COVID-19 vaccine weekly safety report - 15-07-2021

The most common adverse effects following immunisation reported to the TGA are predictable and have been observed with vaccines generally. They include headache, muscle pain, fever, chills and injection site reactions.

The most common reactions reported for the AstraZeneca COVID-19 vaccine in the week of 5-11 July 2021 were headache, fever, muscle pain, fatigue and chills.

The most common reactions reported for the Comirnaty (Pfizer) COVID-19 vaccine in the week of 5-11 July 2021 were headache, muscle pain, lethargy, injection site reactions and nausea.

Adverse events reported for Aboriginal and Torres Strait Islander people

When someone reports a suspected side effect to the TGA, we ask them to include patient ethnicity on the reporting form to help us identify any differences between particular populations. Almost half of the reports include this information which gives us a useful indication of vaccine safety in different populations. We previously reported that only 20% of reports included ethnicity, but this has been revised to almost 50% following further analysis of our data.

Since the beginning of the vaccine rollout to 11 July 2021, the reporting rate of side effects following vaccination of Aboriginal and Torres Strait Islander people is 2.5 reports per 1000 vaccine doses. The nature of the side effects reported for Aboriginal and Torres Strait Islander people are similar to the total population with the most common being headache, muscle pain, fever, nausea and lethargy.

Based on the information reported to the TGA, none of the TTS cases so far has been identified as being in an Aboriginal or Torres Strait Islander person.

Further information on adverse event reports in Aboriginal and Torres Strait Islander people is published in the ongoing AusVaxSafety survey.

Interpreting information on vaccine adverse event reports

We are aware that false claims are circulating based on misinterpretation of adverse event information published by medicine regulators. To improve transparency, the TGA makes adverse event reports publicly available 90 days after they are received in the Database of Adverse Event Notifications (DAEN). Similar information is published by other regulators overseas. When interpreting this information, it is important to understand that many of these events may not be caused by vaccine.

The TGA encourages reporting of adverse events even if people are uncertain or only suspicious that it is related to a vaccine or medicine. This supports our scientists and health professionals to use the data to look for new safety signals. Reporting of adverse events, such as the death of anyone who has received a vaccine, is mandatory for health professionals in some states, even if they know it is unrelated to immunisation. It is therefore important to remember that the number of adverse events and deaths is not an indicator of the safety of the vaccines. Detailed investigation and expert review of individual case reports and the data as a whole are required to assess whether there is a link between an event and the vaccine.

It is important when looking for information about COVID-19 vaccines to consider whether the source of the information is credible. Useful websites such as ‘COVID vaccines – is it true?’ help to debunk false claims and misleading rumours. Other reliable resources are listed at the end of this report.

Latest recommendations from the Australian Technical Advisory Group on Immunisation (ATAGI)

In light of a significant COVID-19 outbreak involving the Delta variant in Australia, ATAGI have reviewed their advice on use of COVID-19 vaccines. Their latest statement, published on 13 July 2021, states that recommendations are unchanged and that Pfizer’s Comirnaty vaccine is preferred over the AstraZeneca vaccine for those aged 16–60 years old. The statement reinforces that the benefits of the AstraZeneca vaccine strongly outweigh the risks for people aged 60 and over and given the current outbreak vaccination is essential in this group.

Now we are in an outbreak situation and the risk of catching COVID-19 is higher, ATAGI urges younger Australians who may not be able to get vaccinated immediately with Comirnaty to re-assess whether to get the AstraZeneca vaccine. This should consider the protective benefits of vaccination to themselves and their contacts who may be more vulnerable to serious disease or death from COVID-19.

ATAGI also recommends getting the second AstraZeneca dose within 4–8 weeks after the first dose, rather than waiting 12 weeks, so full protection can be reached sooner.

More details are given in the full ATAGI statement.

AstraZeneca COVID-19 vaccine

Reports of side effects to the AstraZeneca vaccine continue to be generally consistent with what is being observed internationally. Most are expected side effects that we know occur after vaccination and resolve within a few days. To 11 July 2021, approximately 5.4 million doses of the AstraZeneca COVID-19 vaccine have been administered.

