COVID-19 vaccine weekly safety report - 26-08-2021

Most commonly reported vaccine side effects

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

Monitoring of less common adverse events

The TGA, like other vaccine safety programs around the world, is continually monitoring for less common adverse events. This helps us to confirm the safety profile of COVID-19 vaccines, particularly for rare side effects.

Menstrual disorders and unexpected vaginal bleeding

The TGA recently carried out an investigation of menstrual problems (also known as period problems) and unexpected vaginal bleeding suspected to be related to COVID-19 vaccination. This was in response to increased reporting of these events in Australia and internationally. The investigation did not find evidence for a link between vaccination and menstrual problems, but we continue to monitor this issue as part of our routine vaccine surveillance activities.

The TGA’s investigation involved assessing rates of reporting within Australia and overseas, reviewing findings from other regulators and examining the medical literature. To 22 August 2021, we have received 322 reports detailing a menstrual disorder or unexpected vaginal bleeding following the Comirnaty (Pfizer) vaccine, 157 reports following the Vaxzevria (AstraZeneca) vaccine and 2 reports where the vaccine brand was not specified. The most commonly reported symptoms were heavy periods, irregular bleeding, bleeding between periods and painful periods. Vaginal bleeding in postmenopausal women has also been reported.

Evidence from this review does not support a link between vaccination and menstrual problems. The Medicines and Healthcare products Regulatory Agency in the UK - external site and the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee - external site came to similar conclusions following their own rigorous investigations.

Abnormal menstrual bleeding is very common regardless of vaccination and affects up to a quarter of women during their reproductive years. Many factors can cause period problems including stress, weight gain or loss and underlying conditions like polycystic ovary syndrome and uterine fibroids. Changes to the menstrual cycle have also been reported after infection with COVID-19 and in people with ‘long COVID’.

Women who experience changes to their periods that are unusual for them and persist over time should talk to their doctors. Any vaginal bleeding after menopause is considered abnormal and warrants medical attention.

Latest immunisation recommendations

COVID-19 outbreak

As the COVID-19 outbreak involving the Delta variant continues to grow, the risk of contracting COVID-19 disease remains significant. Data from the NSW outbreak - external site demonstrates that vaccination protects people from infection and even in the small number of vaccinated people who become infected it significantly reduces the severity of disease. In an outbreak, the Australian Technical Advisory Group on Immunisation (ATAGI) continues to encourage all people over the age of 18 years to strongly consider getting any available vaccine - external site, including the Vaxzevria (AstraZeneca) vaccine.

Vaccination during pregnancy and lactation

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and ATAGI recommend immunisation with the Comirnaty (Pfizer) vaccine at all stages of pregnancy - external site. This is due to the risk of complications from COVID-19 disease for pregnant women and their unborn baby. To date, no serious pregnancy-related safety concerns have been identified with Comirnaty (Pfizer).

Pregnant women who have already received a first dose of Vaxzevria (AstraZeneca) can get either it or the Comirnaty (Pfizer) vaccine for their second dose. The Pfizer vaccine is recommended for breastfeeding women who can continue breastfeeding before and after vaccination. More details are given on the RANZCOG website - external site.

Vaxzevria (AstraZeneca) vaccine

The Australian brand name for this vaccine has been changed from ChAdOx1-S to Vaxzevria to be consistent with its name overseas. To 22 August 2021, approximately 8.8 million doses of the vaccine have been administered in Australia. The reports of suspected side effects we receive for this vaccine are consistent with what is being observed internationally. Most are expected side effects that resolve within a few days.

Thrombosis with thrombocytopenia syndrome (TTS)

TTS is a rare event involving serious blood clots with a low blood platelet count. It is triggered by the immune system’s response to Vaxzevria (AstraZeneca) and is different from other clotting conditions.

Rates of TTS in Australia were published in a statement from ATAGI on 18 August 2021 - external site.

