Is it the adenovirus vaccine technology, used by AstraZeneca and Johnson & Johnson, causing blood clots? There’s no evidence yet


Kylie Quinn, RMIT UniversityThis week, US health authorities recommended pausing the rollout of the one-shot Johnson & Johnson/Janssen COVID-19 vaccine while investigations into exceptionally rare blood clots take place.

Six women suffered blood clots out of nearly seven million doses administered.

The J&J vaccine uses broadly similar vaccine technology as the AstraZeneca vaccine, known as adenoviral vectors, which has led some experts to speculate there might be a link between this vaccine platform and the very rare blood clotting condition known as “vaccine-induced immune thrombotic thrombocytopenia” (VITT).




Read more:
What is thrombocytopenia, the rare blood condition possibly linked to the AstraZeneca vaccine?


So far, a link between adenovirus technology in general and blood clots is purely speculation — there’s no evidence yet — but it’s worthwhile for health authorities to assess the data and for researchers to try to understand:

  • can adenoviral vectors in general cause VITT?
  • is VITT specific to the AstraZeneca adenoviral vaccine?
  • are certain unlucky individuals pre-disposed to develop VITT?

So what’s an adenovirus, and how are they used in vaccines?

Adenoviruses are a large family of viruses found in humans and other animals. In humans, some of these viruses can cause the common cold.

Scientists can also use these viruses to make vaccines, by using them to make what’s called a “viral vector”. A vector is a virus shell that researchers can use to package up and deliver a target from another virus.

To make an adenoviral vector, scientists take an adenovirus and remove any genetic material that could either allow the virus to replicate and spread, or cause disease. Researchers then take the adenovirus shell and insert genetic instructions for how to make a target on the surface of another virus. For COVID-19, they use the instructions to make the “spike protein” on the surface of the SARS-CoV-2 virus.




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To your immune system, an adenoviral vector looks like a serious virus, even though it can’t replicate or cause disease. As a result, your immune system mounts a serious response, which is why people have been reporting more noticeable side-effects like a fever, fatigue and sore arm in the couple of days after the vaccine.

Similar but different

Currently, four COVID-19 vaccines use adenoviral vectors: AstraZeneca, Janssen/Johnson&Johnson, CanSino Biologicals and Sputnik V.

There are many adenoviruses out there to use as a starting point to make different adenoviral vectors. While these vectors can share some characteristics, they can also be biologically pretty different.

Different adenoviruses use different access points, known as receptors, to get into our cells. This can result in a very different size and type of immune response. Also, the adenovirus used in the Sputnik V and CanSino vaccines, called “rAd5”, isn’t very good at setting off the alarms in our immune system, while other adenoviral vectors are better.

The different vaccines also deliver slightly different sets of instructions for the spike protein. The J&J vaccine, called “rAd26”, instructs our cells to make a spike protein that’s locked into a specific shape, to help our immune system recognise it, and it’s delivered to the surface of the cell. The AstraZeneca vaccine, called “chAdOx01” instructs the cell to make a spike protein that isn’t locked in place and it can be secreted from the cell.

Given these differences, if one adenoviral vaccine is linked with a particular effect in our bodies, for example blood clots, it doesn’t mean all vaccines in this family will have that same effect. But regulators should still investigate.

We need to understand more about these blood clots

A number of regulatory bodies have issued notifications of a plausible link between the AstraZeneca vaccine and VITT.

This risk is very, very low — around one in 200,000 people that receive the vaccine could develop the condition. But for the rare person that develops VITT, the consequences can be serious, with around one-quarter of those with the condition dying from it. So regulators are taking the situation seriously.

VITT isn’t like other clotting conditions. There are many different types of clotting conditions but it seems VITT is likely to be caused by an unusual immune response.

We don’t know exactly what triggers this immune response. There have been reports of clotting conditions with adenovirus infections or very high doses of adenoviral vectors. However, this occurred very quickly, while VITT is a delayed response, observed 4-20 days after vaccination. It seems more likely at this stage that, in certain very rare patients, some kind of unusual immune response may be triggered.




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While researchers try to understand VITT, many regulators are taking a cautious approach — advising their communities, giving guidelines for preferred vaccines with younger age groups and revisiting data for other vaccines to be vigilant.

