CME INDIA Presentation by Dr S K Gupta, MBBS MD(Med), CFM (France), Senior Consultant Physician, Max Hospital, Delhi.

The Indian Perspective.

A “double mutant” variant of coronavirus has been in India. At present Officials are checking if the variant, where two mutations come together in the same virus, may be more infectious or less affected by vaccines.

HOPE: Mostly it is human behaviour that will drive the second wave. It is our hope that we will make responsible choices.

Nasty mutations in COVID

Five Nasty Mutations of Second Wave, and their properties

1. N501Y Mutation

  • Immune Escape mutation.
  • Could be responsible for reinfection despite Vaccination. Seen in Punjab 324 cases & 75 cases in Delhi. 
  • *N501Y mutation makes variant more transmissible, allowing the virus bind to (ACE2) receptors easily. 
  • Seen in the UK B.1.1.7 variant. N501Y has also appeared convergently in the Brazil (P.1) and South Africa (B.1.351) variants.

2. N440K Mutation

  • Fast transmission but? Mild disease affecting Young.
  • Presently seen in Kerala and Telangana.

3. E484K Mutation

  • Immune Escape mutation.
  • Higher transmission rate.
  • Responsible for reinfection despite Vaccination.
  • Warrants New Vaccine Research.
  • Cases detected in Maharashtra, Gujrat, Kerala.
  • E484K mutation has been seen in South African B.1.351 variant, and in P.1 variant in Brazil. E484K mutation, decreases the neutralizing antibody response produced by vaccines, monoclonal antibody therapies, convalescent plasma, and natural infection.

4. Double mutation E484Q and L452R

  • Seen in Maharashtra but few cased found in Punjab, Delhi and other states.
  • Such [double] mutations confer immune escape and increased infectivity. There may be a separate lineage developing in India with the L452R and E484Q mutations coming together.
  • These mutations have been found in about 15-20 per cent of samples and do not match any previously catalogued variants of concern (VOCs).

5. E484Q mutation and L452 mutation individually

  • Mainly detected in Maharashtra. These mutations have been previously detected in other countries.  E484Q mutation has been found in 11 countries, while L452R mutation has been detected in about 22 countries.
  • Confer immune Escape.

How second wave is different from First Peak?

1. 💹 Steep and Fast Number of New Cases rising faster. Case doubling time in last year was 23 days while this year it is less than 10 days. Last time, in July and August 2020 it took 23 days for India to move from 30,000 cases/day to 60,000. While in this wave just ten days ago, this daily count of cases was less than 30,000. Which jumped to 62000 new cases on 26 March 2021 in less than 10 days . *Cases are rising steeply despite the fact that, society has lesser number of susceptible people because of previous sub clinical exposure, mitigation and vaccination*. Probably number of Vulnerable matter and *Corona seems to spare none*. Complacency in following Covid Appropriate behavior could be the reason.

2. High concentration of cases in a few states is another remarkable feature of this second wave. Maharashtra is contributing more than 60 per cent of the cases every day in Second Wave. While it contributed no more than 22% total cases in previous peak.

Though cases suddenly up 3.7 times in Maharashtra from February levels, they are up 2.9 times in Gujarat, 2.9 times in Andhra Pradesh, 3 times in Madhya Pradesh and 4.9 times in Punjab. But as the baseline number of cases in February were few in these states they are not catching eye.

3. Sequential Second Wave – Gripping states one after the other

Also possible is that different states might peak at different times as already happened earlier. Kerala had been reporting very large number of cases when the rest of the country had fallen silent. When Maharashtra started rising again, Kerala began to decline.

We could see this happening in other states as well. It is possible that Maharashtra begins to show a decline in a few weeks’ time but by then the action might shift to Andhra Pradesh, or Karnataka or Tamil Nadu. Still later, Bihar or Uttar Pradesh or West Bengal might begin their second wave when other states go in a decline. After all people in other more populous states appear to have no special immunity and Corona seems to spare none.

4. Second wave is milder – more transmissible but lesser Mortality Rate.

The weekly case fatality rate for Maharashtra from February 15 to 21 was 0.7%, which declined to 0.32% in the last six days between March 15 and March 20. In the same period, the weekly cases have tripled which might have changed statistics and

it may be too early to say as death rates lag about 2 weeks behind new cases. But Case fatality Rate in Kerala too has been around 0.4% during second wave.

But these are just rates and figures. Total number of human beings dying increase as more population gets affected.

5. How long will it last? Steep rise Fast Wane off Second wave would last for a shorter period of time, though there is no indication that this second wave is coming to an end anytime soon. It could again happen all of a sudden, like last time, when the numbers, rather inexplicably, had begun to come down after reaching 98,000 cases a day.

With more and more people getting vaccinated, and a large proportion having already been infected, the expectation is that the wave should wane off faster than the first.

6. Prediction based on Global Experience

Global Covid-19 experience shows the second wave much higher in intensity than the first wave.

