Rogue antibody and mystery pathogen behind AstraZeneca blood clots: study
A rare gene combined with exposure to a mystery pathogen may have caused the blood clotting issues that plagued AstraZeneca’s COVID-19 vaccine.
Australia pinned much of its COVID-19 response strategy on AstraZeneca’s vaccine, with 50 million doses produced by CSL’s Broadmeadows plant.
But at the height of the pandemic last year, as millions of Australians were preparing to roll up their sleeves, the vaccine was linked to an extremely rare but deadly blood clot disease.
It left many with a tough choice: get jabbed and take the three-in-100,000 risk of clots, or decline the vaccine and take your chances with the virus. In total, 173 Australians suffered clots, and eight people died.
Exactly what caused the clots has remained a mystery. But this month a team of Australian scientists led by Flinders University’s head of immunology Professor Tom Gordon reported in the journal Blood that they had traced the culprit down a single gene – and a mystery pathogen.
“This was very unusual,” Gordon said. “In 35 years of looking at blood autoantibodies I have never seen anything like this.”
AstraZeneca’s vaccine is built around an adenovirus vector – a harmless virus modified to carry the genetic code of COVID-19’s spike protein.
After vaccination, the virus infects our cells, which then use the genetic code to produce copies of the spike protein. In turn, our immune system learns to recognise the spike and builds an arsenal of antibodies designed to fight it.
But scientists suspect the adenovirus itself can accidentally bind to a crucial natural protein in the body known as PF4. A small signalling molecule, it’s used to get blood to thicken – important in repairing cuts, for example.
In rare cases, people develop antibodies that can recognise and bind to this combination of adenovirus and PF4. By binding, the antibodies activate PF4, causing it to signal platelets in the blood to clump together.
“Once you clump platelets you get widespread clotting. So they are exceptionally dangerous,” Gordon said.
But that explanation leaves a gaping hole. We all have PF4. Why did only a few people get clots?
A rogue antibody
Working with rogue antibody samples from five people in Adelaide who suffered clots after the vaccine – including one person who died – Gordon’s team made several key discoveries.
First, they discovered the rogue antibodies slotted perfectly into a groove on PF4 that was only exposed when PF4 was exposed to AstraZeneca’s adenovirus.
Then they found the antibodies from the five people were almost identical.
Antibodies vary a lot from person to person; the immune system can make perhaps a million trillion unique types. Pulling identical antibodies from five unrelated people is extremely rare and suggests genes are playing a role.
Genetic sequencing revealed each patient was expressing a gene known as IGLV3-21*02, which was likely responsible for the unique antibody.
Case closed? Not quite.
About four people in every 100 have IGLV3-21*02, but the risk of clotting from AstraZeneca’s vaccine was a fraction of that. Something more must have been going on.
The final clue was hidden in the disease’s speed. It can take weeks for antibodies to be generated to a new virus, but some people suffered clotting just days after getting vaccinated. That suggested, Gordon said, their immune systems had already experienced this strange combination of adenovirus and PF4 – or something that looked a lot like it.
“How can it be? We don’t know. That’s one of the great mysteries,” he said.
Professor James McCluskey, an expert on the genetics of immunity and a deputy vice-chancellor of the University of Melbourne, called the study “rather remarkable”.
“Antibody genes … can vary genetically from one individual to another. For all these patients to have the same [gene] is just intuitively improbable by chance. So it looks real,” he said.
AstraZeneca’s vaccine remains in use in Australia, but official health advice is to opt for Pfizer or Moderna if you’re under 60. But AstraZeneca continues to be distributed, particularly in low-income countries.
Gordon hopes his study will open up new ways to either test people for genetic susceptibility to the condition or design medicines to treat it.
Gas crackdown already halting new investments
Future gas and LNG projects valued at $32bn are under threat of having investment stalled or pulled under the Albanese government’s “hostile attitude to Australia’s resources sector” after the Gina Rinehart-backed Senex paused its $1bn Surat Basin expansion project.
Up to 12 gas projects listed in the government’s resources and energy major projects investment pipeline report on Monday are considered to be facing “significant uncertainty” following the government’s crackdown on gas companies.
Amid industry concerns over the government’s one-year $12-a-gigajoule gas price cap, mandatory code of conduct on gas producers and tougher environmental approval regulations, there are rising fears that other companies could suspend projects.
