COVID-19 vaccine weekly safety report - 21-04-2021

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 12 April - 18 April 2021

Last week, the TGA received a total of 2841 AEFI reports for COVID-19 vaccines, including 657 for the Comirnaty vaccine, 2157 for the AstraZeneca COVID-19 vaccine, and 29 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
• 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 received up to and including 11 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
• Nausea
• Fever
• Fatigue

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.

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

• Anaphylaxis (45 reports)
• Bleeding disorder (15 reports)
• Facial weakness (10 reports)
• Seizure (10 reports)
• Loss of sense of taste or smell (7 reports)
• Cardiac event (3 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 45 cases reported to 11 April, 16 cases meet the Brighton Collaboration case definition level 1, 2 or 3, resulting in an estimated rate of 35 cases of anaphylaxis per million doses. The Brighton Collaboration is a group of international experts that has developed standardised guidelines for monitoring vaccine safety. Although anaphylaxis remains very rare, this may be an overestimate of the rate of true anaphylaxis, resulting from including cases in Brighton Collaboration case definition levels 2 and 3, which are less certain cases of anaphylaxis, or it may reflect the increased reporting of adverse events by health professionals and consumers resulting from the intense interest in COVID-19 vaccines. Following advice from the Advisory Committee on Vaccines, the TGA is undertaking further assessment to identify cases that meet Brighton Collaboration case definition levels 1 and 2 and calculate the resulting rate of anaphylaxis.

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 occurrence of these adverse events is consistent with what is already known about the vaccine and with AusVaxSafety active surveillance data. They were commonly reported 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 AstraZeneca COVID-19 vaccine include:

• Anaphylaxis (48 reports)
• Bleeding disorder (47 reports)
• Seizure (19 reports)
• Loss of sense of taste or smell (10 reports)
• Low platelets (5 reports)
• Facial weakness (4 reports)
• Liver injury (3 reports)

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. We will continue to monitor these reports.

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 47 reports of possible bleeding disorders including blood clots for the AstraZeneca COVID-19 vaccine in Australia during the reporting period to 11 April 2021, including 37 reports in the week from 4-11 April. These reports were of blood clots in the veins or arteries (including 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 thrombosis (blood clots) with thrombocytopenia (low blood platelet count) following the AstraZeneca COVID-19 vaccine.

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 16 April the TGA convened an expert VSIG meeting to assess a third possible case of TTS in Australia. The VSIG concluded the case is likely to be linked to vaccination.

The total number of TTS cases reviewed by the VSIG and likely to be linked to vaccination is three (up to 16 April 2021). Based on this, the reported rate of TTS in Australia is approximately three per million doses (from 926,424 doses to 16 April 2021). The reported rate in the UK, where more than 20 million doses of the vaccine have been given, is approximately five reports per million doses.

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 five reports of low platelets up to 11 April 2021. Two 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

AusVaxSafetyis 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 vaccine safety-related information:

• AstraZeneca ChAdOx1-S COVID-19 vaccine: Third case of thrombosis with thrombocytopenia –16 April 2021
  A Vaccine Safety Investigation Group (VSIG), a panel of expert advisors convened by the TGA, has concluded that a recently reported case of thrombosis with thrombocytopenia is likely to be linked to vaccination. This is the third Australian report of a case of thrombosis with thrombocytopenia following the AstraZeneca COVID-19 vaccine. The case occurred in a woman in her 40s who was vaccinated in NSW. Sadly, this person died in hospital and we extend our sincerest condolences to her family.

Useful links

TGA COVID-19 vaccines hub

Australian Government Department of Health COVID-19 vaccines hub

AusVaxSafety