In doing this, regulators must balance a very rare risk of VITT with the AstraZeneca vaccine, with a very real risk of death and disease that face people with COVID-19. For many people, particularly older people in regions with community transmission of the virus, it still makes clear sense for their health to receive whichever COVID-19 vaccine is available.

These are complex decisions resulting in nuanced information that is hard to communicate. But the fact regulators are engaging with them quickly and transparently has been reassuring to me and, I hope, others in our broader community.The Conversation

Kylie Quinn, Vice-Chancellor’s Research Fellow, School of Health and Biomedical Sciences, RMIT University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

What is thrombocytopenia, the rare blood condition possibly linked to the AstraZeneca vaccine?


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Anthony Zulli, Victoria University; Maja Husaric, Victoria University; Maximilian de Courten, Victoria University, and Vasso Apostolopoulos, Victoria UniversityThe federal government has asked Australia’s medical and vaccine regulators to urgently consider the European Medicines Agency’s finding of a possible link between the Oxford/AstraZeneca COVID vaccine and rare blood clots.

This follows reports over recent weeks of blood clots in a small number of people around the world who had received the AstraZeneca vaccine, including one man who was hospitalised in Melbourne.

Scientists have termed the condition “vaccine induced prothrombotic immune thrombocytopenia” (VIPIT). But what does this actually mean, how significant is the risk, and what are the implications for Australia’s vaccine rollout — which is currently relying predominantly on the AstraZeneca jab?

A paucity of platelets

As indicated by its name, VIPIT is a form of something called thrombocytopenia.

Thrombocytopenia is a condition whereby the numbers of thrombocytes (very small blood particles, or platelets) are markedly reduced. Platelets form clots to stop bleeding, so when you don’t have enough platelets in your blood, your body can’t form clots. This can lead to excessive bleeding.

The condition has a genetic component, but can also arise from more than 300 common medicines, including penicillin and certain pain killers. Quinine, which is added to tonic water for flavour, can also very rarely cause thrombocytopenia.

The symptoms of VIPIT can include severe headaches, abdominal pain, seizures and visual changes. These are similar to the symptoms of thrombocytopenia unrelated to the vaccine.

In rare cases of thrombocytopenia, clots can develop in the vessels draining blood from the brain. The European Medicines Agency said it had received reports of 169 cases of brain blood clots in people who had been vaccinated with the AstraZeneca shot.

In severe cases, thrombocytopenia can be fatal. There have been deaths from blood clots reportedly associated with the AstraZeneca vaccine, including 19 in the United Kingdom.




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VIPIT appears to present 4-20 days after vaccination, and so far, the issue has been largely associated with women under the age of 65.

So how could this vaccine potentially cause thrombocytopenia? The “prothrombotic immune” part of the name denotes it’s caused by an over-activation of the immune system, which gives us a clue.

Platelets and COVID-19

The AstraZeneca vaccine prompts cells to make a specific part of SARS-CoV-2 (the virus that causes COVID-19), called the spike protein, which the virus uses to attach to cells when infecting us.

The vaccine stimulates our immune system to generate antibodies against the spike protein, which then primes the body to mount an immune response against SARS-CoV-2, if it encounters the virus in the future.

But in some people, the AstraZeneca vaccine seems to produce antibodies that react with platelets, making them stick together, leading the blood to clot. This in turn reduces circulating platelet numbers, and hence the thrombocytopenia.

These antibodies are similar to those found in some people on a blood thinning drug called heparin. The immune response to heparin generates antibodies that bind to platelets. This can lead to blood clots in some people, called heparin induced thrombocytopenia. As many as one in 20 patients receiving heparin develop thrombocytopenia.

Keeping in mind we’re yet to establish cause and effect, it’s a possibility that the biological mechanism by which we believe heparin leads to thrombocytopenia could be the same biological mechanism by which the AstraZeneca vaccine might.

How common is it?

Naturally occurring thrombocytopenia affects about one in 30,000 adults a year in the United States.

As for the suspected vaccine-induced kind, according to data collated by the Thrombosis and Haemostasis Society of Australia and New Zealand, VIPIT is as rare as one in 500,000 people. But the society notes the data are incomplete.

