Benaulim and Jaipur: Several countries have reduced the gap between doses of the Oxford/AstraZeneca vaccine (branded Covishield in India) to eight weeks in response to the emergence of the more transmissible Delta variant of SARS-CoV-2, the virus which causes Covid-19. Recent studies both in India and internationally have also shown greater effectiveness of two doses of the Oxford/AstraZeneca vaccine compared to a single dose, especially against the Delta variant. India, however, has not reduced the existing 12- to 16-week dosage interval for Covishield.
This is because India is in a different stage of the pandemic compared to the other countries using the same vaccine, experts have told IndiaSpend. The difference between the effectiveness of a single dose versus two doses is not that large for protection from hospitalisation and severe disease, and India has still not given even a single dose to half the population.
"When vaccine supply is limited, it is more important to cover as many people with one dose as possible. I believe that from a public health perspective, it is the right strategy," said Shahid Jameel, a virologist and visiting professor at Sonepat-based Ashoka University.
We examine the rationale behind India's comparatively longer interval between two doses of Covishield.
What other countries using the Oxford/AstraZeneca vaccine are doing
In India, Covishield is manufactured by the Serum Institute of India on behalf of British-Swedish multinational pharmaceutical and biotechnology company AstraZeneca, and is a version of the Covid-19 vaccine developed by the University of Oxford. Several countries use the same vaccine, manufactured under different names, one of which is Vaxzevria, used in the United Kingdom and in the European Union.
On December 31, 2020, the UK's Joint Committee on Vaccination and Immunisation (JCVI) had said that a longer interval between the first and second doses of the Oxford/AstraZeneca vaccine promoted a stronger immune response. They recommended a 12-week gap between the two doses.
Two weeks later, on January 16, 2021, when India's vaccination programme was rolled out, the two-dose Covishield vaccine was to be administered with a gap of four-six weeks between doses. On March 22, this was increased to six-eight weeks, citing scientific evidence that the increased interval provided enhanced protection. On May 13, during the peak of the second Covid-19 wave, the Covid-19 Working Group's National Technical Advisory Group on Immunisation (NTAGI) recommended the dosage interval for Covishield be extended further to 12-16 weeks.
But the next day, on May 14, the JCVI of the UK advised that the administering of the second vaccine dose in the UK be brought forward from 12 to eight weeks, particularly in areas where the Delta variant was a major threat. The Delta variant is more transmissible than any other variant yet of the Covid-19 virus, and was one of the causes of India's second Covid-19 wave, per a study led by the National Centre for Disease Control in Delhi published in June 2021.
On June 10, Northern Ireland mandated that the interval between first and second doses for the Oxford/AstraZeneca vaccine be a maximum of eight weeks; on June 13, Scotland asked all those over 40 years with second dose appointments scheduled more than eight weeks after the first dose, to seek earlier appointments; and on July 6, England's National Health Service advised acceleration of second doses for all eligible groups "to ensure everyone has the strongest possible protection from the Delta variant of the virus at the earliest opportunity possible".
Some recent studies in India, including at Max hospitals in the National Capital Region (NCR) and at Sir Ganga Ram Hospital in New Delhi, found more breakthrough infections in healthcare workers who had had only one dose of the Covishield vaccine versus two doses.
Nearly half (48.4%) of 597 healthcare workers at four Max hospitals in the NCR who had taken a single dose of the Covishield vaccine, and 25.3% of those fully vaccinated, had breakthrough infections during the Delta variant surge in the capital, the pre-print from August 2021 says. One dose of the vaccine should not be expected to offer much protection against the Delta variant, but "there were no severe infections leading to hospitalisations," the study found. The Max study recommended the dosage interval for Covishield be reduced to six weeks.
In the study at Sir Ganga Ram Hospital, a pre-print published in the European Journal of Internal Medicine in August, a single dose of Covishield offered little protection (18%) against symptomatic infections with the Delta variant, which is lower than that shown by other studies, including those done at the Christian Medical College (CMC), Vellore, in June (61%) and by Public Health England (30%).
Against moderate to severe disease, full immunisation with Covishield afforded 67% protection, but those with one dose had only 37% protection. Full immunisation provided 76% protection against the need for oxygen therapy, but a single dose only 53%. The fully immunised had 97% protection against death and the partly vaccinated, 69%, the study at Sir Ganga Ram Hospital found.
