#Omicron: 'It's Like Facing A New Bowler For The First Time'

Why is it that we are reacting so adversely? Why is there so much fear as opposed to earlier variations and mutations--of which there have been many? How does this inform our future response? Secondly, many of us are vaccinated, though not at the levels we would like to be. But do these vaccines work?

To understand this well, and to see how thinking can shape public health and public policy response, which becomes very critical in large countries like India, we speak with Dr K. Srinath Reddy, president of the Public Health Foundation of India. Dr Reddy is also an adjunct professor of epidemiology at the Harvard TH Chan School of Public Health, former president of the World Heart Federation, and earlier, the head of cardiology at the All India Institute of Medical Sciences.

Edited excerpts:

Why is it that we are reacting in this way to the discovery of this variant?

I think the fear is because it is now known to be having many spike protein mutations, which will make it much more infectious than the previous versions that we have encountered, including the Delta. The second worry is because there is concern that the vaccines--which have been predominantly directed against the spike protein--are unlikely to be very effective if there are multiple spike protein mutations, which have changed the shape. And the antibodies that have been produced by the spike protein-focused vaccines may not necessarily recognise that spike protein, and hold it down in the bloodstream before it enters the human cells. These are the two main concerns.

The third element we ought to always look at is whether this is a more virulent strain or not, which is likely to create a severe disease. Is it as severe as Delta, more severe than Delta, or less severe than Delta? And even in terms of the immune response to counter the variant, we'll have to try and distinguish between what would have been acquired to a natural infection--where the whole virus would have been exposed to our immune system--as opposed to the vaccines, which have principally presented the spike protein to the body's immune system. So these are some of the unresolved issues.

The concern is because of infectivity, because that's going to overload the health systems. Even if it is relatively mild, we'll be spending a lot of resources in testing and tracing and quarantining and isolating people, even if there are fewer numbers. That means our effort to get back to some semblance of economic and social normalcy is going to be disrupted again. Plus the unknowns in terms of the severity of the infection, and the vaccine efficacy--those are the reasons why people are getting particularly perturbed.

We've seen several variations and mutations in the last 18 months. Weren't some of those also equally infectious, if not more? Delta itself was a more infectious version. And did that fundamentally change anything apart from the fact that obviously it spread faster to more people?

Well, right now, it's very difficult because the numbers are still small. But if you look at what the experience in South Africa and Botswana has been, and also what the experience in Europe, in the Netherlands has been so far, even on the basis of limited numbers, it appears that the speed of transmission is very high indeed. And we have seen not only in the Gauteng province of South Africa, but also including in the sewage samples in Pretoria, where there's a very high viral load. And even in Europe, we are seeing that many cases are emerging with people getting infected.

So the concern is that yes, it is more infectious, because if there are more spike protein mutations, which can firstly evade some of the antibodies that are there in the blood, and more spike proteins can attach themselves to the ACE receptor of the human cells, they can easily prise open the human cells. Also there is some evidence that the amount of viral load in the throat is very high, which suggests a very rapid replication as well. So all of these are pointing towards greater infectivity--not necessarily greater virulence. And that is the area of concern now.

To that extent, should we then treat this as a brand new virus, conceptually, or should we be still treating it as a variation of SARS-CoV-2?

It is indeed a variant, because we know that the viruses will mutate. It's in their nature to mutate. And the reason that they mutate is to continue their existence on earth as a strain or a species. And therefore, there is an evolutionary biology to it. They enter and then initially, they can afford to be fairly virulent, and at the same time, infectious--because there is an unlimited animal or a human host; in this case, the human host. But over a period of time, when people acquire immunity, or people start resisting it with masks, physical distancing, and other methods, or particularly with vaccines which develop immunity, then the virus doesn't have an easy passage. Then, it has to either die down or adapt itself. The way it adapts itself is by increasing its infectivity and reducing its virulence--because if it has more and more limited human hosts to infect, then it cannot afford to exhaust that host; then it writes its own death certificate. So it tends to sort of reduce its virulence, but increase its infectivity. So it is possible that the emergence of this variant is a part of that natural process of evolutionary biology.

But this is hypothetical. We still have to study it in detail, before we conclude, or whether there are still some more steps before that state is achieved, where this virus will learn to coexist with us, infecting some of us, but not really killing many of us.

Many public health professionals and proponents spoke about the state of endemicity that we are entering, or have entered already. Does this new variant mean that we are now retracing our steps or our definition?

Yes, very likely, because the fact that the virus is changing its shape, but it's still amongst us is a sign of endemicity, the fact that it is beginning to adapt itself to changed conditions, because it is being challenged by vaccine-induced immunity, by previously infected persons developing immunity, by people wearing masks. It's not getting an easy passage. So it is adapting itself. It is amongst us and it is endemic, but the endemicity may not be of a particular strain. If we take the virus as a whole, and then we say yes, it is living with us. But in order to become more certain of its continued existence with us, it is changing shape, so that it can become more infectious and at the same time, continue its existence amongst us.

