RPT: ANALYSIS - AstraZeneca, J&J COVID-19 Vaccines Face Scrutiny Over Blood Clot Link

MOSCOW (UrduPoint News / Sputnik - 16th April, 2021) Medical regulators across the globe are rushing to study the blood clot disorders that have been reported in a small proportion of people who have received COVID-19 vaccines developed by AstraZeneca and Johnson & Johnson, and experts told Sputnik that more needs to be done to identify if there is a causal link between the adverse clotting events and the two vaccines.

Both the AstraZeneca and Johnson & Johnson vaccines are based on a technology known as a "viral vector." They use an adenovirus, an inactivated form of a virus that can cause the common cold, to transfer information to human cells that leads to the creation of coronavirus proteins that subsequently offer the individual protection against COVID-19.

Viral vector vaccines, including Russia's Sputnik V and the Canadian-Swedish CanSino vaccine, are cheaper to produce and easier to store than vaccines produced by Pfizer and Moderna that operate on mRNA, or messenger RNA, technology, which helps cells assemble proteins without the need for a virus to be injected.

As a result, the AstraZeneca vaccine forms a core part of the Gavi and World Health Organization (WHO)-led COVAX vaccine distribution initiative.

WORLD RUSHES TO ANALYZE BLOOD CLOTTING EVENTS

As mass vaccination programs gained speed following their launch this past winter, several European countries, including Denmark and Norway, temporarily suspended the use of AstraZeneca's COVID-19 vaccine in March following reports that several individuals developed blood clots after they received a shot.

Experts from the European Medicines Agency (EMA) and the WHO launched urgent safety reviews into the blood clot events.

On March 18, EMA Executive Director Emer Cooke told a press briefing that the agency's Pharmacovigilance Risk Assessment Committee had concluded that the vaccine "is not associated with an increase in the overall risk of thromboembolic events or blood clots."

According to EMA data, 169 cases of cerebral venous sinus thrombosis, where blood clots form on the brain, were reported in individuals, mostly women, who received the AstraZeneca vaccine. A further 53 cases of individuals developing blood clots in the abdomen were reported.

The EMA's guidance was subsequently updated on April 7, as experts from the agency issued a recommendation that "unusual blood clots with low blood platelets" should be listed as "very rare side effects" of AstraZeneca's COVID-19 vaccine.

One week later, the Danish health authorities announced that they would pull the AstraZeneca vaccine from the country's mass COVID-19 immunization program entirely.

Johnson & Johnson's single-dose viral vector vaccine has also run into difficulties following its launch in the United States.

Out of the roughly 7 million doses of the vaccine administered in the US, six cases of blood clot events combined with low platelet levels were reported. All six were women aged 18 to 48, and, according to media reports, one individual died and another was hospitalized in critical condition.

On Tuesday, the US Centers for Disease Control and Prevention (CDC) issued a joint statement with the food and Drug Administration (FDA) recommending a pause in the use of the Johnson & Johnson vaccine pending further review. The company said that it would also pause planned deliveries of the vaccine to Europe.

Top US infectious disease expert Anthony Fauci told the NBC broadcaster on Wednesday that there were "rather strong similarities" between the blood clotting events seen in a small number of individuals who received either the Johnson & Johnson or AstraZeneca vaccines; leading to a new round of questions and inquiries into the safety of vaccines that use adenoviral vectors.

NOT ALL ADENOVIRUS VECTOR BASED VACCINES HAVE PROBLEMS

A handful of adenoviral vector vaccines are currently on the market, including an Ebola vaccine produced by Johnson & Johnson, although none are currently being used in immunization initiatives of the scale of the current COVID-19 mass vaccination program.

There are also marked differences in the type of adenovirus used by AstraZeneca and Johnson & Johnson. The former uses a chimpanzee adenovirus vector, the latter - a human adenovirus vector.

Russia's Sputnik V COVID-19 vaccine also uses a human adenovirus as its viral vector, although the vaccine's developer, the Gamaleya National Center of Epidemiology and Microbiology, has urged members of the public not to make direct comparisons between the three viral vector vaccines.

"All vaccines based on adenoviral vector platform are different and not directly comparable," a statement published on Wednesday read.

The Gamaleya Center said that it was not aware of any blood clot events reported in individuals who received the Sputnik V vaccine, and experts at the Russian institute hypothesized that this could be due to the different components of each individual vaccine, or the varied purification methods used by manufacturers.�

"Sputnik V vaccine is produced with the HEK293 cell line, which has long been safely used for the production of biotechnological products," the Gamaleya Center said, noting that the Johnson & Johnson vaccine uses the PER.C6 cell line, which is "not widely represented among other registered products."

George Rutherford, a professor of epidemiology at the University of California, San Francisco, told Sputnik that it could be significant that no adverse blood clotting events have been reported in individuals who have received the Sputnik V vaccine.

