COVID-19 vaccine weekly safety report - 28-04-2021

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 reports received in the week 19 April - 25 April 2021

Last week, the TGA received a total of 1942 AEFI reports for COVID-19 vaccines, including 518 for the Comirnaty vaccine, 1400 for the AstraZeneca COVID-19 vaccine, and 24 reports where the vaccine tradename was not reported. The most common adverse events reported for COVID-19 vaccines during this period were:

• Headache
• Muscle pain
• Fever
• Injection site reactions
• Lethargy

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 received up to and including 18 April 2021

Comirnaty BNT162b2 (mRNA) – Pfizer Australia Pty Ltd

Frequently reported adverse events

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

• Headache
• Muscle pain
• Fever
• Injection Site Reaction
• 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, injection site reaction 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.

Adverse events of special interest reported for the Comirnaty vaccine were:

• Anaphylaxis (52 reports)
• Bleeding disorder (27 reports)
• Seizure (13 reports)
• Facial weakness (11 reports)
• Loss of sense of taste or smell (9 reports)
• Cardiac event (5 reports)

We are continuing to carefully review the reports of possible anaphylaxis following Comirnaty to determine whether they are consistent with true anaphylaxis and whether they may have been caused by the vaccine.

The TGA’s assessment and advice provided by experts has determined that many cases reported as anaphylaxis do not meet the accepted case definition. These cases may have involved allergic reactions or immediate stress responses to vaccination that may appear similar to an anaphylactic reaction, with symptoms such as nausea, throat tightness or rapid heart rate. Although they might not meet the criteria for anaphylaxis, they still need to be monitored and taken seriously. There have been no reports of deaths associated with suspected anaphylaxis.

Of the 52 cases reported to 18 April, 14 cases meet the Brighton Collaboration case definition level 1 or 2, resulting in an estimated rate of 25 cases of anaphylaxis per million doses. The Brighton Collaboration is a group of international experts that has developed standardised guidelines for monitoring vaccine safety. The rate of anaphylaxis reporting for the Comirnaty COVID-19 vaccine to the TGA is trending downwards over time. We are continuing to monitor the rate.

Anaphylaxis remains very rare and guidance on the management of possible anaphylaxis remains as per the Product Information. Routine vaccination procedures include keeping people under observation for 15 minutes after vaccination and having appropriate medical treatment on hand so that anaphylaxis can be rapidly managed, if it occurs. A second dose of Comirnaty should not be given to those who have experienced anaphylaxis to the first dose.

Bleeding and blood clot disorders, such as stroke, pulmonary embolism and deep vein thrombosis, are being monitored because of a possible link with COVID-19 disease itself. These appear related to the more common type of blood clot conditions that can occur in around 50 Australians every day separate to vaccination. The overall number of reports received is no higher than the expected background rate for the more common type of blood clots in Australia. These 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.

Facial weakness has been reported rarely in clinical trials for Comirnaty. Seizures and cardiac events are being monitored because of a theoretical link with vaccines. These can also occur around the time of immunisation for reasons not related to the vaccine. The loss of sense of taste or smell are being monitored because of a theoretical link with COVID-19 disease. The loss of taste or smell may also be a non-specific symptom associated with feeling unwell. Our review does not suggest an increased risk of any of these adverse events of special interest above the background population rate with the Comirnaty vaccine.

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

Further information about 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, from most to least common, were:

• Headache
• Fever
• Muscle pain
• Chills
• Fatigue

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.

Adverse events of special interest reported for the AstraZeneca COVID-19 vaccine include:

• Bleeding disorder (97 reports)
• Anaphylaxis (59 reports)
• Seizure (27 reports)
• Cardiac Event (15 reports)
• Loss of sense of taste or smell (12 reports)
• Low platelets (12 reports)
• Facial weakness (10 reports)
• Liver injury (4 reports)
• Guillian-Barre Syndrome (1 report)

Anaphylaxis is a very rare side effect that may occur with any vaccine. Assessment of reports against the accepted case definition for anaphylaxis indicates a rate of less than 10 reports per million doses of the AstraZeneca COVID-19 vaccine, which is consistent with what is expected for vaccines in general in Australia and internationally. The rate of reported anaphylaxis is lower for the AstraZeneca COVID-19 vaccine than for Comirnaty because of the higher number of vaccine doses given.

