COVID-19 vaccine weekly safety report - 06-05-2021

A number of factors influence reporting behaviour and reporting rates. Differences in reporting rates do not indicate any safety concerns specific to particular jurisdictions.

AEFI reporting statistics

The TGA has observed a marked increase in adverse event reporting since the beginning of the COVID-19 vaccine roll-out. Compared to the same period in 2020 (22 February to 2 May), there has been a nearly five-fold increase in the total number of reports received, due to a large number of AEFI reports for COVID-19 vaccines. This increase in reporting was expected due to the large number of COVID-19 vaccinations being carried out and promotion of adverse event reporting as part of the roll-out. As of 4 May 2021 over 2.3 million COVID-19 vaccinations had been performed in Australia.

This increase in reporting does not mean that COVID-19 vaccines are less safe than other vaccines. Reassuringly, nearly 80% of all reports are for common, short-lived and expected side effects such as headache, muscle and joint pain, fever and chills, fatigue/lethargy, injection site reactions, nausea and dizziness.

 

As part of a wider Department of Health communications program, the TGA has raised awareness of adverse event reporting channels and provided greater availability of services, including increasing the operating hours of the National Prescribing Service Adverse Medicine Events Line. There has been a 60-fold increase in the number of AEFI reports received directly from consumers compared to 2020. Nearly half of all consumer reports have been provided to the TGA via the NPS phone line. Reporting by health professionals, either directly to the TGA or via state and territory health departments, has also increased dramatically.

The TGA thanks the consumers and health professionals that have taken the time to report their experience to us. These reports play a critical role in our efforts to monitor the safety of COVID-19 vaccines. 

Reports of adverse events following immunisation are reviewed to assess the significance of the event and the likelihood that the vaccine contributed to it. Clinical staff (doctors, nurses and pharmacists) review serious events that may be caused by the vaccine. This review often includes gathering and considering relevant clinical information on the patient’s current and past medical history, risk factors and medications at the time of vaccination as well as any tests such as pathology and clinical notes, and where necessary involves discussion with the relevant state and territory health departments and the individual's health professionals. In some cases the TGA seeks expert advice on the likelihood of a link between a vaccine and an event.

The outcome of our assessment of individual reports is not routinely provided to the person who reported the adverse event. Our assessments are made for the purposes of identifying new safety information, rather than to guide clinical care. The health professionals treating the person who experienced the adverse event are best placed to advise them of the likely causes and management of their condition.

AEFI reports received in the week 26 April – 2 May 2021

Last week, the TGA received a total of 1967 AEFI reports for COVID-19 vaccines, including 1422 for the AstraZeneca COVID-19 vaccine, 524 for the Comirnaty vaccine, and 21 reports where the vaccine tradename was not reported. AEFI report numbers for the two vaccines are approximately proportional to the number of doses administered of each. The most common adverse events reported for COVID-19 vaccines during this period were:

• Headache

• Muscle pain

• Fever

• Fatigue

• Joint pain

Adverse events reported to the TGA may not be caused by the vaccine. Learn more about causality.

Not all adverse events are reported, especially for minor and well-known side effects. Learn more about reporting levels.

The information the TGA receives in reports reflects the view of the reporter. As the data entry and analysis of incoming reports is ongoing, the information may change as additional reports are completed, data quality is reviewed or further information is provided. Total numbers may also change as duplicate reports are identified.

Analysis of adverse event reports by product

Comirnaty BNT162b2 (mRNA) – Pfizer Australia Pty Ltd

Frequently reported adverse events

The most frequently reported adverse events for the Comirnaty vaccine up to 25 April 2021, from most to least common, were:

• Headache

• Muscle pain

• Fever

• Injection site pain

• Nausea

The occurrence of these adverse events is consistent with what is already known about the Comirnaty vaccine and with AusVaxSafety active surveillance data. Headache, muscle pain, nausea, fatigue and fever were commonly reported adverse events in clinical trials.

Adverse events of special interest

The TGA, like other vaccine safety monitoring programs around the world, closely monitors for specific adverse events known as ‘adverse events of special interest’. This close monitoring 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 rate of reporting of anaphylaxis for the Pfizer Comirnaty COVID-19 vaccine continues to decline over time. Of the 55 cases reported to 25 April, 16 cases meet the internationally accepted Brighton Collaboration case definition level 1 or 2, resulting in an estimated rate of 2.4 cases of confirmed anaphylaxis per 100,000 doses.

Blood clot disorders, such as stroke, pulmonary embolism and deep vein thrombosis, are also being monitored because of a possible link with COVID-19 disease itself. Analysis of reports received to 25 April 2021 shows the overall number of reports received for COVID-19 vaccines is no higher than the expected background rate for the more common type of blood clots in Australia. The TGA is continuing to calculate observed reporting rates of thrombosis following vaccination on a regular basis and compare these to the expected background rates. These reports for the Pfizer Comirnaty vaccine are not related to the very rare clotting disorder associated with very low platelets (thrombocytopenia) being investigated in relation to the AstraZeneca COVID-19 vaccine.

For all other adverse events of special interest, our review has not identified any confirmed safety signals.

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

COVID-19 Vaccine AstraZeneca (ChAdOx1-S) – AstraZeneca Pty Ltd

Frequently reported adverse events

The most frequently reported adverse events for the AstraZeneca COVID-19 vaccine up to 25 April 2021, from most to least common, were:

• Headache

• Fever

• Muscle pain

• Chills

• Fatigue

Adverse events of special interest

The TGA, like other vaccine safety monitoring programs around the world, closely monitors for specific adverse events known as ‘adverse events of special interest’. This close monitoring 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.

