Does the Omicron variant make a case for booster doses?

What is the major objective of a booster dose — to protect from infection or protect from severe disease and death, who should get it first whenever it is approved, is there enough evidence recommending for their use, and should we give boosters when primary immunisation is not complete? Dr. Chandrakant Lahariya, physician epidemiologist and a public policy and health systems expert and immunologist Dr. Satyajit Rath, formerly with the National Institute of Immunology, discuss these issues.

If conversations around booster shots to tackle COVID-19 were loud earlier, the emergence of the new variant, Omicron, has ensured that the clamour for booster shots has reached a fever pitch. The Health Minister stressed that India’s priority is to fully vaccinate all adults and not administer booster shots even though adequate vaccines are available. He also said that any decision on booster doses will be based solely on scientific recommendations.

At a recent meeting, the National Technical Advisory Group on Immunisation maintained that it was not recommending a booster dose for any section of the population, priority groups included, in the absence of evidence. In a conversation with Dr. Chandrakant Lahariya and Dr. Satyajit Rath discuss certain contentious issues surrounding booster doses.

What is the primary objective of a booster dose — to prevent symptomatic infection or to prevent moderate or severe disease and death?

Satyajit Rath: First, let me raise what I suspect is going to be an elephant in the room during this entire discussion. Are we talking about the purpose of vaccination with outcomes at the community level or are we talking about the outcomes of vaccination in terms of protection at the individual level? This is going to remain a point during any discussion about booster shots. The evidence so far is that we are far more efficiently protected against severe illness, hospitalisation and death by being full vaccinated than infection and transmission. The expectation from boosters is that they will proportionately increase protection against infection and transmission. However, the evidence that booster doses do this is fragmentary.

Chandrakant Lahariya: I would approach this in a different way. We know that boosters are being considered globally for a different set of populations. And when we think of the purpose of boosters, we have to go back to the purpose of the COVID-19 immunisation programme. The purpose is to reduce hospitalisation, severe disease and death. Now, that purpose can be achieved through administering full vaccination. So, the booster dose does not have a separate purpose; it is intended to fulfil the overall objective of the COVID-19 vaccination programme. We really do not know whether giving booster shots adds any value to the primary purpose of the immunisation programme.

How much do we know about the effectiveness of Covishield and Covaxin in preventing symptomatic infection and severe disease? In the absence of many studies on vaccine effectiveness, what will be the basis on which a decision on booster doses will be taken?

Chandrakant Lahariya: We know that there is evidence indicating that while the antibody level goes down over a period of time, protection against severe disease and hospitalisation remains unchanged. So, unless we change the purpose of the vaccination programme, which is to reduce symptomatic disease, the need for a booster shot is not going to be altered.

Satyajit Rath: In real-life effectiveness studies, while one can debate endlessly on just how much evidence is enough evidence, I don’t have any difficulty in accepting that both Covaxin and Covishield provide a significant measure of protection against severe illness and death. We don’t have reliable evidence about [protection against] infection and transmission and mild or asymptomatic disease. But none of that gives us evidence for how to decide about a booster dose. Because, if we are looking for protection against hospitalisation, we already have a vaccination campaign that in the first place is not complete, and where vaccines have been administered, we have every expectation that they are going to be effective. So, I’m not certain of what the evidential or the tactical basis for discussing a booster dose inclusion in a vaccination campaign is.

India has administered over 1.26 billion doses, and the vaccination programme has been going on for about 11 months. At this point, should we not have had several effectiveness studies looking at different aspects which should have helped us decide about booster doses?

Satyajit Rath: Certainly. But even if we have data about the effectiveness of two doses of Covishield or Covaxin in preventing hospitalisation and death, how does that tell us whether boosters will work or not? Even if it turns out that we don’t have reasonable protection in real-life circumstances against hospitalisation and death with two doses of the vaccine, that doesn’t automatically tell us that the booster is going to work.

Chandrakant Lahariya: We need to remember that vaccine effectiveness remains unchanged over a period of time against hospitalisation and death. But the bigger point when deciding about a booster dose is: where is the cut-off for saying that this much protection is enough and this is what we want to achieve? Second, how do we decide what level of effective benefit or protection we want to achieve through the booster? Finally, do we have data for these vaccines [used in India] or different vaccines that giving a booster shot will result in improved protection? There is some data that a booster shot of the Pfizer vaccine produces improved protection. But we don’t have that kind of data for other vaccines. So, all these studies should be done, analysed and interpreted in combination with other factors. Only then can a decision be made.

Does the emergence of the Omicron variant make it necessary to administer a booster dose?

