Manaus: What they suggest about the Covid crisis in Maharashtra
In the middle of February, when India recorded its lowest Covid-19 numbers in a year, the state of Maharashtra began bucking the trend. The inflection point appears to be right in the middle of the month – on February 14. In the first 14 days, the state logged an average of roughly 2,500 cases a day. In the latter half, this number swelled more than twice to 5,300.
And the rate doubled again over the next fortnight – the first two weeks in March.
For the rest of India, the inflection point would not arrive till March 3. By this time, Maharashtra’s trajectory had begun ringing alarm bells.
Imperfect sampling for serological surveys and whole-genome testing has meant that the government has not been able to determine whether this trend is due to a factor beyond simply people being careless, although it has found an increasing number of samples showing two particular mutations: E484Q and L452R.
The deviation in Maharashtra’s trajectory (and to some extend Punjab’s) resembles examples from three other regions where mutations have in fact been implicated: United Kingdom (UK)’s London and south-east, Brazil’s Manaus and California in the United States (US). All three are believed to be the ground zero for variants that make the coronavirus spread more readily or cheat immunity from a previous infection (or both).
Parallel 1: London and SE England, the UK
All things being equal (in terms of restrictions), Maharashtra’s case trajectory against the backdrop of the rest of the country has a particularly similarity with what happened in the UK at the outset of last winter.
Within a fortnight, beginning November 29, London and parts of UK’s south-east turned into new hotbeds of coronavirus infections. This was particularly stark since the country was in the middle of a lockdown (UK’s lockdowns have typically been less stringent than what Indians are used to) to avoid an expected surge during the Christmas holiday season.
This surge would eventually be attributed to the variant known as B.1.1.7, or VOC 202012/01 – the first coronavirus variant under investigation. The variant has since been correlated with the virus becoming more infective and slightly more lethal.
Parallel 2: California, US
A little over halfway into January, the state of California overtook the New York state to become the hardest hit region in terms of fatalities in the US. What would be its fourth wave, infections in California began surging in the run-up to Christmas for a peak that would last roughly three weeks beginning late December.
To be sure, California is US’s most populous state, but the December-January wave is unique for its magnitude — at one point it was detecting over four times as many cases in a day in December as its second wave in July.
The holiday season has been seen as a clear link. But increasingly, scientists are also suspected a new variant to be causing it. Over five months beginning September, this variant rose to account for more than 50% of all samples subjected to genetic analysis, the LA Times reported.
This variant is known as B.1.427 and B.1.429 and scientists believe that it may be drawing its more worrying nature from the particular mutation that has also been detected in Maharashtra: L452R.
At least two studies, here and here, find that the L452R mutation in particular was more resistant to antibodies drawn from people who had a previous infection with the globally predominant variant or from those that had taken vaccine doses. Both the studies were lab tests, and how this increased resistance translates needs to be verified.
Parallel 3: Manaus, Brazil
The region of Manaus in Brazil has been mysterious for scientists since the end of last year. For roughly seven months from May to November, the city with one of the highest population densities in Brazil reported very few Covid-19 cases, despite considerable relaxation of restrictions.
Researchers estimated that roughly three quarters of the population may have been infected, surpassing the theoretical herd immunity threshold. This partly supported the May-November lull in cases — until the outbreak exploded again.
Researchers now believe there are four possible explanations for the lull and the resurgence — one, that the initial three-fourths attack rate was exaggerated and the population was never this protected; two, the seven-month period is when immunity from the first infection waned to cause re-infections; three, the new outbreak is triggered by a variant that is resistant to antibodies from previous immunity; and lastly, that a new variant that is more transmissible has taken hold.
The strongest suspicion now falls on the variant known as P.1, which has a constellation of mutations including the N501Y from UK’s B.1.1.7 variant and a mutation at the location 484 (known as E484K). N501Y has been linked to the UK variant becoming more infective while E484K has shown to be more resistant to antibodies generated in response to the older virus.
The link with Maharashtra
Similar trends have also been seen in South Africa, where the variant B.1.351 too has E484K mutation. But the examples of UK, US and Brazil have significant overlaps with what has been observed in Maharashtra and what little is known about the virus there.
The London-South-East England and California examples shows a sudden, relentless outbreak can be due to a fitter mutation – the latter case shares a particular mutation that has been found in Maharashtra.
The Manaus example too reinforces the risk from mutations, but it also points to the fact that herd immunity may not translate to any sort of protection in a region such as Maharashtra, which has consistently had high levels of outbreak since the pandemic began in India.
In all three cases, the outbreaks have spread out – driving new surges as the variants travel beyond states and borders.
The lack of data from genomic surveillance means India is unlikely to determine whether Maharashtra’s worsening situation is due to something similar, and the longer that question remains unanswered, the more difficult it becomes to take proactive decisions on measures to tackle it — for Maharashtra itself as well as the rest of the country.
India set up a consortium of labs called INSACOG and targeted genome sequencing of at least 5% of all positive. But since January, a little under 11,000 had been done — this number is short of the at least 48,000 it should have been, based on the 966,376 cases recorded in the country between January 1 and March 23.
Experts have called on the government to increase the whole genome sequencing volumes. What could also help is if the government releases the timeline of the genomes sequenced till now, which determine how proportion of mutation samples change in a region — helping establish at least one proxy for epidemiological estimation.
Determining the threat from variants is key not only to head off the current outbreak, but also to tweak India’s vaccination strategy — including the question whether the government now needs to look at approaching other developers with more immunogenic products.