Sunday, April 11, 2021

How Did the Astra Zeneca-Oxford Covid - 19 vaccine go from 'game changer' to 'under review' (SCMP)

 

Health & Environment (South  China  Morning Post)

How did the AstraZeneca-Oxford Covid-19 vaccine go from ‘game changer’ to ‘under review’?

·        Safety concerns about rare blood clots and controversy over slow deliveries threaten to derail the roll-out of the vaccine in many countries

·        Medical experts say it is important that all potential risks are reported, but they worry that the negative attention could shatter public confidence in Covid-19 inoculations

John Power

John Power

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Published: 12:30pm, 10 Apr, 2021

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Countries around the world have moved to address safety concerns around the AstraZeneca-Oxford coronavirus vaccine. Photo: TNS

Cheap, highly effective and easier to distribute than rival jabs, the AstraZeneca-Oxford vaccine was hailed as a game-changer in the global fight against 

Covid-19

.

Months after it was first approved for use in Britain in December, a public relations crisis over extremely rare side effects threatens to derail vaccination efforts in numerous Asia-Pacific and lower-income countries. Countries across the European Union and Britain have already imposed age restrictions on the use of the shot, including offering alternatives to those under 30.

But with the vaccine already used in more than 100 countries – and accounting for almost a quarter of supply deals this year, according to London-based research firm Airfinity Limited – authorities from Sydney to Manila to Seoul are scrambling to review their roll-out of the jab.

The European Medicines Agency on Wednesday said there was a probable link between the vaccine and a tiny number of unusual blood clots. The EMA’s analysis was based on a review of 86 instances, including 18 fatalities, reported as of March 22 among some 25 million people who received the AstraZeneca shot in Britain and Europe. On April 4, there had been 222 reported instances of that type of clotting out of about 34 million people.

The EMA said it had not identified specific risk factors and the overall benefits outweighed the risk of side effects from the vaccine, which is 76 per cent effective at preventing infection based on Phase 3 trials in the US.

It was the latest in a string of publicity headaches for AstraZeneca, which teamed up with an Oxford University team led by vaccinologist Sarah Gilbert to produce the viral vector vaccine, which was developed using a harmless chimpanzee virus as a Trojan Horse to trick the immune system into action.

The Anglo-Swedish company has consistently struggled to meet its supply commitments, sparking backlashes from European and Asia-Pacific governments, and last month slashed by two-thirds its target of delivering 90 million jabs to the European Union within the first quarter.

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In late March, the US National Institute of Allergy and Infectious Diseases raised concerns the company had provided “outdated information” about its latest clinical trials, a snafu that ultimately had no bearing on the vaccine’s safety and only a marginal impact on its demonstrated efficacy.

Jerome Kim, director general of the International Vaccine Institute (IVI) in Seoul, South Korea, said the latest safety concerns created “confusion, worry, and some reactions that are probably unjustified”.

“It may cause countries to default to vaccines that are available but are not yet through WHO approval,” Kim said.

“There will be other vaccines but getting them approved, made and distributed will result in further delays, further infection and further possibility of mutant virus generation.”

The Covax Facility, a World Health Organization-backed initiative to ensure equitable global vaccine access, is highly reliant on the AstraZeneca shot, which is easier to distribute and four to five times cheaper than rivals from Pfizer/BioNTech and Moderna. The Pfizer shot also requires ultra-cold storage. 

Vials of the AstraZeneca Covid-19 vaccine sit in a fridge at a vaccination centre in Germany. Regulators expressed concerns about potential side effects from the vaccine. Photo: AP

RISKS

By all accounts, the potential risks of the AstraZeneca vaccine are statistically minuscule.

The European regulator estimated blood clots affected about one in 100,000 people who were given the vaccine; Britain’s Medicines and Healthcare products Regulatory Agency put the risk even lower, at one in 250,000 vaccinations, based on a review of 79 cases, 19 of which were fatal. 

Based on the British figures collected after more than 20 million vaccinations, the likelihood of dying from the jab stands at around one in 1,000,000. By comparison, there is an approximately one in 500,000 chance of being hit by lightning in a given year, according to the US Centers for Disease Control and Prevention.

The risk of dying of Covid-19 ranges from higher than one in 10 for people in their mid-seventies or older, to practically zero for those below 50.

