* This is one among a gazillion new variants that we will see

* We do not need to panic. There are two important things to do — one is sequencing and the other is regular sero surveillance

* We need to be looking to see whether this is going into animals. Because if it is, we may be setting up reservoirs from which this will come back again

* As long as there is low vaccination and high rates of infections in any part of the world, we are all vulnerable to the re-introduction, spread and threat of new variants that may not be protected from by existing vaccines

***

Covid-19 infected over 1 crore people and claimed over 1.5 lakh lives in India in 2020. India not only has one of the world’s highest case loads, but it has also been seeing one of the highest recovery rates — 95 per cent, as opposed to the global average of 70 per cent. Yet, the worst might not be over. The virus has been mutating and one of the most prevalent strains, commonly known as the UK variant, is believed to be 70 per cent more transmissible.

BL ink spoke to clinician scientist and Royal Society Fellow Gagandeep Kang on a spectrum of issues — including what India can do to guard itself against a mutating virus, why we need a one-health approach and whether the Central Drugs Standard Control Organisation’s (CDSCO) recent approval of two vaccines (Covishield and Covaxin) for emergency use is safe given their data efficacy shortfall. Excerpts:

What do we know about the new mutant Covid-19 strain, also known as the UK variant, and in what way is it different from the existing Covid-19 infection?

There are many mutant strains. If we’re talking about the UK variant, N501Y is a particular mutation identified in April 2020, in Brazil. The other 16 mutations have come together with N501Y to form this particular variant that has been in the UK from September onward. From then on it has increased as a proportion of the sequenced strains. Because of the locations of the mutation on the spike protein, the inference is that this is a strain more likely to bind better to the ACE2 receptor. That’s how it gets inside cells. Therefore, this will be a strain that will infect more easily.

The reason this strain is believed to have greater transmissibility is because the strain has essentially taken over from others. It has a growth rate of 70 per cent compared to other variants. Growth rate here refers to growth in infection in a population, not growth of a virus in cell culture.

With SARS-CoV-2, if people mix as they normally do, provided that everybody is equally susceptible, one person will result in spreading the infection to somewhere between 3 and 3.5 people. The reproductive number or R value, without any interventions, is in that range.

If our goal is to stop the infection from growing we want to keep the R value as low as possible, to get it down to 1. An R naught of 1 will mean that the infection will be maintained in the population but it won’t grow. If you want to remove an infection from a population you have to get the R value below 1. For instance, if the R becomes 0.9, that means that if you have 10 infected people, the next generation of infections will only be 9 infected people and the generation after will only be 8.1 infected people and so on. You will ultimately be driving the virus towards extinction if you’ve got your R below 1.

Everything that we do, wearing masks, or maintaining physical distancing is all intended to drive R down. Lockdowns are supposed to make the R zero because you’re not supposed to meet anybody that you can potentially transmit to.

In the new variant, we have no idea what its native R0 or base value is, because we’ve never seen it in a population. But based on the fact that it appears to be more transmissible, it has been calculated that there may be an absolute increase in the R that may be about 0.4.

This matters because if your R is at 1, it now becomes 1.4. This will creep upwards, increasing growth of the infection. So your suppression to keep it below 1 has to be that much stronger.

It sounds as if any progress we’ve made is about to be taken away...

Some progress that we’ve made is being taken away by increased transmissibility, so we need better structured control measures to suppress the virus, and these measures are what we already know about prevention of infection by masking and distancing and vaccines, as well as test, trace and isolate.

Are symptoms and treatments for the new strain the same as the old?

Symptoms are the same and treatments are the same. This is only about transmission and spread. There is no evidence that this is more severe or in any other way more dangerous. Mortality is the same too. The only thing is since it is more infectious, we might see more infections where we haven’t seen them at the same level such as in children.

There are over 70 known people infected with the UK variant in India. Initial studies show that this will affect a younger population more, is that true?

That’s inference. Everybody can potentially be infected with these viruses, but because transmission is high and the viral load is higher, we will see more infections in younger people. We do not need to panic. The only thing this should remind us is that there are two important things to do — one is sequencing and the other is regular sero surveillance. Sequencing allows you to track strains and I’ve worked in virology long enough to understand the importance of molecular epidemiology that acts as an early signal of what’s going to happen. And sero surveillance involves looking for antibodies for the virus so you know how much of the population is already infected and how many people are still at risk of being infected.

If you’re tracking variations all the time, you may be able to quickly pick up when the variations may drive a change in the epidemiology of the virus. Sero surveillance tells you how much of your population has been infected and therefore helps you plan for better strategy. For instance, why bother doing a lockdown in a place that has 70 per cent sero prevalence?

