Outlining the very legitimate concerns with Serum Institute of India’s Covishield vaccine, which makes up almost 90% of all COVID vaccines administered in India, PREM ANAND MURUGAN explains why several countries across the globe have discontinued or limited the use of the AstraZeneca-Oxford COVID vaccine, and recommends that Indian State authorities inform the public about these concerns as well as arrange for alternative vaccines to reduce our dependence on Covishield for vaccinating the majority of our population.
AS of May 28, 2021, India has administered a total of 205 million doses of COVID vaccines in total to its citizens. Of those, 89.8% doses are of Covishield from the Serum Institute of India (SII) (Covishield) and 10.2% are of Covaxin from Bharat Biotech.
The Union Health and Family Welfare Minister has promised that all adults will be vaccinated by the end of 2021, as the union government has planned to procure 267 crore vaccines. Assuming that this happens on schedule, most of the vaccinations are going to be done via the Covishield vaccine. Covishield is the AstraZeneca-Oxford vaccine ChAdOx1.
Approval story of Covishield by Indian regulators
Covishield was approved in India for emergency use by the Drug Controller General of India (DGCI) on recommendation of the Subject Expert Committee (SEC) meeting held on January 1, 2021. The approval was given based on the data shown by SII. As per the published details of the SEC meeting on December 30, 2020, this data consisted of the results of the AstraZeneca vaccine Vaxzevria’s (the United Kingdom version of Covishield) clinical trials carried out in the UK, Brazil and South Africa, which had been earlier that month published in the medical journal The Lancet.
According to a press release by SII on November 11, 2020, “[Covishield] is by far the most advanced vaccine in human testing in India. Based on the Phase 2/3 trial results, SII, with the help of ICMR [Indian Council of Medical Research], will pursue the early availability of this product for India.”
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However, by this time, the clinical trials of Phase II/III had not begun. In fact, data for Phase II/III clinical trials of 1,600 participants in India was shared by SII only on January 28, 2021. The duration of the experiment was stated as seven months in the Clinical Trial Registry of India.
According to the news service Clinical Trials Arena, on April 27, 2021, an SII spokesperson had admitted that he did not know when the three-month data of Covishield clinical trials was submitted or when they expect to hear back from Central Drug Standard Control Organization (CDSCO).
To summarize, the emergency approval of Covishield in India was based on Vaxzevria data that was obtained from overseas, and not from India clinical trials of Covishield vaccine. This, even when the Pfizer COVID vaccine was not accepted for emergency use on the grounds that safety and immunogenicity data in Indian population for the same was not available at the SEC meeting on February 3, 2021.
Also read: Pfizer Withdraws Emergency Use Request For COVID-19 Vaccine In India
India’s emergency approval of AstraZeneca’s COVID vaccine needs to be contrasted with the vaccine’s fate in the United States, where it has not yet been authorized for use, even though the US has a stockpile of the vaccine available with it. The reason for denial given was the insufficiency of data submitted to the US federal agency Food and Drug Administration by AstraZeneca. It is noteworthy to mention that the US had given AstraZeneca more than $1 billion to develop and study its COVID-19 vaccine.
What are the concerns with Covishield?
Earlier this month, a report about Adverse Event Following Immunization (AEFI) confirmed that upon the administration of Covishield, there were 23,000 adverse events reported through the CO-WIN platform as of April 23, 2021. Only 700 of those were considered severe by the National AEFI Committee. Among those, 26 cases were reportedly due to thromboembolic events (0.61/million cases). Thromboembolic events refer to the formation of a clot in a blood vessel that might also break loose and get carried by the bloodstream to plug another vessel.
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The committee stated that this was much less than the number of thromboembolic events reported by the UK’s Medical and Health Regulatory Authority (MHRA) and by Germany. In the UK, about four in a million vaccinated persons, and in the European Union, about ten in a million vaccinated persons, on average, reported thromboembolic events.
Comparing these numbers might indicate the risk is minuscule for Indians. But before concluding this, there are some things to be taken into consideration. One of them is the age factor: most people vaccinated in India are in the age group of 45 years and above, which might mask the real extent of the number of serious complications.
AstraZeneca vaccine limited, barred from use by several European countries
For example, in the UK, it was observed that the younger the age of the adult, the more the risk of harmful effects from the vaccine. These incidence rates were found through the COVID-19 infection survey systematically conducted by the Office of National statistics. It was also found that people with low exposure risk of COVID-19 and those aged below 40 technically had a higher probability of getting complications from the vaccine rather than from COVID-19 itself. The potential risks outweigh the benefits in those cases. Hence, the UK has offered alternative vaccines to AstraZeneca for people under the age of 40.
France has also limited the use of the AstraZeneca vaccine to people above the age of 55 years. Studies in Norway and Denmark also observed the same level of risk as that observed by the European Medicines Agency. They both dropped the AstraZeneca vaccine from their public vaccination drives in the last two months. Japan recently approved the use of the AstraZeneca vaccine, but is considering age limits for the same, and is delaying the use of the vaccine.
The Global Advisory Committee on Vaccine Safety (GACVS) also recommends constant screening of platelet and radiological studies of people who are at the risk of blood clots due to vaccine. Germany had also stopped the AstraZeneca vaccines by March 2021 for people under the age of 60 years before opening it for all adults earlier this month due to the lack of availability of sufficient alternative vaccines.
The Democratic Republic of Congo last month returned 1.3 million doses of the AstraZeneca vaccine to the COVAX (COVID-19 Vaccines Global Access) Initiative facility due to concerns over blood clots in younger population. Reflecting on this, the Director of the Africa Centres for Disease Control and Prevention, the public health agency of the African Union, stated that poor African nations do not have the luxury of choosing their vaccines.
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Similar voices have been heard in India. Virologist Dr. Gagandeep Kang of the Christian Medical College, Vellore said, “[I]t is affecting vaccine confidence to some extent. But I also don’t think that we really have a choice, because we don’t have the infrastructure to distribute the Pfizer and Moderna vaccines.”
Already several European countries such as Spain and Germany that have used the AstraZeneca vaccine have started trials for the mixing and matching of vaccines (for instance, the Pfizer vaccine after the AstraZeneca one) so that it can avoid the use of AstraZeneca vaccine for second doses due to safety concerns. The study has shown positive results so far.
Need to move away to other COVID vaccines
Sputnik, the other vaccine approved for use in India, is also based on the same type of adenovirus vaccine as the AstraZeneca vaccine; therefore, it might also pose the same risk factors. As Dr. Ashish Jha, Dean at the Brown University School of Public Health has stated, we need a global strategy to move away from the AstraZeneca vaccines towards others.
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Therefore, India would be better served to secure alternative vaccines for vaccinating most of the large demographic of its young population. Even though it is not possible immediately, the Indian government and CDSCO should at least conduct proper monitoring and follow-up of the population vaccinated with Covishield, as recommended by GACVS. It should also make the public, particularly the younger population, aware of the side effects so that people are prepared to get medical attention in time, if and when required.
Yes, it may affect the confidence of vaccination, but citizens ought to be fully informed of all possible concerns.
(Prem Anand Murugan is a Ph.D. student at the Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur. The views expressed are personal.)