Senex’s decision to halt work on its coal seam gas projects is the latest hit to Queensland’s resources industry, where coalminers Glencore and BHP have shelved or frozen investment amid a running brawl with the state’s Labor government over a shock royalty hike announced in its July budget.
Opposition resources spokeswoman Susan McDonald said “more than $15bn in future east coast gas projects are under a cloud of uncertainty due to Labor’s hostile attitude towards Australia’s energy resources sector”.
Nine projects planned to supply east coast domestic gas, and another three LNG projects that could supply gas to the east coast, are valued at $32bn.
Senex, jointly owned by POSCO and Ms Rinehart’s Hancock Energy after they sealed a $900m takeover of the ASX-listed company in March, announced the $1bn coal seam expansion project four months ago around the same time the federal government was drafting its plans to combat high domestic gas prices.
The coal seam expansion was aimed at pumping more gas into the domestic market by lifting its Atlas project to 60 petajoules within two years.
Senex has left open the possibility of returning to the $1bn expansion if the federal government rethinks its gas industry plans. However, it has paused recruitment and spending on long lead items “pending the outcome of the Albanese government’s mandatory code of conduct consultation process” on February 7.
A spokesman for Resources Minister Madeleine King said the government was “confident Senex will continue to engage constructively with the government as they design and implement the gas code of conduct”. He said the government’s gas price cap applied only to existing projects and not “new projects like Atlas”.
“The government wants to design a measure that does not have a chilling effect on investment, and ensures investment continues to flow to new products,” Ms King’s spokesman said.
“The gas code of conduct, once it enters into force, is not about stripping profits off producers. It’s about ensuring that where gas enters the domestic market, Australian households and businesses are not subject to the exponentially skyrocketing prices that we have seen throughout the course of this year. “That’s not on, and the code will prevent those runaway prices that we have seen previously.”
Acting Treasurer Katy Gallagher this week authorised the gas price cap to begin from Friday, with the Australian Competition & Consumer Commission tasked with “closely monitoring” the east coast gas market and enforcing the cap.
Senator Gallagher said without capping gas and coal prices, “the average family would be paying $230 more on their electricity bill next year”.
Senator McDonald said the government was “joining forces with the Greens to implement unprecedented price controls, hand over more power to unions, increase environmental red-tape and fund anti-mining lawfare groups”.
“Coal and gas alone are forecast to earn Australia $223bn but under Labor’s war on conventional energy commodities, 18 coal and gas projects have been reopened for environmental assessment after already receiving approval, and 43 oil and gas projects have been required to redo their consultation,” Senator McDonald said.
“Our regional partners, like Japan and Korea, will be very concerned about Australia’s approach to providing the energy commodities they need to power their economies. All this sends strong signals to international companies that they are not welcome here, so we can expect them to consider halting their investment.”
Liberal Senator Paul Scarr says “basic economics” is all it takes to realise imposing gas price caps at “less than… the market-prevailing price” will create a shortage of investment and, consequently, energy reserve. “It’s an investment-killing concoction,” Mr Scarr told Sky News host Gary Hardgrave. “The consequences are disastrous, especially More
In the government’s major projects report, prepared before the national cabinet slapped a $125-a-tonne price cap on coal, 33 coal projects were stalled in the feasibility stage as lenders and investors, led by pension and equity funds, pull finance for thermal coal projects.
Global mining giant Glencore earlier this month pulled the plug on plans to build its $2bn Valeria thermal coalmine, citing Queensland’s royalty rate increase as a major cause. BHP is also considering the impact of the royalty rate hikes on the life of its Queensland coal operations.
The mining giant has already said it will not invest in Queensland growth projects while the windfall royalty rates are in place, and set aside $US750m in its annual financial accounts for potential early closure and rehabilitation costs.
Australian Petroleum Production & Exploration Association chief executive Samantha McCulloch said the Senex decision highlighted risks involved with the Albanese government’s gas market intervention.
“No new gas supply means no downward pressure on prices and an increased risk of future gas shortages,” Ms McCulloch said.
“Without this kind of investment, Australia misses out on crucial new gas supply to ease east coast energy system pressures as well as substantial economic returns including hundreds of jobs and hundreds of millions of dollars of local investment in regional communities.”
Opposition treasury spokesman Angus Taylor said market interventions were “adding to red tape and complexity for investors both domestically and abroad”.
