It is well known that two doses of COVID vaccination – whether it is Pfizer, Moderna, AstraZeneca/Covishield or Covaxin – offer excellent protection against moderate and severe COVID (95-97%) but not against mild and asymptomatic disease (28%). Booster doses have been a matter of speculation since the early days of COVID vaccination when it was suggested that annual shots may be needed. The USFDA officially approved the use of 3rd dose of COVID vaccination for immunocompromised patients on 12th August 2021 in the face of criticism even from staunchly pro-vaccination doctors such as Paul Offit. On 18th August 2021, US President Joe Biden stated that his government had been preparing for administration of a third dose of the vaccine since the past few months. Several scientists and mainstream journals have questioned the need for a booster dose of the vaccine. Dr Anthony Fauci stated in the context of Pfizer’s trials of a third dose that a booster would most likely be required some time in the future as the action of COVID vaccines was not likely to be forever. In India, Bharat Biotech has initiated trials for a booster dose of Covaxin. Serum Insitute of India Chairman Cyrus Poonawala also set the cat among the pigeons by claiming that he had taken a third booster dose and also given it to the entire staff of SII, and that all should take it.

But is a third dose needed at all? And if so, who should take it?

The discussion of booster dose revolves around the fact that protection is considered lower for new variants such as delta and delta plus, and waning levels of antibodies have been documented over time. However, the protective effect of vaccination against moderate and severe disease is still excellent for variants as T-cell and B-cell immunity is still maintained. Hence the role of a booster is far from certain. In May 2021, the UK government started a trial for evaluating efficacy of seven different COVID vaccines. This trial is expected to run for upto a year before drawing any conclusions. Moderna has completed a trial of third dose booster and found titers post third dose approaching levels seen after the first vaccine administration. However, it has also observed that protection after two doses continued to be excellent after six months. In the US, admission data reveals that only 8054 fully vaccinated persons needed admission for breakthrough infection from May to August 2021, as against the total weekly admissions of around 11,000. Out of these 8054 hospitalizations, 29% of admissions in fully vaccinated persons were for other illnesses and not COVID and average age of the hospitalized persons was 82. This is a clear indication that the present two doses of mRNA vaccines are indeed continuing to work well despite claims of decreased efficacy due to variants.

The AstraZeneca / Covishield vaccine was initially planned as a single-dose vaccine as it was found to generate a robust immune response in phase 1 trials. It was later modified into two doses. The company has experimented with the interval between two doses. Initially an interval of 4-6 weeks was maintained but later, the company claimed that delayed administration of the second dose at 12 weeks led to better immune response. Yours truly has strongly criticized the Lancet trial which governments across the world relied on while deciding to administer a delayed second dose. But it is less known that a trial from Oxford had claimed that second dose of AstraZeneca vaccine administered ten months after the first dose showed a good immune response. If the efficacy of a single dose lasted for over ten months, it makes very little sense for a third dose to be given a year after initial two-dose vaccination. The official stand of AstraZeneca is that it is unclear whether a third dose is needed.

Israel, despite being one of the most vaccinated countries in the world, is seeing a surge in the number of fresh cases. Due to this Israelis are now being offered a third dose of the vaccine. However, the total number of admissions is only around 600 out of whom half are unvaccinated (as compared to 78% of population over 12 years vaccinated). Israeli doctors say that vaccinated patients tend to have faster recovery and shorter stay compared to unvaccinated ones even without the booster dose. Moreover, doctors have argued that the apparent failure of vaccination may be nothing more than an artefact as data on breakthrough infections does not consider the other parameters of the patients. According to Noa Elilakin-Raz, head of Coronavirus ward at Rabin Medical Centre in Petach Tikva,

“The vaccinated patients are older, unhealthy, often they were bedridden before infection, immobile and already requiring nursing care. In contrast, the unvaccinated COVID patients we see are young, healthy, working people and their condition deteriorates rapidly. Suddenly they’re being put on oxygen or on a respirator.”.

According to preliminary data issued by the Israeli Ministry of Health, a booster dose significantly reduced risk of hospitalization by 50%. But experts have warned against considering the booster a permanent solution, pointing out to poor compliance with masking and distancing in the population.

Certain high-risk groups such as transplant recipients and patients on immunosuppressive treatment are known to have poor immune response to vaccination and hence in these sub-groups, a third dose has always been likely. The unfortunate demise of renowned cardiologist Dr KK Aggarwal, who tested negative for antibodies despite two doses of vaccine due to his ongoing immunosuppressive treatment, is a case in point. A study has formally confirmed this benefit. This small subgroup of people are definite candidates for booster doses and this is not unusual, as this group is usually administered influenza and pneumococcal vaccines annually as well.

It is not clear whether otherwise healthy senior citizens should be administered a third dose of the vaccine. But as far as non-high risk population is concerned, as of now a third dose is not required. It makes little sense to give a third shot of AstraZeneca vaccine to the entire population. Recent statements of Serum Institute of India Chairman Cyrus Poonawala requesting people to take a third dose of the vaccine should be taken with caution as it is not backed by any scientific study as of now, and also not recommended by the Health Ministry of India.

If a booster is needed due to any of the above mentioned reasons, a “mix and match” approach may work better than administration of an additional dose of the same vaccine. A trial conducted on 600 volunteers who received a dose of AstraZeneca followed by Pfizer vaccine showed excellent immune response. An important point to be noted here is that each dose of mRNA vaccine leads to higher response whereas repeated doses of AstraZeneca vaccine lead to relatively dampened immune response. AZ is conducting joint trials with Sputnik V and the results are expected shortly. The company is also testing a modified version of their vaccine that is specific to the beta variant.

In summary, a third dose of COVID vaccine will prove beneficial in high risk population but make no substantial difference for people without existing serious illnesses. Extending it to the entire eligible population is not needed and the benefit would be questionable.