COVID-19 vaccine weekly safety report - 12-08-2021

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 monitoring 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 with respect to possible side effects that may occur rarely. We conduct analyses to compare the number of reports of these events against the expected rate of events.

The TGA recently carried out a detailed investigation of reports of swollen lymph nodes (lymphadenopathy) following immunisation. As described below, nothing unexpected was found but we continue to monitor this side effect as part of our routine monitoring activities.

Enlarged lymph nodes (lymphadenopathy)

Swollen lymph nodes are a normal and known side effect of many vaccines. These events were observed in the clinical trials for the COVID-19 vaccines.

Swelling of one or more lymph nodes, also known as lymphadenopathy, usually occurs as result of a bacterial or viral infection but can also develop after immunisation because vaccines mimic an infection. Since the beginning of the vaccine rollout, the TGA has received more reports of enlarged lymph nodes after Comirnaty (Pfizer) than after the AstraZeneca vaccine – approximately 17 reports per 100,000 Comirnaty (Pfizer) doses versus 6 reports per 100,000 AstraZeneca doses. An investigation by our scientific and clinical staff at the TGA found that the majority of these reports were in younger people most likely reflecting the higher use of Comirnaty (Pfizer) in younger age groups.

Common areas where enlarged lymph nodes might be noticed are in the neck, armpits and groin. There have been claims in the media that increasing breast size is a possible short-term effect of the Pfizer vaccine. This is probably related to swollen lymph nodes under the arms which may give the impression of increased breast size. Changes in lymph nodes can also be a sign of other medical issues and there is concern that false readings on mammograms following vaccination could lead to additional unnecessary testing. After considering the risks of postponing breast screening, the Royal Australian and New Zealand College of Radiologists recommends that breast screening should not be delayed following COVID-19 vaccination, particularly for women at higher risk of breast cancer and those living in rural and remote regions, where access to screening may be limited.

A warning about lymphadenopathy is included in the Product Information for the Comirnaty (Pfizer) and AstraZeneca vaccines. Swollen lymph nodes usually develop within a few days of vaccination and resolve without treatment after a week or so. People should seek medical attention for enlarged lymph nodes that persist for more than a few weeks to rule out alternative causes.

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. Emerging data from the NSW outbreak indicates 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. Given the Delta strain seems to be more easily transmitted and possibly causes more severe disease, ATAGI reinforces the importance of reaching higher levels of first dose coverage as soon as possible.

Vaccination during pregnancy

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. This is due to the risk of complications from COVID disease for pregnant women and their unborn baby. To date, no serious pregnancy-related safety concerns have been identified with Comirnaty (Pfizer). More details are given on the RANZCOG website.

AstraZeneca COVID-19 vaccine

To 8 August 2021, approximately 7.4 million doses of the AstraZeneca vaccine have been administered in Australia. We continue to receive reports of suspected side effects to the vaccine. These are generally consistent with what is being observed internationally and 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 the AstraZeneca vaccine and is different from other clotting conditions. 

The latest rates of TTS in Australia were published in a statement from ATAGI on 28 July 2021.

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' includes information to help people make informed decisions about vaccination.

TTS cases to date

Since last week’s report, a further 11 reports of blood clots and low blood platelets have been assessed as confirmed or probable TTS likely to be linked to the AstraZeneca vaccine. All but one of the individuals were aged 60 years or over (Table 1).  

Table 1: Newly confirmed and probable TTS cases for the week of 6-12 August 2021‡

New confirmed TTS	New probable TTS
Two new cases: 22-year-old woman from Victoria 82-year-old man from Western Australia	Nine new cases: 61, 77, 84 and 85-year-old women from NSW Two 73-year-old men from NSW 60 and 78-year-old men from NSW 70-year-old man from Victoria

‡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.

This takes the total Australian reports assessed as TTS following the AstraZeneca vaccine to 104 cases (59 confirmed, 45 probable) from approximately 7.4 million vaccine doses. 

Five of the new probable TTS cases reported today may possibly be related to the second vaccine dose. These cases remain under investigation and will be considered by an external panel of experts in the coming week to determine whether they are related to vaccination or not. All of the cases were in older people who presented with relatively mild symptoms, including common clots in the lungs or leg that are not uncommon with advancing age.  All patients have been discharged from hospital. Expert review of similar cases found them unlikely to be TTS.