"If they've done a similar number of vaccinations worldwide and haven't seen this that means something, potentially. It may mean the vector, which is slightly different, it may mean the cell lines that the adenovirus is raised in, it may mean something else," Rutherford said.

The developer of the CanSino vaccine, CanSino Biologics, has also reported no adverse thromboembolic events in individuals who have received doses of the vaccine, and Rutherford said that more needed to be done to study the differences between the four leading adenovirus vector vaccines currently in use.

"But the fact that there are four, and we've seen these complications with two, and not reported so far with the other two, may mean there's something different between the two that have it and the two that don't," the UCSF academic said.

According to Cheryl Walter, a lecturer in microbiology at the University of Hull in the United Kingdom, both viral vector and mRNA vaccines deliver the same information to human cells but do so in a different manner.

"One thing that the Pfizer and Moderna vaccines have in common with these approaches that use adenoviruses, is that they're delivering the same genetic information in the same format. So, it's not the message that might be causing these complications, it is most likely the adenovirus," Walter told Sputnik.

Walter said that further research needed to be done to identify the cause of the "casual link" between blood clot events and the AstraZeneca and Johnson & Johnson vaccines.

"Adenoviruses are very common, but we're also seeing it in these monkey adenoviruses, which of course, the vast majority of people would never have had exposure to. So right now, the short answer is no, we don't know what the cause could be," the University of Hull academic said.

Medical regulators have rushed to reassure members of the public that the risk of an individual developing blood clots after receiving a COVID-19 vaccine is far less than having the disease itself, or from taking the contraceptive pill or smoking.

According to a 2013 EMA report, between five to 12 cases of blood clotting events were reported in every 10,000 women who took hormonal contraceptives for a year, a higher incidence than that seen during the COVID-19 vaccine rollout.

"I do think a lot of work needs to be done to reassure people that the risk of a serious adverse event is far less than, for example, taking the [contraceptive] pill, or smoking, and that alternatives are being considered," University of Hull academic Cheryl Walter said.

Alice Pelton, the founder of the world's first review platform for contraception, The Lowdown, told Sputnik that the "uproar" created by the blood clot events linked to certain COVID-19 vaccines underlined the "ginormous double standards" in women's health.

"Not only is there a small increased risk of blood clots, but what about the other non-life threatening but life-impacting side effects millions of women experience on hormonal contraceptives? ... It's simply not OK that pharmaceutical companies don't have the time or money to improve a drug like 'the pill' that's been around for over 60 years and is used by over 150 million women worldwide," she said.

Walter said that the latest developments may result in greater numbers of younger people choosing not to receive the AstraZeneca COVID-19 vaccine in the United Kingdom, but added that the government should also ensure that these individuals have alternatives, such as mRNA vaccines.

"They might be looking at some of these statistics and saying 'well, I'd prefer not to take an adenovirus vaccine.' I think a lot of work needs to be done to rebuild their trust but also to provide alternatives for people who'd prefer to have alternatives," she said.

UCSF professor George Rutherford said that it was likely to be "difficult" to rebuild the public's trust in the AstraZeneca and Johnson & Johnson vaccines, but noted that in the state of California, the J&J vaccine accounted for only 4% of the allocation. The AstraZeneca vaccine has yet to receive emergency use approval in the United States.

Rutherford also said that there was very little risk tolerance for vaccines, in comparison to drugs to treat individuals with an illness or disease.

"There's almost no risk tolerance for vaccinations, except maybe the Ebola virus vaccine, but for a disease like this, there's almost no tolerance for risk," the UCSF professor said.

Researchers in the United Kingdom launched the so-called Com-Cov trial this past February, where participants receive different combinations of approved COVID-19 vaccines as part of their dosing regimen, which may pave the way for individuals to have greater choice over the vaccines they receive.

Commenting on the possibility of individuals receiving a mixed dosing regimen, WHO experts have so far said that they are waiting to receive more data and George Rutherford remarked that mixing doses result in individuals suffering "allergic reactions" or other severe side effects.

Rutherford also said that countries may be able to tailor their vaccination programs to ensure that current stocks of AstraZeneca vaccines are used in a safe and effective way.

"There's a lot of clamoring for vaccines, and if there is a way to avoid these complications, for instance not giving it to women at all, or not giving it to pre-menopausal women at all, then that might be a way to use the stock at hand to rebuild trust," he remarked.

The pace of vaccination across Europe shows no sign of slowing, after a shaky start, and European Commission President Ursula von der Leyen announced Wednesday that the bloc had reached the milestone of administering 100 million COVID-19 vaccine shots.

However, von der Leyen also announced that the EU was entering into negotiations with Pfizer/BioNTech for a third contract for an additional 1.8 billion COVID-19 vaccine doses for 2022 and 2023, in a sign that Brussels may look to phase out the AstraZeneca and Johnson & Johnson vaccines from its immunization program.

Sputnik V is currently being assessed as part of the EMA's rolling review process ahead of its potential approval for use within the bloc.