Thrombosis with thrombocytopenia syndrome (TTS)

The TGA and other international medicines regulators continue to closely monitor and investigate TTS. This is a rare event involving serious blood clots with a low blood platelet count. It is triggered by the immune system’s response to the AstraZeneca vaccine and is different from other clotting conditions.

The latest reporting rates of TTS in Australia were published in a statement from ATAGI on 8 July 2021.

While TTS is very rare, some people may have concerns that they can discuss with their doctor. This is essential to allow people to make an informed choice about vaccination. 

People should seek immediate medical attention if they develop any of the following symptoms after vaccination:

• severe or persistent headache, blurred vision, confusion or seizures

• shortness of breath, chest pain, leg swelling or persistent abdominal pain

• unusual skin bruising and/or pinpoint round spots beyond the site of vaccination.

The most common time period for onset of TTS symptoms is 4–30 days after vaccination.

Early detection of TTS can prevent more serious complications developing. Guidance for health professionals is available which outlines when to suspect TTS, initial tests that can be performed in primary care and when to refer people for emergency care.

Death related to TTS

A 72-year-old woman from South Australia has sadly died after developing TTS following vaccination with her first dose of the AstraZeneca vaccine. The TGA extends its sincerest condolences to her family and loved ones. The woman was previously confirmed as having TTS related to vaccination. This was a very severe case of TTS involving blood clots in the brain and a very low platelet count. Her death was announced by the South Australian Deputy Chief Public Health Officer on Monday 12 July 2021.

TTS cases to date

Since last week’s report, a further seven reports of blood clots and low blood platelets have been assessed as confirmed or probable TTS likely to be linked to the AstraZeneca vaccine (Table 1). One of the cases reported this week is critically unwell in intensive care.

Table 1: Newly confirmed and probable TTS cases for the week of 9-15 July 2021‡ 

New confirmed TTS	New probable TTS
Four new cases: 67-year-old man from NSW 67 and 70-year old women from Victoria 71-year-old man from Western Australia	Three new cases: 48-year-old woman from Victoria 61-year-old woman from Western Australia 66-year-old woman from the ACT

‡As previously reported, the TGA determines whether a report is likely to represent TTS by assessing cases against a consistent set of criteria, based on the case definitions established by the UK’s Medicines and Healthcare products Regulatory Agency.

In addition to the new cases identified above, two cases previously reported as probable were reclassified to confirmed. This takes the total Australian reports assessed as TTS following the AstraZeneca vaccine to 51 confirmed cases and 32 probable cases, with a total of 83 cases overall from approximately 5.4 million doses of the AstraZeneca vaccine. 

Further information on one of the probable cases reported last week indicates it occurred after the second vaccine dose. The case appeared relatively mild and remains under investigation to determine whether or not it is linked to the vaccine. Based on UK data, the risk of TTS after the second dose is extremely low (1.7 cases per million second doses).

When assessed against the criteria used by the US Centers for Disease Control and Prevention (CDC), fewer than half of the cases reported to TGA are classified as Tier 1 cases which tend to have more serious outcomes. Tier 1 cases involve clots in an unusual location, such as the brain or abdomen (Table 2). The Tier 2 and unclassified TTS cases had only the more common clots like deep vein thrombosis or pulmonary embolism.

In Australia, severe cases of TTS appear to be more common in women, with nearly half of women with TTS receiving treatment in intensive care. In comparison, only 10% of men with TTS were treated in intensive care. Also, cases meeting the criteria for Tier 1 were twice as likely to occur in women compared to men. 