Satyajit Rath: The emergence of the new variant makes the case for a global inclusive primary vaccination campaign for COVID-19 even more compelling than it was. Does it separately make a specific case for a booster dose programme more compelling? I don’t think so, for all the reasons discussed so far. You’re going to have a little more transmission and hospitalisation, but protection against that [hospitalisation] is likely to be higher. For booster doses, evidence for protection is scarce. What Omicron does is make the case for primary global inclusive vaccination more compelling rather than specifically increasing the pressure to plan for boosters.

Chandrakant Lahariya: We know that the ability of the available vaccines in reducing transmission is limited. We also know that based on available data, Omicron causes mostly mild disease. Currently licensed vaccines have a proven role in reducing severe disease, hospitalisation and death. So, there is definitely a clear disconnect that because of Omicron there would be any additional advantage in reducing any kind of illness. The focus has to be on ensuring that everyone receives a primary schedule of vaccination. There is no additional value in administering a booster because of the Omicron variant.

Who do you think should be the first to get booster doses — immunocompromised people, people older than 60 years, or those with comorbidities?

Satyajit Rath: We really don’t have good evidence. For example, there is evidence that booster doses increase antibody levels. But do they increase antibody levels in specifically immunocompromised individuals who have not responded well or have not responded for a long duration to the primary vaccine schedule? We don’t know.

Of course, if we had achieved proper universal primary immunisation coverage and if vaccine supplies were available and approved, it would be nice to have boosters available for identified categories of particularly vulnerable people. But no conditionality — the supply conditionality, the primary vaccination campaign success conditionality, or the conditionality of evidence for boosters working in these categories of people are being fulfilled.

Chandrakant Lahariya: The need for a booster can be assessed based on the pattern of breakthrough infections or which population group over a period of time is reporting more severe disease. These would also vary according to the type of vaccine used. So, we need more granular data on epidemiology, disease burden, and breakthrough infections before we identify age groups. This is also true for vaccine-specific data — protection, efficacy, effectiveness, and duration of protection.

Next, we need to know about the performance of booster doses. We need to know that the vaccines perform when booster doses are given to different sets of population. It is not necessary that the protection will be similar in each age group, but we need to know that. We need to know what the optimal timing after the second dose should be — six months, nine months or a year. And whether it should it be a homologous or heterologous booster dose because the majority of countries are giving booster doses using either a different vaccine belonging to the same platform or vaccines from a different platform. We need to explore whether booster doses should be of the same amount of vaccine or a dose-sparing formulation.

Another key factor is the duration between the completion of the primary immunisation schedule and the planned booster dose. So, by that standard, if you look at the Indian example, of course health workers and front-line workers who received the vaccine long before anyone else might come in the category of people who should receive a booster dose before other groups. Also, the elderly. But the elderly may require far more boosting.

I also want to bring the final and slightly related point which is relevant. There is an ongoing discussion and broader consensus that while booster doses require more thinking, an additional dose or third dose as part of the extended primary immunisation schedule for those adults of any age group who are immunocompromised or who could not develop the immune sufficient antibody after two shots of primary schedule should be considered.

Should the focus not be on primary vaccination of the global community, especially in Africa where only a very small percentage of people have been vaccinated? Should India not be focused on distributing vaccines globally than on administering booster doses especially when there is no evidence of benefit?

Satyajit Rath: Well, my short answer to that is, as I said in the beginning of this conversation, the focus needs to be on global inclusive primary COVID-19 vaccination campaigns. And that conversations about boosters remain both unconnected to that primary purpose for reducing hospitalisations and deaths, as Dr. Lahariya pointed out, to a significant extent thin on evidence. Therefore, I don’t see those as in any way ambiguous. Of course, the focus needs to be on primary vaccination campaigns.  

Chandrakant Lahariya: There is enough evidence to say that primary immunisation prevents severe disease, hospitalisation and death. That should be the core focus no matter which part of the world people are living in. Ensuring vaccine availability in different parts of the world should be the priority of all countries. Of course, during a pandemic, countries would want to prioritise their own population first and then share vaccines. I believe that now India can assure primary immunisation for the adult population and it has more vaccines. So, India’s priority should be to revive the Vaccine Maitri initiative in an accelerated and sustained manner. This becomes especially important as new variants are emerging most likely from settings where there is low vaccination coverage.

Even if new variants are not emerging from such settings, their impact would be far worse in those settings. So, if the world wants to halt the pandemic, countries need to vaccinate their own populations but also share vaccines with the rest of the world before considering booster doses. And even when evidence on boosters emerges, there is far greater evidence on the benefit of primary immunisation and that points to the importance of sharing vaccines. India should definitely share its vaccines and now is the time.

Published in The Hindu on December 10, 2021

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