Covishield Dosage Gap: Backed By Science or Need for Greater Good?

"The decision is clearly supply driven. That being said, it's the right decision," says Dr Swapneil Parikh.

Covishield Dosage Gap: Backed By Science or Need for Greater Good?

Covishield, India's go-to vaccine against the novel coronavirus, was initially approved under emergency use in January, 2021 with a dosage gap of 28 days. At the time, the UK, first country to approve the Oxford AstraZeneca vaccine, had already recommended the gap of 4-12 weeks.

On 22 March, the government changed the advisory again to say the dosage gap should be extended to 6-8 weeks. At the time, several studies including this one in The Lancet, had established that a 12-week gap produced better efficacy.

On May 13, the Health Ministry accepted the recommendation of the National Expert Group on Vaccine Administration for COVID-19 (NEGVAC), headed by Dr V K Paul, to extend the gap to 12-16 weeks based on 'real world evidence from the UK' of vaccine efficacy.

The shifting of goalpost by India when it comes to dosage gap for Covishield raises an important question - is the decision driven by science, or has the lack of supplies forced the government to adopt the 'greater good' public health measure.

"The decision is clearly supply driven. That being said, it's the right decision," says Dr Swapneil Parikh, an internal medicine doctor and scientist.


What Does the Science Say?

The recommendation was made by the COVID Working Group headed by Dr NK Vohra. The other members include Dr Gagandeep Kang, Dr J P Mulliyal and Dr V G Somani, Drugs Controller General of India (DCGI), among others.

12-Week Gap

In February, 2021, The Lancet, published a study based on data from four different trials and found that Covishield’s efficacy was closer to 55.1% when the dosage gap was less that six weeks. The efficacy increased to 81.3% when administered 12 weeks apart.

Also in February, this article in the British Medical Journal (BMJ), said that a single standard dose of vaccine provided 76% protection overall against symptomatic covid-19 in the first 90 days after vaccination with protection not falling in this time frame.

The UK regulators and European Medicines Agency (EMA) recommend a 12-week gap for AstraZeneca's vaccine. The World Health Organisation (WHO) recommends an 8-12 week gap between doses.

The 16-Week Gap

Some countries like Spain and Canada have extended the gap upto 16 weeks for certain age groups.

But there are no trials that have been conducted to support the 16-week gap.

Spain's decision was driven by the need to evaluate the results of trials on mixing different vaccines before deciding whether those age-groups groups will receive a second AstraZeneca shot or another drug, reports Reuters. This followed the blood-clotting issues reported with AstraZeneca vaccine in parts of Europe.

'In the longer run, 3-month gap will be better than a 1-month gap,' Dr Gangandeep Kang

In an earlier interview with FIT, Dr Gangandeep Kang, microbiologist with CMC Vellore, came out in support of the 12-week gap. Dr Kang is part of the group on whose recommendation the government has decided to extend the gap for Covishield.

Dr Kang said that this will not only help deal with vaccine shortage but also provide better efficacy in the longer run.

“The UK decided early on that for both Pfizer and Covishield vaccines, they will delay the second dose by three months. Now we have real-world-use data of what single dose of AstraZeneca vaccine can achieve. The single dose provides very good protection against hospitalisation and death. So, it can offer protection for at least three months. If there is an issue with the supply, the AstraZeneca vaccine, you can safely delay up to three months.”

“In the longer run too, we might find that the three-month gap is better than the one-month gap. Immunologically, in the long run, extending the gap between two doses will give you longer protection and we don’t want to be running around to get booster dose,” she added.

Speaking with FIT, Dr Swapneil Parikh said,

"It should never have come to this, we should have had better planning in place, but if it didn't happen, we have to work with what we have. In the crisis situation we are in right now, this seems to be the least terrible option. It's about saving more lives."

What About Covaxin? Can We Delay the Second Dose?

For now, the panel has not recommended any change to the 28-day dosing schedule for Covaxin. Full Phase 3 data for Covaxin is still not released by Bharat Biotech, the makers of the vaccine. Neither is there publicly- available data on the efficacy of a single dose Covaxin, or for that matter any real-world data that has examined it.

But Dr Parikh points out to an interesting model that assesses public health impact of delaying second doses.

Published in The BMJ, the model looked at Pfizer's mRNA vaccine and ran a simulation of standard vaccination schedule versus delayed second dose vaccination prioritizing the first dose.

The result indicated a delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.

While this simulation looks at Pfizer's vaccine, Dr Parikh says, "If the efficacy of single-dose of Covaxin is above 70 percent, we could consider a strategy for Covaxin where we ensure those above the age of 65 continue to get their second dose as per the 28-day schedule. And we could delay the second dose for those 45-65 year olds upto 90 days."

Six Month Wait After Infection for the Jab

A second recommendation by the National Immunization Technical Advisory Group, yet to be adopted, is on waiting for six months after COVID infection to take the vaccine.

On May 1, the Health Ministry had come out with guidelines on when you can take your second dose after infection. The recommendation was 2-8 weeks after symptoms have subsided.

So what should really be the gap?

The WHO doesn't specify a gap.

The US CDC doesn't specify a gap if you recovered naturally, however it recommends that if you were treated for COVID-19 with monoclonal antibodies or convalescent plasma, you should wait 90 days before getting a COVID-19 vaccine.

There isn't enough data to say how long natural immunity from an infection will last, but there is data to suggest that even if antibodies were to disappear, you will be protected by T Cell immunity.

"We know that even if you were to get reinfected, it's unlikely to be severe," Dr Parikh says, "Right now we are not thinking about what's best for an individual, but about what's best for a collective."

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