The TLDR: Over the past month, the daily number of Covid cases have been spiralling in Maharashtra. The Health Ministry has officially acknowledged that the state is beginning its “second wave.” And researchers have flagged the presence of two new mutations in 20% of its hardest hit districts. But are the two linked? Maybe. 

The big surge

Maha numbers: On Tuesday, Maharashtra reported 17,864 new cases—the highest one-day rise for this year—and 87 deaths. Its total number of cases is now 23.4 lakh and overall number of deaths is 52,996. There are 1,38,813 active cases in the state. The worst hit: Pune, followed by Nagpur and Mumbai. There’s been a 60% jump in daily cases in Nagpur. What is also notable: There are a number of new districts—like Amravati, Yavatmal etc—that have entered the worst-hit list for the first time during the pandemic. And of the 19 top districts, 15 are in Maharashtra.

Also spiking: India’s overall number of daily new cases crossed the 26,000-mark on Sunday—for the first time since December 19. But it’s not just Maharashtra. Three other states—Madhya Pradesh, Gujarat, and Punjab—are reporting significant increases, as is Karnataka. Most worrying of the lot: Punjab which recorded 11,942 new cases, and has the highest Case Fatality Rate, i.e the number of cases that lead to death. The current CFR in Punjab is 3.1—which is twice the national average of 1.4. Also worried: Tamil Nadu, which is in the thick of election season.

One key point to note: This is happening in the middle of a massive vaccine rollout:

“And this spike is despite 1.26 million doses of vaccines administered on an average every day in the last week. In fact, India’s inoculation drive is now the world’s second-largest—in terms of daily doses being administered—and is now behind only the US, which is administering 2.5 million doses a day.”

Second key point to note: In mid-February, India’s reproduction number or R-value rose to 1.09—after lingering at .09 since September. R-value measures how many people are infected by one person with Covid. And anything above 1 is worrying. Now, the value has since dropped to 0.6—but these sudden spikes remain worrying.

The big silver lining: Our case fatality rate (CFR)—number of cases that result in death—continues to decline. Even in Maharashtra, it dipped from 1.7% in January to 0.5% in March. This despite a 40% jump in new cases. And it holds true in other states. Example: Karnataka has fallen from 0.7% to 0.3% during the last 5 days.

The four key mutations

Mutations in India: According to experts, around 440 mutations have been detected in the country so far. And this is not exactly surprising since viruses routinely mutate as they spread. But when a virus undergoes significant types of mutations that causes it to behave differently from the original virus, then it becomes a variant. Not all variants have the same significance. As of now, there are only three ‘variants of concern’: UK, South Africa and Brazil—which are all more infectious, and some cause reinfections and/or make vaccines less effective. (For more details on these, see our explainer here)

In mid-February, researchers found two key mutations—E484K and N440K—after genetically analysing samples taken from Amravati and Yavatmal in Maharashtra.

The E484K mutation: is also found in the Brazil and South Africa variants—and is potentially worrying. The mutation strengthens the ability of the virus’ spike protein to bind to the human cell—and it reduces the body’s immune response. Researchers in South Africa and Brazil discovered that it caused reinfections—suggesting that antibodies produced by the first infection by an older variant were ineffective against this one. Also: A study out of New York found that patients infected with that mutation were about six years older on average and more likely to have been hospitalized. 

The N440K mutation: is not new. It was first spotted by researchers in South India—specifically, in samples from Andhra Pradesh in August and September. The significance of this mutation is not clear. A US study showed that it could help the virus dodge the use of a particular ‘monoclonal antibody’—which is a human-made version often used to treat severe cases of Covid. But that may not be a big deal, as The Wire points out:

“The way a virus behaves in a lab doesn’t always translate to how it behaves in an epidemic. Also, even if a mutation may help a virus evade a monoclonal antibody, people may still be able to fight off the virus with other antibodies and components of their immune system, such as T-cells. Additionally the fact that N440K was so common in Andhra Pradesh without causing any noticeable increase in reinfection cases suggests it may not be so concerning, said Anurag Agarwal, director of the Institute of Genomic and Integrative Biology, New Delhi.”

Now, however, a 10-lab research consortium has sounded the alarm over a variant that has two other mutations: E484Q and L452R—and it has been detected in 20% of over 200 genomes sequenced in Maharashtra’s hardest-hit districts. Point to note: this is a double mutation, as in the same virus has both.

The L452R mutation: was found in samples sequenced in California where its frequency increased from 0% in September to over 50% in January—suggesting that it may be more infectious, and is emerging as the dominant variant. Also: An L452R-carrying variant caused the only recorded case of COVID-19 in apes by infecting a gorilla troop at the San Diego Zoo in early January. 

While there is no definitive evidence as yet, a recent University of Washington study found that this mutation again alters the genetic material in the virus’ spike protein that may allow it to enter human cells more easily—and escape antibodies that prevent such binding. Also this: “The findings seem to suggest that the L452R, in and of itself, offers significant adaptive value to the pandemic coronavirus.”

The E484Q mutation: has thus far shown up in 11 countries. And health authorities announced its presence—along with N440K—in Maharashtra, Kerala, and Telangana back in February. But they insisted it was not tied to the surge in cases in these states. But scientists red-flagging the double mutation insist that it can evade antibodies.

The double mutation worry

The bigger issue is the presence of two significant mutations—E484Q and L452R—in a single variant. Scientists have not established a definitive link between this and the surge in Maharashtra. But the double-jump could possibly point to a new, more infectious ‘variant of concern’. A member of the consortium said:

“We’re searching for answers… Are fractions of cases with the double mutation increasing over time? Is the double mutation appearing in clusters of cases? Is it associated with rapid infection spread? Is it causing reinfections in previously infected people?”

And the only way to find these answers is more genome sequencing: 

“Senior epidemiologists have suggested that there is an urgent need to determine who is getting infected in the worst-affected districts. One option would be to simultaneously perform a blood test looking for antibodies while taking throat swabs to diagnose the infection, an epidemiologist said.

 

‘In a large sample, if we find infections without antibodies, we’ll know the virus is spreading only among susceptible people. But if we find the virus in some people with antibodies, we’ll know people previously infected are turning up positive,’ the expert said. ‘We need such studies immediately.’”

The bottomline: In the end, whether there is a new variant of concern in Maharashtra or not, the solution to our rising woes remains the same: masks, social distancing and testing. No, the pandemic is not over yet.

Reading list

The Telegraph has the latest report on the double mutation. New York Times has a brilliant virus variant tracker. Dr Lancelot Pinto has a good, pithy take on how variants affect vaccines in India Today. A very good background read on variants: Our explainer which comes with its own reading list.