India did a lot of sequencing of viral genomes recently, and then it slowed down based on submissions to the sequence data sharing website, GISAID. With the UK variant, the government is now establishing a network of laboratories and a programme for regular sequencing, which is good for the future of surveillance in India. This virus is going to be around for a while.

In what other ways can we prepare ourselves for a mutating virus?

With RNA viruses there will always be new strains. This is one among a gazillion new variants that we will see. This is not a new thing for viruses. What we need is better sample collection and better sequencing and then we need systems to understand what biological differences will come from sequence data. The time for excitement is when the sequence, clinical and epidemiological and laboratory data all show that the virus and our response are changing.

I actually think that for this virus we need a one-health approach. We need to be looking to see whether this is going into animals. Because if it is, we may be setting up reservoirs from which this will come back again. Given that in India we have a lot of animal-human proximity, we should track viruses both in domestic pets as well as animal herds. So, if you have backyard agriculture, where a lot of animal-human interaction takes place, what you need is a lot of categorisation, representative examples of what is happening in urban and rural areas and sequencing of the samples collected from all these sources. It needs to be a systematic approach.

Earlier this week, the CDSCO approved two vaccines on emergency use — from Bharat biotech and Oxford. In the absence of conclusive data on efficacy how safe is this? Is vaccine nationalism dangerous for India?

Regulators examine quality, safety and efficacy data in order to approve products. The Subject Expert Committee’s minutes provide at least a high-level view of the information based on which they made their decision. In the case of Bharat, since clinical efficacy data are not available, the SEC appears to have relied on the animal data.

In further communication it was stated that the regulator relied on the provision in the New Clinical Trial rules published in 2019, which state [that it can proceed]‘if remarkable efficacy is observed with a defined dose in the Phase II clinical trial of the investigational new drug for the unmet medical needs of serious and life-threatening diseases in the country’.

However, at least in my view, ‘remarkable efficacy’ may be demonstrable in phase II for drugs, but unfortunately not for vaccines. That said, the SEC is composed of experts and they may have had access to more data than mentioned in their committee minutes.

Vaccine nationalism is a threat to global health security because as long as there is low vaccination and high rates of infections in any part of the world, we are all vulnerable to re-introduction, spread and the threat of new variants that may not be protected from by existing vaccines.

The ICMR chief holds that Covaxin was approved as it has been found to be more likely to act against the mutant Covid-19 strain...

It is certainly possible that this may be the case, but there is currently no data.

Based on the government’s existing plan of vaccinating 30 per cent of the population by July, getting the whole country covered could take us into 2022. Anything we can do to speed this up?

I actually think we should vaccinate everybody but I think we should aim for as much as possible. I doubt we’ll achieve more than 70 per cent if we try to vaccinate the country in any time frame. Having said that, I think we are moving pretty fast already and quite frankly, in India, we’re in a fantastic place compared to the rest of the world.

Is there truth in the BCG vaccine giving Indians added immunity in general and particularly resistance to Covid-19? Where do you think our resistance stems from?

There is as much truth in it as there is in the claim that in India we live in unhygienic surroundings so our immune systems are better set up to resist infections. Both are hypotheses and need to be supported by strong evidence.

In the ecological studies, it has been proposed that BCG at any time in the past will protect from SARS-CoV2 infection. For me, it’s very difficult to imagine that BCG effects last 40 to 50 years. There are ongoing trials that are looking at BCG given recently in healthcare workers. And hopefully those trials will tell us whether BCG works.

I’m still looking for explanations for why we’re not seeing more severe disease and higher mortality. And I am unclear about the potential reasons. Is it that we’re not recording all deaths? That may be a proportion. Is it because we don’t have an elderly population? That’s a proportion. But still even with all those, there may be something different about the Indian immune response and it might be that we live in such an inflamed environment, something is always triggering inflammation in us that we are quite tolerant to a virus that comes along and says here’s another little bit of inflammation to add onto what you’re doing.

Each country has a different vaccination strategy. Indonesia, for instance, wants to vaccinate its young and working population first because they’re the ones most exposed to infection compared to the senior citizens who are safer, being isolated indoors. What is the ideal way to prioritise for a country like India?

There is no ideal way. The question is what is the goal of your vaccination plan? If the goal is to prevent morbidity and mortality then vaccinate the elderly and those most at risk, such as people with co-morbidities. If the goal is to prevent or decrease transmission, then vaccinate the people most likely to spread infection, which is your working population and young people.

The latter seems to be what we should do because we want to curtail spread at this point?

I don’t know how the government is going about this, but from what has been reported in the media, I am concerned about plans to vaccinate only proportions of the population. Reliance on herd immunity may be good for public health, but is not necessarily good for the individual, and I worry that those left out of vaccination will be the poorest and most vulnerable.

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