“The billions of dollars of projects on hold or under question shows that when we are in a global race for capital, more regulation leads to less investment, which means fewer jobs, less work for small businesses and a slower economy,” Mr Taylor said.
After the Office of the Chief Economist on Monday revealed that resources and energy export earnings will fall by $68bn in 2023-24, down from a record $459bn this financial year, Mr Taylor said it was imperative for the budget bottom line to avoid future slides.
“This makes it all the more alarming that the government is cutting funding support for our resources sector and making extreme interventions that energy experts are warning will cool investment and decrease supply,” he said.
RBA warning: Our supply-side problems have only just begun
In one of his last speeches for the year, Reserve Bank governor Dr Philip Lowe has issued a soberingwarning. Even when we’ve got on top of the present inflation outbreak, the disruptions to supplywe’ve struggled with this year are likely to be a recurring problem in the years ahead.
Economists think of the economy as having two sides. The supply side refers to our productionof goods and services, whereas the demand side refers to our spending on those goods and services, partly for investment in new production capacity, but mainly for consumption by households.
Lowe notes that, until inflation raised its ugly head, the world had enjoyed about three decades inwhich there were few major “shocks” (sudden big disruptions) to the continuing production and supply of goods and services.
When something happens that disrupts supply, so that it can’t keep up with demand, prices jump –as we’ve seen this year with disruptions caused by the pandemic and its lockdowns, and withRussia’s attack on Ukraine.
What changes occurred over the three decades were mainly favourable: they involved increasedsupply of manufactured goods, in particular, which put gentle downward pressure on prices.
This made life easier for the world’s central banks. With the supply side behaving itself, they wereable to keep their economies growing fairly steadily by using interest rates to manage demand. Putrates up to restrain spending and inflation; put rates down to encourage spending and employment.
What’s got Lowe worried is his realisation that a lot of the problems headed our way will be shocks to supply.
The central banks were looking good because the one tool they have for influencing the economy –interest rates – was good for managing demand. Trouble is – and as we saw this year – managing demand is the only thing central banks and their interest rates can do.
When prices jump because of disruptions to supply, there’s nothing they can do to fix those disruptions and get supply back to keeping up with demand. All they can do is strangle demand until prices come down.
So, what’s got Lowe worried is his realisation that a lot of the problems headed our way will be shocks to supply.
“Looking forward, the supply side looks more challenging than it has been for many years” and is likely to have a bigger effect on inflation, making it jump more often.
Lowe sees four factors leading to more supply shocks. The first is “the reversal of globalisation”.
Over recent decades, international trade increased significantly relative to the size of the global economy, he says.
Production became increasingly integrated across borders, and this lowered costs and made supply very flexible. Australia was among the major beneficiaries of this.
Now, however, international trade is no longer growing faster than the global economy. “Trading blocs are emerging and there is a step back from closer integration,” he says. “Unfortunately, today barriers to trade and investment are more likely to be increased than removed.”
This will inevitably affect both the rise in standards of living and the prices of goods and services inglobal markets.
The second factor affecting the supply side is demographics. Until relatively recently, the working-age population of the advanced economies was steadily increasing. This was also true for China andEastern Europe – both of which were being integrated into the global economy.
And the participation of women in the paid labour force was also rising rapidly. “The result was asubstantial increase in the number of workers engaged in the global economy, and advances intechnology made it easier to tap into this global labour force,” Lowe says.
So, there was a great increase in global supply. But this trend has turned and the working-agepopulation is now declining, with the decline projected to accelerate. The proportion of thepopulation who are either too young or too old to work is rising, meaning the supply of workersavailable to meet the demand for goods and services has diminished.
The third factor affecting the supply side is climate change. Over the past 20 years, the number ofmajor floods across the world has doubled and the frequency of heatwaves and droughts has alsoincreased.
This will keep getting worse These extreme weather events disrupt production and so affect prices – as we know all too well in Australia. But as well as lifting fruit and vegetable prices (and meat prices after droughts break and herd rebuilding begins), extreme weather can disrupt mining production and transport and distribution.
The fourth factor affecting the supply side is related: the transition from fossil fuels to renewables. This involves junking our investment in coal mines, gas plants and power stations, and new investment in solar farms, wind farms, batteries and rooftop solar, as well as extensively rejigging the electricity network.
It’s not just that the required new capital investment will be huge, but that the transition from the old system to the new won’t happen without disruptions.