Hsu Li Yang, an infectious diseases expert at the National University of Singapore’s Saw Swee Hock School of Public Health, said it was difficult to apportion blame over the controversy given the tiny risks involved and the adherence of standard safety protocols.

“I do not think there is any real blame here,” Hsu said. “The adverse effect in question is very rare – perhaps 4 per million vaccinated would develop this condition, which is why it was not picked up in the licensing clinical trials involving tens of thousands of subjects. It is testimony to the close monitoring of adverse effects post-Covid vaccination in the UK and EU countries that allowed such a rare side effect to be picked up so quickly.”

AstraZeneca has said it is studying the individual cases to understand the “epidemiology and possible mechanisms that could explain these extremely rare events”. It is also working with regulators on their request for new labels on its shots.

SCMP Explains: What’s in a Covid-19 vaccine?

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GLOBAL FALLOUT

Nonetheless, authorities have moved swiftly to address safety concerns about the vaccine.

In Hong Kong, Secretary for Food and Health Sophia Chan Siu-chee on Friday announced the government had requested AstraZeneca to postpone the delivery of 7.5 million doses to the city.

“The main reason is because we already have enough supplies,” Chan said, adding that she was also concerned about reports of side effects. “We have also begun looking at next-generation vaccines that can offer better protection against new virus variants.”

The move came after several experts, including government adviser David Hui Shu-cheong, called on Hong Kong to replace its AstraZeneca order – which was due to arrive midyear – with the Johnson & Johnson vaccine, citing the risk of adverse reactions and reduced efficacy on coronavirus variants. The city’s vaccination drive, which has been mired by sluggish uptake, has so far relied on the Sinovac and Pfizer vaccines. 

On Friday, Australia said it had doubled its order of the Pfizer vaccine as authorities raced to overhaul their inoculation plan originally based on the AstraZeneca shot, which called for 50 million doses – enough for the required two shots for its entire 25 million population – to be made domestically by biotechnology company CSL Ltd. The Australian manufacturer said it remained committed to fulfilling its order after producing about 1.3 million doses since March, with plans to ramp up production to 1 million doses a week. 

Canberra has fallen far short of its goal to administer at least one dose to 4 million people by the end of March, blaming the delayed delivery of 3.1 million AstraZeneca doses from Europe, and is now widely expected to miss its October target of administering at least one dose to the entire population. 

New Zealand Prime Minister Jacinda Ardern said the AstraZeneca vaccine was still going through the approval process in the country and only the Pfizer vaccine was currently being administered.

South Korea, which has secured AstraZeneca doses for about 10 million people, on Thursday lifted restrictions on administering the vaccine after briefly suspending inoculations for people under 60. Medical authorities stressed the importance of keeping up the vaccination drive, which saw President Moon Jae-in last month receiving his first AstraZeneca shot.

Health authorities, which have also approved the Johnson & Johnson and Pfizer vaccines and hope to reach herd immunity by November, plan to make an official decision on the roll-out of the AstraZeneca vaccine on Sunday. 

 

A nurse inoculates a woman with a dose of the Covishield/AstraZeneca-Oxford Covid-19 vaccine in Mumbai, India. Photo: AFP

India, which is producing the AstraZeneca-Oxford vaccine locally under the name Covishield, said it was re-examining data on adverse reactions, with a report from the health ministry expected within days.

New Delhi, which aims to vaccinate 250 million people by the end of July, is considered unlikely to restrict the roll-out of Covishield, which has accounted for about 90 per cent of the over 90 million vaccine doses administered in the country. The Serum Institute of India is currently producing about 60 million Covishield doses each month, compared with about 4 million doses of the locally developed Covaxin, India’s only other approved vaccine, which Prime Minister Narendra Modi received his second shot of this week.

“It is a non-issue for India given the size of our population and the fact that Covishield is the mainstay of our campaign,” said Dr Arun Shah, a paediatrician in New Delhi.

Thailand, which briefly suspended the roll-out of the AstraZeneca jab last month due to safety concerns, has so far given no indication of any changes to its vaccine drive, under which Siam Bioscience, a firm owned by King Maha Vajiralongkorn, plans to produce 61 million doses of the British-Swedish vaccine. 