Different countries have reported different rates. Norway, for example, has so far reported one in 25,000 vaccinated adults under the age of 65 have experienced low platelet counts, bleeding, and widespread thromboses (blood clots).

Of course, the possibility that some of these cases of thrombocytopenia may have occurred regardless of the vaccine makes understanding vaccine-induced cases more complicated. But taken together, thrombocytopenia appears to be more common in the general population than among those who have been vaccinated.

As we continue to vaccinate the world, it’s likely small subsets of people will continue to experience this complication. Whether we can establish a causal link between the AstraZeneca vaccine and thrombocytopenia is subject to continued investigation.




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Be aware, but not alarmed

Amid this ongoing investigation, some countries, such as Norway, have paused their rollouts of the AstraZeneca vaccine. Others have restricted use of the vaccine in certain groups, like Canada, which is using it only for adults older than 55, who may have higher risks from COVID and lower risk of blood clots. Meanwhile, the UK has pledged to make other vaccine options available for younger people.

We will wait to see how the Australian experts respond. But for the general adult population, we agree with the current guidance from bodies including the European Medicines Agency and the World Health Organization that the benefits of the AstraZeneca vaccine outweigh the risks.

That said, it’s not unreasonable to be cautious. You should monitor for these symptoms up to 28 days after receiving the jab:

  • breathlessness
  • pain in the chest or stomach
  • swelling or coldness in the leg
  • severe or worsening headache
  • blurred vision
  • persistent bleeding
  • multiple small bruises, reddish or purplish spots, or blood blisters under the skin.

If you’re experiencing any of these symptoms and you’re concerned, seek medical advice.




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Data suggest no increased risk of blood clots from the AstraZeneca vaccine. Australia shouldn’t pause its rollout


The Conversation


Anthony Zulli, Associate professor, Victoria University; Maja Husaric, Senior Lecturer; MD, Victoria University; Maximilian de Courten, Professor in Global Public Health and Director of the Mitchell Institute, Victoria University, and Vasso Apostolopoulos, Professor of Immunology and Associate Provost, Research Partnerships, Victoria University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

AstraZeneca’s blood clot risk is incredibly small. Australia shouldn’t follow the UK’s lead of offering under 30s another vaccine


Nathan Bartlett, University of NewcastleAuthorities in the United Kingdom overnight recommended people under 30 be offered an alternative COVID vaccine to the AstraZeneca/Oxford shot.

The recommendation came after the European Medicines Agency (EMA) found a “possible link” between the vaccine and blood clots. The EMA also said blood clots should be listed as a “very rare” side effect of the vaccine.

It’s important to note there’s still no conclusive evidence the vaccine is causing the clots, as so few have been reported. However, evidence there is a link is increasing, which has prompted more focused monitoring.

The benefits of getting a COVID vaccine still far outweigh the risks. I would still be encouraging everyone to be vaccinated with the AstraZeneca vaccine.

Prime Minister Scott Morrison said this morning “there’s nothing to suggest at this stage that there would be any change” to Australia’s current rollout strategy. The Therapeutic Goods Administration and the Australian Technical Advisory Group on Immunisation are currently reviewing the data and latest advice from Europe and the UK.

What’s causing these clots?

Blood clotting events linked to vaccination are being called “vaccine-induced prothrombotic immune thrombocytopenia” (VIPIT).

In these rare instances, clots are forming in a patient’s blood, and not just in veins but in arteries and other rare locations like the brain and abdomen. This is also paired with low platelet counts (cells needed for the blood to clot).




Read more:
What is thrombocytopenia, the rare blood condition possibly linked to the AstraZeneca vaccine?


It appears, in these instances, the body’s response to the vaccine is triggering an “off target” immune response that is attacking platelets. Limited data that is yet to be peer reviewed suggests antibodies targeting platelets cause them to become activated and trigger clotting. This autoimmune response also targets the platelets for destruction, reducing their level in the blood. So platelets are either tied up in clots or are eliminated. Both processes contribute to “thrombocytopenia” (low blood platelet count).