So, energy prices will be higher (to pay for the new capital investment) and more volatile when fossil-fuel supply stops before renewables supply is ready to fill the gap.
Lowe foresees the inflation rate becoming more unstable through two channels. First, shocks to supply that cause large and rapid changes in prices.
Second, the global supply curve becoming less “elastic” (less able to respond to increases in demand by quickly increasing supply) than it has been in the past decade.
Lowe says bravely that none of these developments would undermine the central banks’ ability to achieve their inflation target “on average” - that is, over a few years – though they would make the bankers’ job more complicated.
Well, maybe. As he reminds us, adverse supply shocks can have conflicting effects, increasing inflation while reducing output and employment. The Reserve can’t increase interest rates and reduce them at the same time.
As Lowe further observes, supply shocks “also have implications for other areas of economic policy”. Yes, competition policy, for instance.
Low-fee private schools rival expensive counterparts in HSC
At Alpha Omega College, a co-ed school in a suburban office block, students don’t wear uniforms, teachers are called by their first names and there is no bell to round up pupils to class.
“It’s not a normal school,” says deputy principal Wesam Krayem. “We do things differently and it makes students feel like there are fewer barriers. We also open the school on weekends and holidays for extra tutoring sessions.”
The western Sydney college is one of multiple lower-fee private schools across NSW that had similar — or better — HSC success rates than schools where fees tip over $20,000 a year, a Herald analysis has found.
Catholic schools that charge fees of about $6000 a year or less — including Randwick’s Brigidine College, Hurstville’s Bethany College and Parramatta Marist High — had a similar or a higher portion of students achieving band-six HSC results as St Joseph’s in Hunters Hill and the Scots College in Bellevue Hill, where parents pay about $40,000 for year 12.
St Clare’s College in Waverley — which charges about $7000 for year 12 — was the highest-ranked systemic Catholic school at 31st out of the 143 top private schools analysed, based on the past two years of HSC results. It had a success rate similar to Barker College and St Ignatius College Riverview, where final-year fees are more than $32,000.
Former chair of NSW Education Standards Authority Tom Alegounarias said fees did not necessarily correlate with consistently high academic performance.
“Results likely reflect all sorts of dynamics beyond the socio-economic backgrounds of students. It could be about the relative effectiveness of the school, and if there is healthy competition among staff and students. Schools might be focusing on academic achievement and the rigours that are needed to get those results. Band sixes are also only one indicator, and are not a reliable indicator of range achievement in schools,” Alegounarias said.
At Auburn’s Alpha Omega College there is an intense focus on academic results and a strict no mobile phone policy for the 500-odd students at the school.
“There is a ‘never give up attitude’ ... students get constant feedback on how they are going. The school is open on some weekends for study groups and algebra workshops,” said Krayem. Parents pay about $13,000 for year 12 at the school.
The Herald’s analysis compared fees with HSC success rates — the ratio of band six results at a school compared to the number of students that sat exams. It used this year’s fees published on school websites, and if these weren’t available took the most recent fees and charges reported or used data from the Australian Curriculum, Assessment and Reporting Authority to estimate fees.
Authorities only release the names and schools of students who achieve in the top band of their subject. Private school sectors have previously suggested the NSW government release more data to reflect the efforts of all students, not just the top achievers.
Fees at Al Noori Muslim School in Greenacre and Al Faisal College are roughly $3000 a year, and those schools had a similar portion of students in the top HSC bands as Knox Grammar and Kincoppal Rose Bay.
Chief executive of Catholic Schools NSW Dallas McInerney said the sector aimed to provide choice for parents through a system of low-fee comprehensive schools.
“HSC results do not account for socio-economic background, fees or enrolment policy, therefore the results of these schools and students are really an against-the-odds story,” he said.
‘We set the bar high’: How Reddam House blitzed HSC maths
Robyn Rodwell, the principal of Catholic systemic school Bethany College, said the school had high expectations of the girls.
“Before we teach a new topic we do pre-testing to find out what they already know, and that way after we’ve taught the unit you can see how much they’ve grown. We also invest in really solid teacher development programs,” she said.
Head of the Association of Independent Schools of NSW Geoff Newcombe said the median fee collected for private schools in NSW was around $5200 a year. “These schools are not selective, and their regular success reflects the commitment of the students, their families, teachers and principals to strong academic outcomes at all levels.”
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