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    India will have another wave, get one dose to as many people as you can, says top virologist

    Synopsis

    "A lot of people were affected by the Delta variant in India. Given that there will be some immunity in the population, it might take longer to come back — I would be looking at August-September. Cases will start rising from now but the big take-off will be later in the year," says Dr Ravindra K Gupta.

    Dr Ravinder GuptaAgencies
    With India emerging out of a lockdown and likely to enter another wave “very soon”, at a country-wide level, the focus must be to limit transmission, he says.
    At the end of May, Dr Ravindra K Gupta, professor of clinical microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Diseases, University of Cambridge, had presciently warned that there were signs that the UK was in the early stages of a third wave of Covid-19.

    Proving him right, on June 19, daily cases in the UK crossed 11,000 in 24 hours for the first time since February, driven by the Delta variant, first detected in India. In the context of the surge of cases, the Indian-origin scientist had said that a single dose of vaccine is not particularly effective against Delta, but Gupta, who is also a member of the New and Emerging Respiratory Virus Threats Advisory Group advising the UK government, says the priority for India should be to get one dose of vaccine to as many people as possible.

    With India emerging out of a lockdown and likely to enter another wave “very soon”, at a country-wide level, the focus must be to limit transmission, he says.

    Gupta is also the co-author of a new paper, currently in preprint, with scientists from INSACOG (Indian SARS-CoV-2 Genomic Consortia) which analysed the emergence of the Delta variant and vaccine breakthrough infections and found that the Delta variant is more transmissible, better able to evade immunity due to previous infection and less sensitive to vaccine-elicited antibodies than Alpha variant.

    On a Zoom call from the UK, he told Indulekha Aravind that he wouldn’t take issue with a 16-week gap between two doses of Astra Zeneca vaccine (called Covishield in India) despite lack of real-world data, except for vulnerable categories who might need to be protected faster. Edited excerpts:

    What do your studies show about the transmissibility of the Delta variant and how effective vaccines are against it?
    The data coming from here (the UK) and other places show it transmits at a 50% faster rate. But, of course, that’s the observed overall effect. Now you have a lot of vaccinated people here in the UK just like how in India there were a lot of people with past infections.

    So that’s why, when we did our modelling study, we showed it is transmitting quicker, also because it’s avoiding any or some of the immunity people have. These are two properties of the virus we need to try and separate because otherwise people will just talk about transmission advantage, which is too simplistic and does not take into account the evolution of the virus against immunity and the vaccines.

    You had said one shot of the vaccine is not particularly effective against Delta. What is the dosage interval you would advise for the Astra Zeneca (AZ) vaccine?
    Yes, the first dose of either vaccine (AZ or Pfizer) is not very good at stopping the Delta variant because the levels of antibodies are not very high, they are just not potent enough. It looks like if you wait longer, for three months, you can get higher antibody levels after the second dose.

    But then you are left unprotected for those two months in between. So the balance of spacing of the doses is partly about how much Covid-19 transmission is happening in the community — if there’s a lot of infection and you are at high risk, you may want to have your doses close together. But if you are in a situation where there’s relative control of the infection and transmission, then you might wait three months because you may get higher levels by waiting. It’s not a simple answer. But if you are in a high-risk group, like the elderly or if you have immune problems, then you should have them closer together.

    India’s latest guidance is a 12-16-week interval.

    What should the gap be here, keeping in mind high transmission and supply constraints?
    As India comes out of lockdown, there’s no doubt transmission is going to restart and India is going to enter another wave very soon because it was never completely under control and vaccination numbers are low. In that scenario, I think it’s better to get one dose to as many people as you can.

    On the individual level you might get better protection (with two doses) but the point is to limit transmission at a country-wide level. We need to know whether one dose of AZ is really enough to stop transmission and that’s really not quite clear yet. My statement about one dose to everybody is based on the assumption that it’s effective in limiting some transmission at least….

    Here, we were saying that one dose of AZ gives only about 30% protection against infection (from Delta variant) and for Pfizer it’s about 50%. The modelling needs to be done on whether 30% is enough of a gain to justify giving one dose — it’s hard to say right now. But I think targeting at-risk people first is important.

    Globally, is there any data on the effectiveness of a 16-week gap between doses?

    Not that I know of. But I wouldn’t worry about 12 weeks vs 16 weeks, to be honest. It’s just not much of a difference.

    Given that we are finding enhanced responses after 12 weeks compared with 3 weeks, I wouldn’t have any problems with a longer gap except obviously for vulnerable people who probably need to be protected quicker.

    You said the third wave is likely to start soon in India. How soon is your estimate?

    A lot of people were affected by the Delta variant in India. Given that there will be some immunity in the population, it might take longer to come back — I would be looking at August-September. Cases will start rising from now but the big take-off will be later in the year.

    But a third wave is inevitable?
    It is, unless the vaccine coverage can get high very quickly.

    With the levels of vaccination in India being low and curbs lifting, how is a third wave likely to play out?
    Although India has low rates of vaccination, the background infection right now with the last Delta wave was pretty high. I

    think we may see a similar trend in India that we are seeing in the UK because actually where India is missing out on vaccines, there should be some immunity from Delta. That may not last very long but for the next six months there should be some effect of the infection so I think the trajectory will probably be quite similar.

    You have spoken about super mutant viruses emerging as more people get vaccinated. Is there a possibility of more variants of concern emerging in India?
    My comments on super mutants was more around how if you allow high levels of infection to continue, then you create the condition for super mutants. Sub-optimal vaccination could be part of that. But because you have got a variant already, this could infect somebody and they could have a chronic infection, as we showed in a paper earlier.

    It’s important to keep reiterating that because people forget that’s how it happens: the more people get infected, the more chronic infections happen, the more variants emerge and variants of variants are going to start emerging soon enough. That’s why we need to keep an eye on this.

    Will a booster dose be necessary later?
    I think they will inevitably be needed, partly to increase responses but also to deal with new variants. I think booster doses should start to consist of viruses that are representing new variants.

    The current vaccines will only be useful for so long. You can see the Delta variant is already escaping quite a lot so it’s going to get worse. This is not the end of it, so we need to plan ahead.

    What’s the most concerning factor about the pandemic, after all these months?
    What’s difficult to predict is how the virus can change. It’s already surprised us in many ways. I think that we keep an eye on it for a lot longer than we anticipated. This may be a longer game than we expected.

    That, and the vaccine inequity. The global economy and global travel are critical — the issue is about getting more vaccines to more people so that exchange and travel can restart. Restarting the global economy right now is difficult with the many different restrictions in different countries which are stifling any economic activity.


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    ( Originally published on Jun 26, 2021 )
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