Table 2: Total confirmed and probable TTS cases to date by age and CDC classification

Age	Total cases	CDC classification†
				Tier 1	Tier 2	Not classified
<30 years	1	-	1	-
30-39	1	1	-	-
40-49	5	5	-	-
50-59	22	10	7	5
60-69	19	6	6	7
70-79	23	7	7	9
80+	12	3	4	5
All ages	83 (38 men, 45 women)	32	25	26

† The US CDC classification is defined as:

• Tier 1 = clots in an unusual location (such as the brain or abdomen) and a low platelet count with or without antibodies that activate platelets (anti-PF4 antibodies)

• Tier 2 = clots found in common locations (such as the leg or lungs) and a low platelet count and anti-PF4 antibodies

• Not classified = case does not meet the criteria for Tier 1 or Tier 2 (for example clots in common locations with low platelet count but no evidence of anti-PF4 antibodies).

Cases have most often occurred about two weeks after vaccination, although the time to onset (or diagnosis) has ranged from one to 54 days (Table 3) In some cases with a longer time to diagnosis, patients had experienced symptoms at an earlier stage but complicating factors, including symptoms from comorbidities, may have delayed a clear diagnosis. 

Table 3: Time to onset, treatment and outcomes for TTS cases*

Time to onset/ diagnosis (days)	Median (range)	12 (1-54)
Treated in ICU	At any point	24
	Currently	6
Outcome	Discharged	55
		In hospital	25
		Fatal	3

*Data is based on the most recent medical information available to the TGA

The Product Information now includes updated advice about the risk window for suspecting TTS. Specifically, people diagnosed with thrombocytopenia within 21 days of vaccination should be investigated for signs of a blood clot. Similarly, patients diagnosed with a blood clot within 21 days of vaccination should be tested for thrombocytopenia. 

In addition, the Product Information lists autoimmune disorders, including immune thrombocytopenia, as risk factors for TTS.

Immune thrombocytopenia (ITP)

The TGA is closely monitoring reports of ITP in light of a previously reported fatal case in a 61-year-old woman after receiving her first dose of the AstraZeneca vaccine. An external Vaccine Safety Investigation Group (VSIG) of clinical experts concluded that the woman’s death was likely linked to the vaccine.

ITP is a rare bleeding disorder that occurs when the immune system mistakenly destroys platelets, which help blood to clot. It can occur after the immune system is activated, for example by a viral infection or vaccination, and has been reported with other vaccines for hepatitis B, measles, mumps, rubella and influenza. In many cases the condition is mild with up to a third of people with ITP having no symptoms at all, or only minor bruising. However, about 5% develop severe bleeding. 

The risk of ITP associated with the AstraZeneca vaccine is still being investigated and characterised internationally. This follows an observation from a recent Scottish study which found that the first dose of the AstraZeneca COVID-19 vaccine was associated with a small increased risk of ITP of about 1 case per 100,000 people.

 

The TGA continues to evaluate reports of suspected ITP following vaccination and will report further information when it is known. To 11 July 2021, the TGA has received 31 reports of suspected ITP. These patients had an extremely low platelet count, signs of thrombocytopenia including unusual bruising, a nosebleed and/or blood blisters in the mouth. These symptoms occurred in a timeframe that suggested they could be linked to vaccination.

We encourage people to seek medical attention if they experience signs and symptoms that could suggest ITP, such as unusual skin bruising or clusters of small red or purple spots that do not lose their colour when pressed. Unusual bleeding is another sign, for example bleeding from the nose or mouth that is hard to stop, or blood in the urine or stools.

The Product Information has been updated to provide health professionals with further information about the risk of thrombocytopenia based on post-marketing experience.

Guillain-Barre Syndrome (GBS)

The TGA has been closely monitoring reports of GBS since the beginning of the COVID-19 vaccine rollout as it has been associated with other types immunisations such as influenza vaccines.

A review by the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (EMA PRAC) on 5-8 July 2021 was unable to confirm or rule out a possible association with the vaccine. However, the committee recommended that a warning about GBS be added to the Product Information to raise awareness amongst health professionals and consumers.

GBS is a rare immune disorder in which the body’s immune system attacks nerve cells. What causes it is not fully understood, but it often follows a viral infection or a bacterial type of gastroenteritis. GBS causes nerve inflammation and can result in pain, numbness, muscle weakness and difficulty walking. In many cases it resolves within months but can sometimes take up to two years.

