The COVID vaccines have rare – but serious – side effects. Based on 21 million vaccinated Australians (and 5.6 billion globally) we can base our calculation of benefit versus risk on hard numbers. (See rollout risk versus benefit.)
But some of my vaccine-hesitant friends are getting alarmed by a very fluffy set of figures.
These are the adverse effects that are reported following immunisation. From January to August of this year, 52,849 events and 476 deaths have been recorded in the publicly accessible Database of Adverse Event Notifications (DAEN). This database has captured a huge number of events – because Australia is extremely vigilant about monitoring the vaccinated.
Those on sentry duty feel their responsibility keenly. As paediatric immunologist Kristine Macartney, director of the National Centre for Immunisation Research and Surveillance (NCIRS), explained to me, Australia had ramped up its vigilance in the last 10–15 years after some batches of flu vaccines caused extremely high fevers in children, while others were potentially linked to an increase in Guillain Barre Syndrome (more on GBS shortly).
In the 2000s, the system relied on doctors to tick the boxes against a checklist of predicted side effects. Now the limited checklist is gone and the net has been cast much wider. “Our message to the doctors is report, report, report,” says Macartney.
As well as capturing information from GPs, NCIRS established a fully automated surveillance system that sends out texts to people three days after vaccination to ask them about side effects. It’s known as AusVaxSafety – and so far it’s received 2.4 million replies. Self-reporting is not as accurate as a doctor’s report, but the trigger for AusVax to follow up is if there’s been a hospitalisation, says Macartney. These data also give valuable information about people who aren’t experiencing any issues – something missing from the doctors’ reports. A third arm of vaccine surveillance sweeps across hospitals.
With such a fine-meshed and widely cast net, it’s inevitable that events that have nothing to do with the vaccine will be captured. Indeed the database reads like a laundry list of every malady known to woman or man, including one report of foaming at the mouth, another of hair loss and a third of painful erections. Just what you’d expect if you care to ask about the health of more than 10.9 million people (as of 22 August) who have received their first dose. Vaccination against COVID certainly doesn’t make other ailments disappear.
And people will still die in the period after getting vaccinated. Some deaths clearly have nothing to do with the vaccine, for instance those occurring in late-stage cancer patients, or those with severe heart disease.
But then there are grey areas.
So how do you decide what is related to the vaccine and what is sad coincidence?
That’s where the Therapeutic Goods Authority (TGA) comes in. Like detectives at the scene of a crime, their job is to trawl through the 54,000 suspects caught in the net.
TGA head John Skerritt described to me the tools his team uses to pare away the bystanders from the true culprits.
For starters, they check the background rate of certain ailments. For instance, as younger women have become eligible for vaccines, the database has captured reports of heavy menstrual bleeding. So far, says Skerritt, analyses show that these reports are not higher than the background rate – heavy menstrual bleeding is reported as a common problem affecting 25% of women of reproductive age.
Similarly ‘ordinary’ blood clots are not infrequent – some 17,000 are reported in Australia each year, 46 each day. So it’s no surprise that many of those receiving Astra, who tend to be older people, would present with a blood clot in the weeks after vaccination. Haematologist Huyen Tran, who heads the Thrombosis and Haemostasis Unit at the Alfred Hospital in Melbourne, is confident that these cases are not linked to the vaccine.
It’s the unusual cases that alert the TGA to follow up, especially if the symptoms have a clear biological link to the immune system, and if they occur within four weeks of vaccination. (According to the WHO, most vaccine-related events occur within a month of vaccination as the immune system is mobilising its forces.) To trawl through the list of possible suspects, the TGA assembles a detective team composed of statisticians and medical specialists to interrogate the medical history of each patient.
TTS blood clots
A clear-cut case of a vaccine-related adverse effect is thrombosis with thrombocytopaenia syndrome, or TTS, first reported in the UK in March after the mass rollout of the Astra vaccine.
Blood clots are not unusual – they occur in about 1 in 1000 people each year. But mostly they occur in older people and in the legs or lungs.
TTS clots are highly unusual. They were occurring in people under 40 (where the normal rate is about 1 in 10,000 per year), and in unusual places: in the brain (cerebral vein) or the intestine (splanchnic vein). And besides excessive clotting (thrombosis), these people were also experiencing excessive bleeding (thrombocytopenia).
As of 9 September, the TGA detective team has picked up 132 of TTS cases out of 10.2 million Astra vaccine doses. There have been 8 deaths. So the average risk of contracting TTS is around 1.3 in 100,000. The risk of death is less than one in a million. The risk of dying from COVID is 1 in 100. (See rollout risk versus benefit.)
Occasionally the TGA are faced with borderline cases. The 22 August COVID-19 vaccine weekly safety report described five mild cases of thrombosis with thrombocytopaenia syndrome, or TTS, in older people that were associated with a second shot of the Astra vaccine.
An independent group that included experts in infectious disease, vaccinology, haematology, respiratory medicine, immunology and public health was called in to review these cases.
The panel were able to clearly dismiss the vaccine as the cause of two cases and were dubious about the other three. However, according to the report, “further testing to clarify this is underway and an update will be provided once test results are available”.
The tone of the report illustrates the fine-toothed comb that is being run along the reported cases. “I don’t think we’re missing much, we have excessive awareness,” says Tran.
Guillain Barre Syndrome
While most TTS cases stand out like a sore thumb, other suspects are much more difficult to confirm as true signals above the noise.
Guillain Barre Syndrome has long represented an unsolved problem when it comes to vaccines. It is a creeping paralysis of the peripheral nervous system, usually starting from the toes up. In severe cases, people can end up on a respirator. But for 75–90% of cases, the effects are temporary.
Vaccines aside, GBS typically crops up in people a few weeks after they’ve recovered from a viral infection. After fending off the virus, the immune system mistakenly directs its fire against the myelin sheath of peripheral nerves. Mercifully that friendly fire is rare: GBS occurs at a background rate of about 1.7 in 100,000 people and is more common in flu season.
The unsolved question is: can that friendly fire also be elicited by vaccination? In 1976 in the US after a rollout of swine-flu vaccinations, public health authorities saw a slight increase of a further 1 in 100,000 above the background rate. Ever since, health authorities scrutinise GBS numbers after every new vaccine, says neurologist and GBS expert Geoffrey Herkes, at Sydney’s Royal North Shore Hospital.
Up to 5 September, the TGA has received 110 reports of GBS associated with 10.2 million shots of the Astra vaccine This equates to 1.1 in 100,000. No one is really sure if this is a true signal above the noise.
As the weekly TGA safety bulletin puts it: “Following an investigation, the TGA, along with other international drug regulators, have so far been unable to establish a clear link between GBS and Vaxzevria (AstraZeneca).”
Herkes says the data from the UK, which has delivered far more Astra vaccines than Australia, suggests the maximum possible increased risk could be one extra case per 100,000. “Coincidence or not, this is not a reason to panic about getting an Astra shot,” says Herkes.
YOUR COVID TOOLBOX: This article is one of a five-part series where Cosmos editor-at-large Elizabeth Finkel hunts down all the facts and figures you need to understand COVID-19 vaccines.
Elizabeth Finkel is editor-at-large of Cosmos.
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