There are models based on European experience that the duration of the second Covid-19 wave might last up to 100 days starting from Feb 15, and the second wave, could last until the end of May. It could see an addition of 25 lakh cases if current trends are taken into consideration.

But Corona seems to be baffling all. Hindsight may not always give correct foresight. Wear Mask and Get Vaccinated.

Refresh Your Knowledge

What is Mutation?

  • Mutation is the property of a virus to undergo changes in its genetic sequence when it multiplies.

What is a Variant?

  • Variant is virus whose genetic sequence differs from its parents.

What is a Strain?

  • It is a variant with (many) mutation(s) which significantly alter its behaviour like Kent (UK) Strain, South African Strain etc

What is Variant of Concern (VoC)?

  • When the changed behaviour of a Strain becomes Cause on Concern for population it is called VoC. Some mutations can even become lethal to virus.

Reading Mutations Names

  • Mutation names denote changes in the virus’s genetic sequence. So, N501Y means the 501st amino acid in the coronavirus’s spike protein has changed from N (asparagine) to Y (tyrosine). Likewise, E484K means the 484th amino acid has changed from E (glutamic acid) to K (lysine).

Why mutations occur?

  • Longer stay of virus in body of (immunocompromised) hosts -allowing multiple replication cycles increases the chances of mutations.

Can we stop mutation of Sars Cov-2 Virus?

  • Since there is no proven anti-viral medication, effective containment strategies like mask, social distancing, early testing, isolation and mass vaccination remain the key.

Second wave in India is due to Mutant Strains or still original Wuhan Virus predominates?

  • Govt is of the opinion that number of cases of variants detected so far, are not enough to attribute second wave to mutant strains. However, as long as enough testing analysis is not done these words may not appear convincing.
  • In wake of second wave in Europe and USA– On 24th Dec 2020 Indian government took initiative of INSACOG, (Indian SARS- CoV-2 Consortium of Genomics) aimed to sequence 5 per cent of all positive cases, to address the concern that India has not been sequencing SARS-CoV-2 isolates to full capacity.

How many samples have been tested?

  • Total of 10787 positive samples have been analysed. It is noteworthy that more than 16 lakh new cases have been added in India since 25th Dec 2020.

How many cases of VoC found?

  • Since INSACOG initiated its working, 771 variants of concerns (VOCs) have been detected in a total of 10787 positive samples shared by States/UTs.

Cases of Mutations so far in India?

  • 736 positives for viruses of the UK (B.1.1.7) lineage.
  • 34 positive South African (B.1.351) lineages.
  • 1 positive for Brazilian (P.1) lineage.

Are mutations confined to one state?

  • No, the samples with these VOCs have been identified in 18 States of the country,”

How can we Control the Second Wave?

  • Balram Bhargava, Director-General ICMR said that COVID-19 tests, masks and vaccination are key to overcome the early second wave.  First wave strategy of Test Treat and Trace remains at the core though.

Which Vaccines are effective against New Strains?

  • “There is an evidence that both vaccines in the country (Covishield and Covaxin) act against both Brazilian and the UK variants too. Research is ongoing about effectiveness of use in South African variants” – Dr Balram Bhargav.
  • mRNA vaccines Pfizer and Moderna not found effective as proportion of neutralizing antibodies dropped 5- to 6-fold against the Brazil variants. And neutralization fell 20- to 44-fold against the South Africa Variant.

CME INDIA Learning Points

  • Double mutant Covid variant has been found in India. An analysis of the samples collected from the western state of Maharashtra showed an increase in the fraction of samples with the E484Q and L452R mutations.
  • The spike protein is the part of the virus that it uses to penetrate human cell. Double mutation in key areas of the virus’s spike protein may allow the virus to escape the immune system.
  • E484Q is similar to E484K – a mutation seen in the B.1.351 (South Africa) and P.1 (Brazil) variants, which have emerged independently several times.
  • Earlier in the pandemic, most spike genes had only one mutation – D614G. Now that mutation is dominant and everywhere.
  • Double mutation (where two mutations come together in the same virus, may be more infectious or less affected by vaccines) is how much doing the havoc in India and bypassing the immune system is yet to be determined.
  • Some virologists are of opinion that India’s new double variant is not likely to be more deadly or more inherently transmissible. But they need more data to confirm this.
  • Mutations in viruses are common. Most of them are insignificant and do not cause any change in its ability to transmit or cause serious infection. Some mutations, like the ones in the UK or South Africa variant lineages, can make the virus more infectious. In some cases, it could be deadlier.

CME INDIA Tail Piece

“Double-variant” had been found in 20% of the cases in Maharashtra, which has seen a huge spike in reported infections. One suspicion is that this variant is the cause of India’s second wave of infections. I would say no, 80% of the samples we have sequenced don’t have this combination of mutants. This mutant has been linked to only 230 cases in Maharashtra of the several thousand samples sequenced.” – Dr Rakesh Mishra, director of the Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) (As told to Soutik Biswas).

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