Should India reduce the gap between Covishield doses based on UK data?

On May 13, when the Indian government increased the duration between two doses of the Covishield vaccine to 12 weeks-16 weeks from eight weeks-six weeks, it cited “real life evidences, particularly from UK”.

The decision, according to members of India’s Covid Working Group that recommended it, was driven by studies that suggested that the first dose of the vaccine, developed by Oxford University and the British-Swedish company AstraZeneca, provided substantial protection.

Now new “real life” data released by Public Health England on Saturday indicates that the protection offered by one dose of the vaccine could be considerably lower than previously thought, particularly against the B.1.617 variant. Genome sequencing data shows that the variant, first found in India, was found in 65% of samples sequenced.

However, members of India’s Working Group say it is too early to change track once again. “We don’t intend to blindly follow the UK,” said NK Arora, the scientist who chairs the group. “Our peak of this epidemic is already over. We have already faced the music of B.1.617 variant.”

New data, new revelations

Arora said the decision to increase the duration between the two doses of Covishield, known as the Oxford-AstraZeneca vaccine in the UK, was “based on PHE (Public Health England) data that was showing that effectiveness after one dose is around 65% and 88%”.

A study published in the British Medical Journal on May 13 had pegged the efficacy of one dose of Oxford-AstraZeneca vaccine in protecting symptomatic infection as high as 70%. It was based on Public Health England’s data.

Similarly, another study from Scotland published in The Lancet in April comprising “almost the entire Scottish population” found that one dose of the vaccine provided protection against hospitalisations due to Covid-19 by upto 88%.

But these studies did not take into account the B.1.617 variant that was first detected in India in October, and has since been found in 44 countries.

In fact, the data released by Public Health England last Saturday is the first of its kind which has real life insights on the effectiveness of vaccines against the B.1.617 variant. Unfortunately, it is not particularly encouraging.

It states that one dose of the Oxford-AstraZeneca vaccine is only 33% effective against symptomatic infection caused by the B.1.617 variant. With two doses, the efficacy goes up to 60%. The corresponding numbers for the Oxford-AstraZeneca vaccine vis-a-vis the B.1.1.7 variant, first reported in the United Kingdom, is 50% and 66%.

Even before data was available on vaccine efficacy against B.1.617, the United Kingdom, taking into account the greater infectiousness of the variant, reduced the interval between the two doses from 12-weeks to eight weeks on May 15.

But neither the infectiousness of the B.1.617 variant, nor the seemingly low protection afforded by one dose of the Oxford-AstraZeneca vaccine against it, was reason enough to reduce the gap between the two doses, insist members of India’s Working Group.

Not a game-changer (yet)

Director of the Jawaharlal Institute of Postgraduate Medical Education and Research in Puducherry, Rakesh Agarwal, one of the seven members of the Working Group, said “one study does not change everything”. “You can’t go by each individual study,” he said. “It has to be an overall assessment.”

Epidemiologist Jayaprakash Muliyil, also part of the Working Group, said “symptomatic infection” – the yardstick taken into account in Public Health England’s latest analysis – was not a very useful metric. “It is a very, very loose definition,” said Muliyil. “Remember AstraZeneca is meant to protect from severe disease.”

Public Health England’s study has no data on the vaccine’s efficacy against hospitalisation and mortality owing to “insufficient” number of cases and follow-up periods.

Therefore, the findings ought to be looked at in that context, said Muliyil. “I wish it had shown higher protection,” he said. “But I can understand why it did not show higher protection – because it was based on self-reported symptoms.”

Muliyil was referring to the fact that all breakthrough infections with any symptom – however mild – were counted as a symptomatic case in the study on the basis of self-reporting, possibly making the numbers worse than they really were.

“As a country, we want the vaccine to prevent serious disease, not mild symptoms,” he said, adding that evidence from clinical trials around the world suggested that the vaccine was successful in doing that.

More data required

Muliyil’s colleague on the Working Group, virologist Gagandeep Kang pointed out to NDTV that there was no real-world data to establish that the second dose of the vaccine given at eight weeks gave greater protection than at 12 weeks.

But the new revelations definitely merited a deeper engagement, Kang told NDTV. “Before we went to the second wave, we already had 80% exposure in some urban areas and in rural areas 20-odd percent based on the ICMR sero-surveys,” she said, referring to the Indian Council of Medical Research’s efforts to map infections through antibody tests. “It means two exposures – one being natural infection and other through the vaccine. Will it behave like two doses of the vaccine? It is really urgent that we try to get this information.”

Not just a matter of science

Some critics share a bleaker view of the situation. The extension of the duration in the first place, they believe, was not so much based on science as simple demand-supply issues – despite the government’s repeated insistence to the contrary.

To expect a change in policy in the face of new evidence is only wishful thinking, critics say. T Jacob John, one of India’s most well-known virologists, said it was clear from the latest data that “recipients of one dose are at risk”. “If you change policy now, can you manufacture vaccines?” he asked. “Bad early planning has led us here.”

Muliyil, for all practical purposes, agreed. “We are not saying do not give two doses, but given the very limited number of vaccines available, it (the decision to increase the duration) is a strategic move to make sure as many people as possible, at least in the vulnerable age groups, get at least one dose,” he said. “What is the point of giving them after six months?”

But Anurag Agarwal, director of the Council of Scientific and Industrial Research - Institute of Genomics and Integrative Biology told The Hindu that while it was important to cover as many people as possible with one dose, it would also be prudent to double vaccinate at least the country’s vulnerable population at the soonest.