While TTS is very rare, some people may have concerns that they can discuss with their doctor. 'Weighing up the potential benefits against risk of harm from COVID-19 Vaccine AstraZeneca - external site' includes information to help people make informed decisions about vaccination.

Outcomes of 24 August 2021 Vaccine Safety Investigation Group (VSIG) meeting

The TGA convened an expert external group to review the clinical details of 5 people reported to have suspected TTS following a second dose of the Vaxzevria (AstraZeneca) vaccine. The group included experts in infectious diseases, vaccinology, haematology, respiratory medicine, immunology and public health together with a consumer representative and an expert in communication. 

All of the cases considered by the panel were in older people who presented with relatively mild symptoms. Based on the information supplied to the TGA, 2 cases were assessed as not being related to vaccination. For the other 3 cases, medical evidence did not support a causal link with the vaccine. All 3 individuals had clots in common sites (such as the legs and lungs) and 2 of the 3 people had existing medical conditions that may have caused clotting even without the vaccine. For all 3 patients, tests for antibodies that activate platelets (PF4 antibodies) found either no antibodies or extremely low levels. However, further testing to clarify this is underway and an update will be provided once test results are available. The panel commended the treating clinicians for appropriately investigating and managing these patients, all of whom have been discharged from hospital. 

The panel noted that, to date, none of the suspected cases of TTS following a second dose have been definitively linked to Vaxzevria (AstraZeneca) in Australia. Investigations overseas have shown that the risk of TTS after the second dose is extremely low (for example, 1.8 cases per million based on data from the UK - external site). People who have already received their first AstraZeneca dose who have not experienced TTS should complete the two-dose schedule.

TTS cases to date

Since last week’s report, a further 8 reports of blood clots and low blood platelets have been assessed as confirmed or probable TTS likely to be linked to the first dose of Vaxzevria (AstraZeneca). Six of the 8 individuals were aged over 60 years (Table 1).

Table 1: Newly confirmed and probable TTS cases for the week of 20-26 August 2021‡

New confirmed TTS	New probable TTS
Two new cases: 34-year-old woman from NSW 68-year-old woman from South Australia	Six new cases*: 27 and 69-year-old women from Victoria 73, 74 and 75-year-old women from NSW 83-year-old man from NSW

‡As previously reported, the TGA determines whether a report is likely to represent TTS by assessing cases against accepted criteria established by the UK’s Medicines and Healthcare products Regulatory Agency.
*In last weeks’ report, we stated the incorrect age for a patient from NSW with probable TTS – the man was aged 75 years-old, not 76 years as reported. 

In addition to the new cases reported today, 4 cases previously reported as probable TTS have been reclassified as confirmed TTS. Following review of additional medical information, 4 previous cases have been reclassified as unlikely to be TTS – 2 of the cases were considered unlikely based on VSIG advice, and review of the other 2 cases identified more likely causes of their thrombosis and thrombocytopenia. This takes the total Australian reports assessed as TTS following the Vaxzevria (AstraZeneca) vaccine to 116 cases (67 confirmed, 49 probable) from approximately 8.8 million vaccine doses. 

When assessed against the criteria used by the US Centers for Disease Control and Prevention - external site (CDC), fewer than half of the cases reported to the 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).

In Australia, severe cases of TTS appear to be more common in women in younger age groups. Nearly half of the TTS cases in women required treatment in intensive care. Cases meeting the criteria for Tier 1 were 2.5-times more likely to occur in women compared to men.

To date, 6 deaths have been assessed as related to TTS – 5 of the 6 deaths occurred in women aged 34, 48 (2 cases), 52 and 72-years-old. The other death was in a 44-year-old man.

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

Age	Total cases	Reports per  100,000 doses‡	CDC classification†
						Tier 1	Tier 2	Not classified
<30 years	4	2.5  (<50 years)	1	1	2
30-39	3		3	-	-
40-49	6		6	-	-
50-59	26	2.7	13	8	4
60-69	28	1.6	10	8	10
70-79	33	2.1	9	10	14
80+	16	1.6	4	6	6
All ages	116 (50 men, 66 women)	2.0	46	34	36

‡ Rates of TTS are calculated based on first doses of the Vaxzevria (AstraZeneca) vaccine as of 12 August to account for the time to onset of TTS. These rates are estimates of risk based on small numbers of cases so far.  