"Two doses are definitely better than one," said Jameel.
Why a longer gap is suitable for India
The rationale of a longer gap between doses is based on the scientific fact that "to maximise the immune response of a vaccine, you should have as long a gap as possible", Gagandeep Kang, a virologist and professor at CMC, Vellore, told IndiaSpend.
When the gap between doses was longer, the efficacy of the vaccine was about 90%, while in trials with a shorter gap, the efficacy was about 60%, said Jameel. "Several studies show that even one dose of the vaccines afford decent protection from severe disease and mortality," he added.
For instance, the study by CMC Vellore showed 70% protection from hospitalisation with a single dose of a Covid-19 vaccine, going up to 77% with two doses. "This study would have been critical in driving India's policy of maximising one-dose coverage," said Jameel. The study of 8,991 staff, vaccinated between January 21 and April 30, 2021, and published in June 2021, did not look at variants responsible for the second wave or distinguish between Covishield and Covaxin; however, 93.4% (8,394) of the staff received Covishield. The Delta variant was found in 96% of samples sequenced from Tamil Nadu in May, per data from the Indian SARS-CoV-2 Genomics Consortium.
It is important to also understand the context of the change in the dosage interval in other countries, said Kang.
When the UK announced the reduction to eight weeks from 12, they said that this advice was "specific to circumstances in the UK at this time", and was "only possible because everyone in the Phase 1 priority groups [including the elderly and those with comorbidities] has already been offered a first dose". The elderly and those with pre-existing conditions, such as diabetes, are more prone to serious Covid-19 and are at higher risk of death.
Similarly, when Scotland reduced the gap in doses to eight weeks, they had vaccinated over three quarters of the adult population with a single dose and over half of the population was fully vaccinated. "We remain on track to offer the vaccine to all adults by the end of July," the Scottish government had said on June 13.
In contrast, 22% of India's eligible adult population and 15% of the entire population were fully vaccinated and another 43% adults had received one dose by September 20. "In India, we are still in a stage where about 65% of over 60s have received only one dose of immunisation. That is not good enough," Kang said.
Require better quality data from India
The Indian studies referenced above were in healthcare settings, and thus include a much lower proportion of the population than countries that have good quality data for larger populations. For instance, the study in Max hospitals included 597 people, while the Public Health England study, published in August 2021, included 19,000 people. "The smaller the study sample, the larger the variation in the findings," said Kang.
"Ultimately, what we should have is data on people in our country--we have given more doses of the AstraZeneca vaccine or Covaxin than anybody else in the world and yet we are generating data from hospitals because healthcare workers are a captive population," Kang added, emphasising the need for better quality data from India.
A single dose of a Covid-19 vaccine in India was 96.6% effective in preventing mortality, and two doses were 97.5% effective, Balram Bhargava, the director-general of the Indian Council of Medical Research (ICMR), India's apex science body, said at a press conference on September 9. This claim was based on the data from ICMR on Covid-19 cases from April 18 to August 15, but no further details or data were provided, including on numbers of breakthrough infections, or which vaccine the data are related to.
Reducing the gap for certain vulnerable populations
India had reduced the Covishield dosage interval to as little as four weeks for persons needing to travel internationally, including students and athletes participating in the Olympic Games.
If India was thinking of reducing the dosage interval for Covishield, they should first do so for the population that is more prone to severe disease or death from Covid-19 or locations where there are currently more cases of Covid-19, experts said.
"If you were to think of a short gap, I am not particularly fussed about an 18-year-old who wants to travel overseas. I am worried about the 70-year-old who has gotten one dose and is having trouble getting the next one," said Kang. For reducing the interval, "I would start with people most vulnerable to serious illness. That would be those 60 years and above and those with existing comorbidities, Jameel agreed.
Further, "with better supplies and reduced daily infections, this would be the right time to evaluate the evidence and possibly bring down the gap to 8-12 weeks", said Jameel. India has administered about 9.2 million doses per day over the week to September 20, compared to 8 million the previous week. It must ramp this up to 10.5 million doses a day to meet its goal of vaccinating all adult Indians by the end of this year, our calculations show.
"The decision would be based on a risk and benefit analysis of how much disease would you alleviate, for which age-group and in which location," as there is a trade-off between two doses for some people compared to single doses for more people, said Kang.
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