We received 163 reports of blood clot disorders (such as stroke, pulmonary embolism and deep vein thrombosis) for the AstraZeneca COVID-19 vaccine in Australia during the reporting period to 25 April 2021, including 44 reports in the week from 19-25 April. These reports were of blood clots in the veins (including venous thrombosis or venous thromboembolism) or arteries (including stroke). One hundred and seventeen of these were reports of venous thrombosis or venous thromboembolism. The overall number of reports received is no higher than the expected background rate for the more common type of blood clots in Australia, which occur in around 50 Australians every day irrespective of their vaccination status. The increase in cases of blood clots submitted to the TGA appears to be due to reporting of coincidental blood clots unrelated to vaccination, due to increased awareness of investigations into a rare and unusual clotting syndrome involving blood clots (thrombosis) with low blood platelet count (thrombocytopenia) following the AstraZeneca COVID-19 vaccine. 

Close monitoring of adverse events involving blood clots with low platelets

Very rare events of serious blood clots (thrombosis) with a low blood platelet count (thrombocytopenia) have been observed following vaccination with the AstraZeneca COVID-19 vaccine. There is growing evidence that these events, which are now referred to as thrombosis with thrombocytopenia syndrome (TTS), are caused by the vaccine. Further investigation is needed to identify the mechanism by which TTS may occur, further confirm how frequently it occurs and define possible risk factors. These investigations will help to confirm whether the vaccine causes TTS, and potentially identify ways to reduce the risk to people receiving the vaccine. For example, further investigation could provide information about people who may be at higher risk of TTS, or about how best to recognise and treat it early.

In response to this new safety concern, ATAGI has recommended that Comirnaty (Pfizer) be preferred over the AstraZeneca COVID-19 vaccine in people under the age of 50 years. Patient and provider information about this risk and an updated consent form have been produced. The TGA has worked with AstraZeneca to include information about this risk in the approved Product Information and Consumer Medicine Information.

The TGA continues to monitor for new information about TTS from around the world to inform ongoing consideration of the need for any further regulatory changes or advice to health professionals and consumers.

We are carefully reviewing any Australian reports of blood clots (thrombosis) and low blood platelet count (thrombocytopenia) following vaccination with the AstraZeneca COVID-19 vaccine to identify any further possible cases of this disorder. Since the last weekly COVID-19 vaccine safety report was published on 28 April, five reports of blood clots and low blood platelets have been assessed as TTS likely to be linked to the AstraZeneca COVID-19 vaccine. The cases were in a 74-year-old man and a 51-year-old woman from Victoria, a 66-year-old man from Queensland, a 64-year-old woman from Western Australia and a 70-year-old man from Tasmania. Symptom onset ranged from 7 to 32 days after vaccination.

These take the total Australian reports of probable TTS following the AstraZeneca COVID-19 vaccine to 11. To 2 May there had been approximately 1.4 million doses of the AstraZeneca vaccine administered. 

The TGA is actively investigating a further three possible cases of TTS. All three cases involved significant blood clots, but other test results, such as the anti-platelet factor 4 antibody ELISA, did not consistently indicate TTS and platelet counts were higher than the accepted threshold for TTS in some cases. The TGA is working with state and territory health departments to obtain further test results and information about medical history to inform further assessment.

As further cases are assessed, we will report on them in the weekly report. ATAGI continues to consider information about cases occurring in Australia and international data to inform recommendations for use of AstraZeneca COVID-19 vaccine.

Encouragingly, of the five cases reported in our statement on 23 April 2021 as hospitalised with thrombosis with thrombocytopenia following vaccination, four have now been discharged from hospital and are either at home or have returned to work.

In Europe and the United Kingdom, where many more doses of the AstraZeneca vaccine have been given, more than 200 cases involving thrombosis and thrombocytopenia have been reported to medicine regulators. The rate of reported cases in Australia is broadly consistent with the rate in Europe and the UK. There are international differences in the way cases are publicly reported, with TGA reporting on cases assessed as being highly consistent with thrombosis with thrombocytopenia syndrome likely to be caused by the vaccine, whereas other regulators may report on all cases involving thrombosis with thrombocytopenia, which may include cases with other causes.

Cases in Australia, as in Europe and the UK, were initially more commonly reported in younger people. With the AstraZeneca COVID-19 vaccine currently being used almost exclusively in people aged over 50 years, virtually all future cases of TTS in Australia will occur in this older age group. In the UK, thrombosis with thrombocytopenia has occurred in people aged from 18 years to 93 years. 

Health professionals should be alert to the signs and symptoms of thromboembolism and thrombocytopenia, as well as coagulopathies (bleeding disorders).

People who have been vaccinated should seek immediate medical attention if a few days after vaccination they develop:

• severe or persistent headache or blurred vision

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

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

Further information about the AstraZeneca COVID-19 vaccine can be found in the Consumer Medicine Information. (for consumers) and Product Information (for health professionals).

Active surveillance

AusVaxSafety is an active vaccine safety surveillance system that complements the TGA’s enhanced safety surveillance activities. Active vaccine safety surveillance uses SMS and a short survey to collect reports of AEFI directly from a subset of people receiving the vaccines. AusVaxSafety is an Australian Government-funded system that shares its findings with the TGA to assist our safety investigations and responses.

See details of AusVaxSafety’s latest COVID-19 vaccines safety data. 

The AusVaxSafety findings support the TGA’s assessment that the COVID-19 vaccines used in Australia meet safety standards

Useful links

TGA COVID-19 vaccines hub

Australian Government Department of Health COVID-19 vaccines hub

AusVaxSafety