Like infections, vaccines trigger an immune response, so when receiving any shot that stimulates a robust immune response there’s a small but real risk your immune system will generate “off target” effects. In these rare instances, these effects can lead to autoimmunity, which is an immune response that attacks your own cells.

All vaccines and medications come with small risks

The numbers of clots reported after the AstraZeneca are very small, so we don’t exactly know how common they are. But they appear to occur at a rate between one in 25,000 and one in 500,000.

The UK’s vaccine advisory board said there were 79 cases of blood clotting issues among more than 20 million people given the AstraZeneca vaccine. That’s a chance of about 0.0004%, or one in 250,000.

Researchers haven’t yet identified any specific risk factors so far for the development of blood clots following COVID vaccination. We need to understand as quickly as possible what these are if indeed a causal link is established.

Some have suggested there could be a link with women taking the contraceptive pill having a higher risk of blood clots after receiving the AstraZeneca vaccine. But there’s no evidence for this at all. As far as I know, information on whether women receiving the vaccine are taking the contraceptive pill isn’t captured. Perhaps it’s something to consider going forward.

Young people don’t appear to be at particularly higher risk of blood clots linked to the vaccine. The publicised cases of blood clots have occurred in mostly women under 60 years of age.

Australia shouldn’t follow the UK’s new recommendation

One reason the UK is able to advise younger people to receive other vaccines is because it has other vaccine options, including the Pfizer and Moderna shots. Offering the under 30s an alternative vaccine isn’t really going to hinder the rollout, which is going very well in the UK.

But this isn’t the case in Australia. The AstraZeneca shot is the only one we have guaranteed supply of, given CSL is producing it in Melbourne.

It’s important to remember the AstraZeneca vaccine is a very safe and effective vaccine. It’s also easier to store and distribute than the Pfizer vaccine.

The priority is vaccinating as many people as possible and quickly

It’s important to note we’re in uncharted territory. This is the first time in modern history we’ve been in a situation where we’ve needed to roll out a vaccine to deal with a pandemic.

We’re also using new vaccine technologies that we’ve had to expedite to try and get on top of this virus as soon as possible. These new technologies, including AstraZeneca’s, have never been tested at this immense scale until now.

There are a lot of unknowns, but certainly the scale in which were doing this means we’re going to see very rare adverse events linked to these vaccines.

At this stage the priority is still to vaccinate as many people as possible, as quickly as possible.

My primary concern is ongoing high levels of transmission across the world. The more cases there are, and longer we delay vaccinating people, the higher the likelihood is of new variants of the virus emerging.




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Even though we have very low COVID-19 case numbers in Australia currently, we’ve seen regular outbreaks stemming from hotel quarantine. We can’t predict what’s going to happen in the future. The longer the virus is waiting at our doorstep, the greater the risk we’ll have another outbreak and end up in lockdown and much worse — and nobody wants that.The Conversation

Nathan Bartlett, Associate Professor, School of Biomedical Sciences and Pharmacy, University of Newcastle

This article is republished from The Conversation under a Creative Commons license. Read the original article.

People with coronavirus are at risk of blood clots and strokes. Here’s what we know so far



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Karlheinz Peter, Baker Heart and Diabetes Institute; Hannah Stevens, Baker Heart and Diabetes Institute, and James McFadyen, Baker Heart and Diabetes Institute

As well as causing severe respiratory problems, there is mounting evidence COVID-19 causes abnormalities in blood clotting. Patients with severe COVID-19 infection appear to be at greater risk of developing blood clots in the veins and arteries.

Blood clots can occur deep in the veins of the leg (deep vein thrombosis) and can move to the lungs, causing a pulmonary embolism, which restricts blood flow and oxygen, and can be fatal.




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Blood clots in arteries can cause heart attacks when they block blood supply to the heart, or strokes when they block oxygen supply to the brain.

So what is going on in the bodies of people with coronavirus? And what are clinicians doing to treat or prevent this complication?

What do these clots do?

Recent data from the Netherlands and France suggest that of the patients with coronavirus who are admitted to intensive care units (ICU), 30-70% develop blood clots in the deep veins of the legs, or in the lungs.

Around one in four coronavirus patients admitted to ICU will develop a pulmonary embolism.