† 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 2 weeks after vaccination, although the time to onset (or diagnosis) has ranged from one to 83 days (Table 3). To date, cases presenting with a longer time to onset (over 50 days) have been designated as probable cases and have presented with common forms of clots. It can be difficult to distinguish between normal clots and TTS for these cases and they remain under investigation. As more is learnt about TTS internationally, we are considering modifying our case criteria, such as including the time to onset of symptoms as part of the criteria for confirming TTS. If the criteria are updated, it may result in some cases being reclassified as unlikely to be TTS because they present such a long time after vaccination and/or are likely to be due to other causes.

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

Time to onset/ diagnosis (days)	Median (range)	12 (1-83)
Treated in ICU	At any point	33
	Currently	3
Outcome	Discharged	96
	In hospital	14
	Fatal	6

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

Other safety signals with the Vaxzevria (AstraZeneca)

Guillain-Barre Syndrome (GBS)

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). As a precautionary measure, a warning statement about GBS has been added to the Product Information. This is in response to rare cases following vaccination in Australia and internationally.

The warning statement reads “Very rare events of demyelinating disorders, such as Guillain-Barré Syndrome (GBS), have been reported following vaccination with Vaxzevria. A causal relationship has not been established. Healthcare professionals should be alert of signs and symptoms of demyelinating disorders to ensure correct diagnosis, in order to initiate adequate supportive care and treatment, and to rule out other causes.”

GBS is a rare immune disorder in which the body’s immune system attacks nerve cells. The causes are not fully understood, but it often follows a viral infection (such as influenza, cytomegalovirus and glandular fever) or gastroenteritis caused by a bacteria called Campylobacter jejuni. GBS has been associated with other types of immunisations, such as influenza vaccines - external site and has been reported with COVID-19 infection. GBS causes nerve inflammation and can result in pain, numbness, muscle weakness and difficulty walking. It tends to affect both sides of the body. In many cases symptoms resolves within months but can sometimes take up to 2 years.

To 22 August 2021, the TGA has received 89 reports mentioning GBS occurring after vaccination with Vaxzevria (AstraZeneca). These cases will be considered as part of our ongoing monitoring of this signal.

We encourage people to seek medical attention if they experience symptoms that could suggest GBS as early medical care can reduce severity and improve outcomes. Symptoms to look out for include weakness and paralysis in the hands or feet that can progress to the chest and face over a few days or weeks.

Anxiety-related reactions

A warning about anxiety-related reactions following vaccination has been added to the Product Information for Vaxzevria (AstraZeneca). Reactions such as fainting or feeling faint, hyperventilation or stress-related events may occur in response to the needle injection or with the process of vaccination itself.

Stress-related reactions are not unique to COVID-19 vaccination and can occur with any procedure involving a needle. It is important that precautions are in place to avoid injury from fainting.

Immune thrombocytopenia (ITP)

The TGA continues to monitor and investigate reports of suspected ITP, a type of thrombocytopenia or low platelet count. We will communicate the outcomes of this investigation, including any regulatory actions, when it is complete. To 22 August 2021, the TGA has received 56 reports of suspected ITP following vaccination. These patients had an extremely low platelet count, and signs of thrombocytopenia which may include unusual bruising, a nosebleed and/or blood blisters in the mouth. Their symptoms occurred in a timeframe that suggested they could be linked to vaccination and no other obvious cause was identified based on the information provided to TGA. However, apart from one fatal case that was assessed by an expert Vaccine Safety Investigation Group as being likely to be vaccine related, these cases have not been definitively linked to vaccination.

ITP can occur when the immune system is activated, for example by a viral infection or vaccination, and mistakenly destroys platelets which help blood to clot. In many cases it is mild with up to a third of people having no symptoms at all, or only minor bruising. However, about 5% develop severe bleeding. 