The Philippines on Thursday suspended AstraZeneca shots for people below 60, while Indonesia, which has a warning against using it in people with a low blood platelet count, said it had reached out to China for more vaccine supplies after delays in AstraZeneca deliveries.

In the rest of the world, more than a dozen countries have at one time suspended use of the AstraZeneca vaccine, but most have resumed, with some, including France, the Netherlands and Germany, recommending a minimum age. Bloomberg reported that the US stockpile of the jab had grown to more than 20 million doses, even as the shot looks increasingly unlikely to factor in President 

Joe Biden

’s domestic vaccination campaign.

FUELLING HESITANCY

Experts are worried that scepticism about the AstraZeneca vaccine, already running high in some EU and Asia-Pacific countries, will spread given the controversy. 

In Thailand, the death of a 71-year-old deputy abbot at a Buddhist temple in Bangkok soon after receiving the AstraZeneca jab has stoked safety concerns. Authorities said the monk suffered from obesity and high blood pressure, although his autopsy results are yet to be released.

Phra Jirakit, who shared the Samphanthawong temple with the deceased monk, said many of his fellow monks were now reluctant to take the shot.

“I might wait if other vaccines are available in Thailand before I can decide to get the second AstraZeneca dose,” he said. “If the deputy abbot’s death can help benefit science then we don’t want to blame anyone. I want to wait for a firm study to come out first.”

The rare and as yet ‘unexplained’ blood clots were caught by a safety system that is in place to detect these eventsJerome Kim, International Vaccine Institute

Parminder Verma, a 62-year-old maths tutor in New Delhi, said she was concerned about her 26-year-old son receiving the vaccine as he suffers from the rare blood disorder eosinophilia, which can cause blood clots. 

“We don’t even know if the blood clot happens after the first dose or the second dose,” said Verma, who has received her first dose of Covishield along with her husband and had until recently been anxious to ensure her son is also vaccinated. “We know nothing about the age, sex or health conditions of those affected.” 

Sanghamitra Acharya, professor at the Centre of Social Medicine and Community Health at Jawaharlal Nehru University in New Delhi, said it would be crucial for authorities to dispel the “mystery of the vaccine”.

“In simple language, it needs to be explained to the people what the vaccine is and how it will protect from infection of Covid-19,” Acharya said. “Clear message and assurance is the key.”

Syringes are prepared to administer the AstraZeneca Covid-19 shot at a mass vaccination centre in Madrid. Photo: Reuters

One prominent vaccine expert in Australia, who wished to remain anonymous due to the sensitivity of the situation, said he was deeply concerned about the impact the negative attention could have on the global vaccine roll-out, suggesting Australia’s advisory was an example of messaging that would likely shatter public confidence in the jab.

“Like the curate’s egg, the AstraZeneca vaccine will now be seen to be good in parts,” he said, adding that while authorities could not deny there was any issue, it was important not “make more of it than it is”.

Dale Fisher, a professor at the Yong Loo Lin School of Medicine at the University of Singapore, said while the adverse reactions were “inconvenient” to the roll-out, authorities had to be honest with the public about the risks. 

“A very, very, rare event in thrombotic thrombocytopenic purpura is more common after the vaccine but still very rare,” Fisher said. 

“Probably it is less likely than having a serious car accident on the way to the vaccination centre. People are aware that serious car accidents occur and take the risk as it’s a way of life. This small risk of this vaccine in the order of 1 in 250,000 is to restore our way of life and indeed save lives.”

But Fisher admitted communicating the necessity of vaccinations despite the minuscule risk would be difficult as people tended to be “much more prepared to take risk for a treatment, such as surgery, than they are for prevention”.

Kim of the IVI said it would be up to authorities in different countries to weigh the costs and benefits of the AstraZeneca-Oxford shot based on factors such as local demographics and the prevalence of the virus among the population.

But he expressed hope the jab would continue to see widespread use, alongside existing rivals and other vaccines that are yet to come online.

“The rare and as yet ‘unexplained’ blood clots were caught by a safety system that is in place to detect these events,” Kim said.

“The development of policy statements by EMA and many governments have been based on evolving data, and you want that. I hope that we will be able to find a way to use this vaccine safely, that other existing approved vaccines continue to full rate production, and that the as-yet-unapproved vaccines are brought forward, reviewed and approved as appropriate.”

Additional reporting by Bloomberg and Agence France-Presse

 

 

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