Routine vaccination procedures include keeping people under observation for 15 minutes after vaccination and having appropriate medical treatment on hand so that anaphylaxis can be rapidly managed, if it occurs. A second dose should not be given to those who have experienced anaphylaxis to the first dose.

Seizures and facial weakness are being monitored because of a theoretical link with vaccines. They can also occur around the time of immunisation for reasons not related to the vaccine. The number of reports of seizures and facial weakness received in Australia is no higher than the expected background rate in Australia. We are continuing to monitor these events closely.

The loss of sense of taste or smell are being monitored because of a theoretical link with COVID-19 disease. Loss of taste or smell may also be a non-specific symptom associated with feeling unwell. Our review does not suggest an increased risk of this with the AstraZeneca COVID-19 vaccine.

For all other adverse events of special interest, our review does not suggest any confirmed safety signals at this time.

Close monitoring of adverse events involving blood clots with low platelets

We received 97 reports of bleeding and 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 18 April 2021, including 51 reports in the week from 12-18 April. Seventy-three of these were reports of venous thrombosis or venous thromboembolism (blood clots in the veins). The overall number of reports received is no higher than the expected background rate for the more common type of venous 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 thrombosis (blood clots) with thrombocytopenia (low blood platelet count) following the AstraZeneca COVID-19 vaccine.¹.

We are carefully reviewing any Australian reports of possible blood clots following vaccination with the AstraZeneca COVID-19 vaccine to identify any further possible cases of this disorder to better characterise this potential risk, which is now referred to as ‘thrombosis with thrombocytopenia syndrome’ (TTS). On 22 April the TGA convened an expert VSIG meeting to assess three further possible case of TTS in Australia. The VSIG concluded that the cases are likely to be linked to vaccination.

The total number of TTS cases reviewed by the VSIG and likely to be linked to vaccination is six (up to 22 April 2021). Based on this, the reported rate of TTS in Australia is approximately six per million doses (from 1,093,738 doses to 22 April 2021). The reported rate in the UK, where more than 21 million doses of the vaccine have been given, is approximately eight reports per million doses. Further cases of this syndrome may occur in Australia; we will continue to investigate and monitor the rate of occurrence, particular to verify that it remains consistent with international experience.

As noted in the approved Product Information, healthcare professionals should be alert to the signs and symptoms of thromboembolism and thrombocytopenia as well as coagulopathies. Vaccinated individuals should be instructed to seek immediate medical attention if they develop symptoms such as a severe or persistent headache, blurred vision, shortness of breath, chest pain, leg swelling, persistent abdominal pain or unusual skin bruising and/or petechia a few days after vaccination.

There have been 12 reports of low platelets up to 18 April 2021. Six of these have been associated with thrombosis and confirmed as TTS cases as previously discussed. The number of reports of low platelets overall is no higher than the expected background rate in Australia.

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.

Other TGA safety information

During the past week, the TGA has published the following COVID-19 safety-related information:

• AstraZeneca ChAdOx1-S COVID-19 vaccine: Three additional Australian cases of TTS likely linked to vaccine – 23 April 2021
  A Vaccine Safety Investigation Group (VSIG), a panel of expert advisors convened by the TGA, has concluded that three recently reported cases of thrombosis with thrombocytopenia are likely to be linked to vaccination. All three patients are clinically stable, have responded well to treatment and are recovering. Whilst meeting the international and UK criteria, two of the three cases appear to be milder forms of the syndrome that were recognised very early by the treating health professionals and are responding well to treatment. There are now six Australian reports of cases of thrombosis with thrombocytopenia following the AstraZeneca COVID-19 vaccine.  Five cases are in people aged less than 50 years, who were vaccinated prior to the decision by the Australian Technical Advisory Group on Immunisation (ATAGI) and the announcement by Government on 8 April 2021 that the Pfizer vaccine was preferred for patients under 50 years old. To 22 April there have been about 1.1 million doses of AstraZeneca COVID-19 vaccine administered in Australia.

Useful links

TGA COVID-19 vaccines hub

Australian Government Department of Health COVID-19 vaccines hub

AusVaxSafety

Footnote

1. Paragraph updated on 30 April 2021 to clarify the number and type of adverse events discussed.