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.

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

Comirnaty (Pfizer) vaccine

To 22 August 2021, approximately 8.2 million doses of Comirnaty (Pfizer) have been administered in Australia. Reports of suspected side effects of the Comirnaty (Pfizer) vaccine received by the TGA are consistent with what has been observed in the clinical trials and by other medicine regulators overseas.

Myocarditis and pericarditis

Following investigations by the TGA and international drug regulators, a warning statement about myocarditis (inflammation of the heart) and pericarditis (inflammation of the membrane around the heart) has been included in the Consumer Medicine Information - external site and Product Information - external site for Comirnaty (Pfizer). 

These rare effects on the heart typically occur within 10 days of vaccination, particularly after the second dose of Comirnaty (Pfizer) and more often in younger men. While cases are usually transient and resolve following rest, some patients require treatment in hospital. 

We know that myocarditis and pericarditis are much more common with COVID-19 infection and damage to the heart is frequently severe after infection. ATAGI, in collaboration with Cardiac Society of Australia and New Zealand (CSANZ), have emphasised that the protective benefits of the Comirnaty (Pfizer) vaccine greatly outweigh the risk of these rare side effects - external site. The vaccine continues to be recommended for individuals aged 16 years and above and for those aged 12–15 who have an increased risk of severe illness from COVID-19 or who identify as Aboriginal or Torres Strait Islander.

To 22 August 2021, we have received 235 reports of suspected myocarditis and/or pericarditis following vaccination with Comirnaty (Pfizer). These reports reflect the observations of the people reporting them and have not been confirmed as having been caused by the vaccine. Some events may be coincidental and would have happened anyway, regardless of vaccination.

We encourage people to seek medical attention if they experience symptoms that could suggest myocarditis or pericarditis including chest pain, palpitations (irregular heartbeat) fainting or shortness of breath after receiving the vaccine, particularly if they occur within 1–5 days. Initial tests for those presenting with symptoms include ECG, troponin and chest X-ray.

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

AusVaxSafety reaches a new milestone

Since the beginning of the national roll-out of COVID-19 vaccines in February 2021, over 2 million surveys have been completed by Australians who have received a vaccine as part of AusVaxSafety’s active COVID-19 vaccine surveillance program. The surveys, which are sent via SMS or email, are designed by vaccine experts and give participants the opportunity to report any adverse events they may have after receiving the COVID-19 vaccine. The data collected is released to the public each month - external site and complements the TGA’s enhanced vaccine surveillance activities.

To participate, ask the recovery nurse for the survey in the waiting room after you have received your COVID-19 vaccination. For more information on the AusVaxSafety program visit www.ausvaxsafety.org.au - external site.

Useful links

Australian Technical Advisory Group on Immunisation (ATAGI) weekly COVID-19 meeting update – 18 August 2021 - external site

Top 3 COVID-19 vaccination questions – Vaxzevria, vaccinating when pregnant and why you should vaccinate – 24 August 2021 - external site

Top 3 COVID-19 vaccine questions – Recovery from COVID-19, Health professional questions and side effects post COVID-19 vaccine – 20 August 2021 - external site

Latest advice on COVID-19 vaccination for pregnant and breastfeeding women – 6 August 2021 - external site

Latest COVID-19 weekly surveillance in NSW - external site

Coronavirus (COVID-19) case numbers and statistics - external site

COVID-19 vaccines: Frequently asked questions – 15 July 2021 - external site

COVID vaccines – is it true? 14 July 2021 - external site

TGA COVID-19 vaccines hub

Australian Government Department of Health COVID-19 vaccines - external site hub

AusVaxSafety (active surveillance activities and information) - external site

COVID-19 vaccine symptom checker - external site

Database of Adverse Event Notifications (DAEN) - external site

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

Comirnaty (Pfizer) vaccine – phase III clinical trial - external site

AstraZeneca vaccine – phase III clinical trial - external site