In the best case situation, what could happen given our understanding of how the virus has spread in the past, including earlier this year? And in the worst case situation, what would happen, including the possibility that it may evade vaccine immunity

The best case scenario is that this particular virus is signalling a change towards lower virulence and higher infectivity, which may actually mean that it is on the way to becoming as innocuous as a common cold virus. I'm not saying that it has happened yet, but it could be on that pathway. So in a sense, if this continues in this manner, or continues to mutate to a more infectious but less virulent form further on, then we may actually end up with something like a live attenuated virus vaccine. Even if it infects [us], we'll get immunity and some discomfort, but not lethal disease. That is how it may end up in the best case scenario.

But in the worst case scenario, if it has markedly increased infectivity, immune evasion or immune escape--both to the vaccines and to the natural infection--and also has virulence maintained at the same level as Delta, then we are in for serious trouble.

In India, what's your sense of how Omicron could affect us, given that we have very limited data at this point?

Well, the way I look at it is that we have had, right now, no evidence that it has entered India. But the likelihood is, it will at some point in time, [even] with all the best barriers the viruses will sneak through. All we have to do is to try and ensure that people can protect themselves with masks, with physical distancing, and hygiene, of course, but moving around in ventilated places, and not crowding, so that we don't offer the variant, when it comes in, the same opportunities that we offer to Delta. We sort of gave an open invitation to Delta to come and rampage amongst us. So we have to be careful with that.

Then, we have to also make sure that our surveillance programme is very strong, both at all the entry points into the country, whether it is by air or by sea, or by lab, and try and identify as fast as possible whether the variant has entered at some points in time and then quickly trace the contacts, isolate them. So that surveillance programme has to be extra vigilant in our case. But we also have to study what the behaviour of the virus is. If it is not as virulent, if it is only causing mild disease, then we start reassuring people, but prepare for home care, much more of home care, rather than hospital care. So those are some of the preparations that we need based on the different contingencies. But should it appear to show elements of as severe a virulence as Delta or more, then, of course, we have to really gear up our hospital facilities as well. So those are the kind of contingency preparations that we'll have to make.

Many countries, and even states within India, have announced measures such as institutional quarantine, especially for those arriving from "high-risk" locations--irrespective of vaccination status and negative tests. If vaccines are being treated, from a travel public health point of view, essentially as infructuous, as are seemingly the RT-PCR tests that are being done at the port of departure, what are we really arriving at, in your sense?

Well, I think we are preparing for the worst case scenario with all our defences, and trying to ensure that the virus doesn't sneak through as fast as Delta or other variants emerged, and also make sure that we are giving ourselves time to prepare the systems again, because the systems have started relaxing, thinking that the worst is over and we may not get the third wave. It's like you're facing a new bowler for the first time and you have not had much experience of watching him even in international cricket. So you play defence for a while before you understand his style of play, and then only you open up. So you have to be ultra cautious in the initial stages. And that's what I suppose governments are doing

Many of us have been taking vaccines. There is some discussion about a booster shot. With this new variant, are vaccines effective at all? In the Indian context, particularly, is this time to now speed up or think about the booster shot and will that in itself be a part solution?

As far as vaccines are concerned, the initial promising start, and now a little bit of a doubtful issue, is regarding the vaccines that have been mostly focused against the spike proteins. The world celebrated when the mRNA vaccines came up and said, 'Oh my God, we are focusing on the spike protein, and there's a huge boost in the antibody response much more than we expected, and efficacy rates were 90% plus, up to 95%'. But they, as well as the virus vector vaccines--like for example, AstraZeneca--focused almost exclusively on the spike protein. Now, if the virus develops a number of spike protein mutations, which make it unrecognisable to the antibodies that were developed against the spike protein by the previous vaccines, the virus can easily evade the immune response in the bloodstream and can easily enter the cells where you still have the T lymphocytes and the cellular immunity to fight it off. It's not as though the battle is fully lost. However, the initial defence is broken down. So there is a concern there. On the other hand, the old time-tested inactivated whole virus vaccine--like, for example, Covaxin--might not produce such an effusive antibody response against the spike protein, but it would have had more viral antigens challenging the virus and therefore they may be a broad band immunity, which may be more protective against a variant, which has managed to get a lot of spike protein mutations and evade recognition of the spike protein. We do not know.

I'm sure the National Institute of Virology will do the testing and say how effective this is because they did it against Delta and they said Covaxin was effective against Delta. They also said AstraZeneca also was effective against Delta, a little less so. But the worrying signal has come from Moderna. The CEO of Moderna announced that he expects a substantial decrease in the immuno-protective effect. Of course, the mRNA vaccine manufacturers will say they'll tweak their vaccines against the new spike protein. But this is going to be a game where the virus will keep changing its spike protein configuration, and the vaccine manufacturers will keep changing their vaccines. So I believe it may be safer in the long run to depend upon an inactivated virus vaccine, which provides a whole complement.

The same thing with natural infection. With the natural infection, your body has been presented with a full platter of antigens, and therefore, a person who has been infected with Covid-19 and had a good immune response is more likely to withstand this variant than a person who has received an mRNA vaccine.

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