These rates are much higher than we would usually see in patients requiring admission to ICU for reasons other than COVID-19.

Greater risk of stroke

Patients who present to hospital with COVID-19 are also more likely to have a stroke when compared with the general population.

Typically, the chance of having a stroke is associated with increasing age, as well as other risk factors such as high blood pressure, elevated cholesterol levels, or smoking.

Usually it’s older people who have strokes.
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However, higher rates of strokes in patients with COVID-19 is somewhat unusual because it also seems to be happening in people under 50 years of age, with no other risk factors for stroke.

Low levels of oxygen

COVID-19 also appears to be associated with blood clots in the tiny blood vessels that are important for the transfer of oxygen in organs. Autopsy reports have shown elements of SARS-CoV-2, the virus causing COVID-19, in cells lining these small blood vessels in the lungs, kidney, and gut.

This may result in tiny blood clots in these small blood vessels that disturb normal blood flow and the ability of the blood to deliver oxygen to these organs.




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Importantly, these small blood clots could reduce normal lung function. If these small blood clots reach the lungs it may prevent oxygen getting into the blood as efficiently as normal. This may explain why patients with severe COVID-19 can have very low oxygen levels.

Treating and diagnosing clots is difficult

When patients are admitted to hospital, for coronavirus or any other condition that leaves them bed-bound, it is common practice to administer low-dose blood thinners to prevent the development of blood clots.

However, given that patients with COVID-19 seem to be at a higher risk of developing blood clots, it’s currently being debated whether higher doses of blood thinners are required to prevent these clotting complications.

Trials are underway to attempt to answer this important question.

Higher doses of blood thinners might one day play a role in treating COVID-19.
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Diagnosing these blood clots in patients with COVID-19 can also be particularly challenging.

Firstly, the symptoms of a worsening lung infection associated with the virus can be indistinguishable from the symptoms of a pulmonary embolism.

Another challenge in COVID-19 is that the virus can impact laboratory tests which may also be used to diagnose venous blood clots.

A good example of this is a test called D-dimer, which is a measure of clotting in the body. Normally, this test would be higher in almost everyone with new venous blood clots. However, people with severe COVID-19 infection can also have an elevated D-dimer simply due to the severe infection.

In some patients, this means that the test is no longer helpful to diagnose blood clots.

Why does COVID-19 cause blood clotting?

One theory is that the increased rate of blood clots in COVID-19 is simply a reflection of being particularly unwell and immobile.

However, the current data suggest the risk of blood clots is significantly greater in patients with COVID-19 than what is usually see in patients admitted to hospital and ICUs.

We still don’t know why clotting occurs.
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Another potential explanation is that the virus is directly impacting on the cells lining our blood vessels. When the body fights an infection, the immune system becomes activated to try and kill the invader, and research shows an activated immune system can cause blood clots.

In severe COVID-19, the immune system appears to go into overdrive. This could lead to the unchecked activation of cells that typically stop blood clotting.




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Another possibility is that the virus triggers blood clotting to provide it with a survival advantage.

The SARS virus, another member of the coronavirus family, can be further “activated” by a blood clotting protein, enabling the virus to more efficiently invade cells.

However, whether this is the case with COVID-19 remains to be investigated.

Intriguingly, preliminary research suggests that a commonly used blood thinner, heparin, may have antiviral effects by binding to SARS-CoV-2 and inhibiting a key protein the virus uses to latch onto cells.

What we know for sure is that blood-clotting complications are rapidly emerging as a significant threat from COVID-19. In this area, we still have much to learn about the virus, how it affects blood clotting, and the best options for prevention and treatment of these blood clots.The Conversation

Karlheinz Peter, Lab Head, Atherothrombosis and Vascular Biology and Deputy Director, Baker Heart and Diabetes Institute; Interventional Cardiologist, Alfred Hospital; Professor of Medicine and Immunology, Monash University, Baker Heart and Diabetes Institute; Hannah Stevens, Haematologist and PhD student, Baker Heart and Diabetes Institute, and James McFadyen, Research Fellow, Baker Heart and Diabetes Institute, Haematologist, Alfred Hospital, Baker Heart and Diabetes Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.