People who have already received their first AstraZeneca dose who have not experienced TTS should complete the two-dose schedule. To date, there are no TTS cases in Australia that have definitively been linked to a second dose of the AstraZeneca vaccine. Investigations overseas have shown that the risk of TTS after the second dose is extremely low (e.g.1.8 cases per million based data from the UK).

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). 

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 also twice as likely to occur in women compared to men.

No deaths have been reported in the last week. Six deaths have been reported over the preceding 4 months –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	CDC classification†
				Tier 1	Tier 2	Not classified
<30 years	2	1	1	-
30-39	2	2	-	-
40-49	6	6	-	-
50-59	23	11	7	5
60-69	24	9	6	9
70-79	33	9	8	16
80+	14	3	6	5
All ages	104 (48 men, 56 women)	41	28	35

† 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. These cases can be difficult to distinguish between normal clots and TTS and remain under investigation.

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	32
	Currently	6
Outcome	Discharged	86
	In hospital	12
	Fatal	6

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

Other safety signals with the AstraZeneca vaccine

Immune thrombocytopenia (ITP)

The TGA is investigating 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 8 August 2021, the TGA has received 46 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. These 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.

Guillain-Barre Syndrome (GBS)

The TGA has investigated reports of suspected GBS following vaccination with AstraZeneca vaccine. At this time, we are unable to establish a clear link between GBS and the AstraZeneca vaccine. International drug regulators have come to similar conclusions. As a precautionary measure, we have initiated discussions with the sponsor about potentially adding a warning to the Product Information.

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, and it 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 GBS resolves within months but can sometimes take up to 2 years.

To 8 August 2021, the TGA has received 79 reports mentioning GBS occurring after vaccination with the AstraZeneca vaccine. 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.

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

To 8 August 2021, approximately 6.3 million doses of the 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 and Product Information for Comirnaty (Pfizer).  To 8 August 2021, we have received 149 reports of suspected myocarditis and/or pericarditis following vaccination with 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 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.

We know that myocarditis and pericarditis are much more common with COVID-19 infection and damage to the heart is frequently severe after infection. The benefits of protection against COVID-19 far outweigh the risks from these rare and transient side effects.

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

Spikevax (elasomeran) vaccine

The COVID-19 vaccine sponsored by Moderna, elasomeran, will be marketed under the trade name Spikevax. It has recently been given provisional approval for use in Australia. Like Comirnaty (Pfizer), it is based on mRNA technology. It is given as 2 doses 4 weeks apart. Australia's initial doses of Moderna will be the existing vaccine widely rolled out in the US, UK, Europe and Singapore.

In Australia, the vaccine has been approved for use in people aged 18 years and over. Its use in children aged 12–17 years is currently being evaluated. No specific safety concerns have been identified to date and the decision of whether to extend use to this age group will be announced in the coming weeks. 

In a clinical trial of over 28, 000 people, the vaccine was very effective (94%) at protecting people against contracting COVID-19 compared to a placebo. The most commonly reported side effects in the trial included injection site reactions (pain, swelling and redness), headache, muscle and joint pain, chills, nausea and vomiting, swollen lymph nodes in the same arm as the injection, and fever. Side effects were more commonly reported after the second vaccine dose than after the first dose. 

As with Comirnaty (Pfizer) and the AstraZeneca vaccine, the TGA will be monitoring the safety of this new vaccine once it is rolled out.

Useful links

Top 3 COVID-19 vaccine questions – COVID boosters, COVIDSafe behaviours and Doherty Institute modelling – 10 August 2021

Top 3 COVID-19 vaccine questions – Pfizer for 12–15 years, TTS symptoms, Pfizer risks and PCR tests – 5 August 2021

Top 3 COVID-19 vaccine questions – Children and the delta variant, COVID-19 risk after vaccine, and opening borders – 5 August 2021

Australian Technical Advisory Group on Immunisation (ATAGI) weekly COVID-19 meeting – 4 August 2021

Latest COVID-19 weekly surveillance in NSW

Coronavirus (COVID-19) case numbers and statistics

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

COVID vaccines – is it true? 14 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