To 11 July 2021, the TGA has received 52 reports of suspected GBS in people who have received the AstraZeneca vaccine. A possible link between GBS and the AstraZeneca vaccine remains under investigation by the TGA and involves looking more closely at whether these suspected cases meet the clinical criteria for GBS. This is a complex process requiring detailed patient information to exclude alternative causes and be certain of a diagnosis. The TGA is currently following up cases for this information and will report more on this issue as it becomes available.

We encourage people to seek medical attention if they experience symptoms that could suggest GBS. This includes weakness and paralysis in the hands or feet that can progress to the chest and face over a few days or weeks.

Capillary leak syndrome

Cases of capillary leak syndrome following immunisation with the AstraZeneca vaccine have been reported overseas. Two of these eight cases had a history of capillary leak syndrome. This is an extremely rare but severe relapsing-remitting condition where fluid from small blood vessels (capillaries) leaks into surrounding tissues. It is not well understood what triggers a relapse.

The TGA received one case of a patient who died from multi-organ failure but had signs of capillary leakage (reported previously). Although there was a temporal link with the vaccine, an expert Vaccine Safety Investigation Group was unable to establish a causal link as other causes could not be ruled out.

As a precautionary measure, the sponsor of the AstraZeneca vaccine has included a warning in the Product Information about capillary leak syndrome and specifically advise that the vaccine should not be used in people who have a history of this condition.

Up-to-date information about the expected side effects of the AstraZeneca COVID-19 vaccine can be found in the Consumer Medicine Information (for consumers) and Product Information (for health professionals).

Comirnaty (Pfizer) vaccine

Reports of side effects to the Comirnaty vaccine continue to be consistent with what has been observed in the clinical trials and by other medicine regulators overseas. To 11 July 2021, approximately 3.7 million doses of the Comirnaty vaccine have been administered.

Myocarditis and pericarditis

The TGA continues to monitor reports of myocarditis (inflammation of the heart) and pericarditis (inflammation of the membrane around the heart) following a safety concern in the US and Israel.

To 11 July 2021, the TGA has received 50 cases of suspected myocarditis and/or pericarditis. We are evaluating these cases in line with international regulatory criteria to confirm whether or not they are myocarditis and pericarditis.

At a recent meeting on 5-8 July, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that myocarditis and pericarditis can occur after vaccination but cases are very rare. This is consistent with previous advice from the US CDC’s Advisory Committee on Immunization Practices).

The TGA is currently working with Pfizer to add a warning statement to the Product Information and include myocarditis and pericarditis as an adverse event identified through post-marketing experience.

We know that myocarditis and pericarditis are much more common with COVID-19 infection and the risks to the heart can be more severe in this context. The benefits of protection against COVID-19 far outweigh these rare and generally mild side effects.

We encourage people to seek medical attention if they experience symptoms that could suggest myocarditis or pericarditis such as of chest pain, shortness of breath and palpitations. Typically, these have occurred within seven days of vaccination, and more commonly after the second dose of Comirnaty.

Up-to-date information about Pfizer Comirnaty can be found in the Consumer Medicine Information (for consumers) and Product Information (for health professionals).

Useful links

COVID vaccines – is it true?

Top 3 COVID-19 vaccine questions – COVID-19 testing with mild symptoms, quarantine and COVIDSafe behaviours – 13 July 2021

ATAGI statement on use of COVID-19 vaccines in an outbreak setting – published 13 July 2021

TGA COVID-19 vaccines hub

Australian Government Department of Health COVID-19 vaccines hub

AusVaxSafety (active surveillance activities and information)

COVID-19 vaccine symptom checker

Database of Adverse Event Notifications (DAEN)

Advice on COVID-19 vaccination during pregnancy – 9 June 2021

Comirnaty vaccine – phase III clinical trial

AstraZeneca vaccine – phase III clinical trial