Published: 29 September 2021

COVID-19

Adverse events following immunisation with COVID-19 vaccines: Safety Report #28 – 11 September 2021

Medsafe advises people NOT to make any decisions about vaccination based on information contained in this report. If you have questions or concerns about receiving a vaccine, please speak to a health care professional.

• Introduction
• Adverse events following immunisation (AEFI) reported
• Summary of reported deaths
• Observed versus expected analyses
• Adverse events of special interest
• Summary of safety signals
• Definitions
• More information

Introduction

This page provides information on the number of adverse events following immunisation (AEFI) reports received for COVID-19 vaccines.

An AEFI is an untoward medical event which follows immunisation and does not necessarily have a causal relationship with the administration of the vaccine. The adverse event may be an unfavourable or unintended sign, abnormal laboratory finding, symptom or disease.

The national roll-out of COVID-19 vaccines commenced on 20 February 2021. The vaccine currently available in New Zealand is Pfizer-BioNTech (Comirnaty). All medicines can cause side effects, the known side effects for Comirnaty are listed in the data sheet and consumer medicine information.

Suspected AEFI to COVID-19 vaccines are reported to the Centre for Adverse Reactions Monitoring (CARM). The Ministry of Health (through Medsafe) contracts the collection of this information to CARM, based at the University of Otago in Dunedin. Medsafe is closely monitoring the AEFI reported from the use of the COVID-19 vaccine. Find out more about vaccine safety monitoring.

Medsafe and CARM thank everyone who has contributed to the monitoring of COVID-19 vaccines. Please continue to report any adverse events following immunisation.

Adverse events following immunisation (AEFI) reported

The information below includes:

• AEFI reports received and vaccine doses administered
• AEFI reports by prioritised ethnicity and vaccine dose
• AEFI reports by age band and vaccine dose
• the top 10 most frequently reported AEFIs by vaccine dose.

AEFI reports received and vaccine doses administered, up to and including 11 September 2021

There were 2,352 non-serious and 63 serious reports this week. Sadly, six of these serious reports were notifications of deaths. Any possibility of a causal link is investigated as part of our routine investigations and no new safety concerns with the Comirnaty vaccine were raised by these reports.

Sadly, one of these 6 reports of death was for a 17-year-old consumer. The COVID-19 Vaccine Independent Safety Monitoring Board (CV-ISMB) have reviewed the death, which occurred after their first dose of the Pfizer/BioNTech vaccine. It was the opinion of the Board, with the current information available to it, that the cause of death, was unlikely related to the administration of the vaccine. The Board noted that expert haematology advice has been sought regarding other factors potentially involved and a report had been made to CARM regarding another ‘suspect medicine’ (ie, possible cause) which would be considered by the Medicines Adverse Reactions Committee (MARC) in due course.

For information about reported deaths, please refer to the summary of reported deaths section.

AEFI reports received by prioritised ethnicity and vaccine dose, up to and including 11 September 2021

Ethnicitya	Dose 1	Dose 2	Total
Māori	902	473	1,375
Pacific Peoples	387	287	674
Asian	1,471	801	2,272
European/Other	8,525	4,881	13,406
Unknownb	228	119	347
Total	11,513	6,561	18,074c

Notes:

1. The prioritised ethnicity classification system allocates each person to a single ethnic group, based on the ethnic groups they identify with. Where people identify with more than one group, they are assigned in this order of priority: Māori, Pacific Peoples, Asian, and European/Other. So, if a person identifies as being Māori and New Zealand European, the person is counted as Māori. See Ethnicity Data Protocols for further information.
2. There were 347 AEFI reports where the person’s ethnicity was not reported. Counts may change due to receipt of additional information. Ethnicity is not required for an AEFI report to be considered valid. See ‘Valid report’ in the Definitions section below.
3. The total is different from the cumulative total above because it excludes 3 AEFI reports received for infants who did not receive the vaccine.

AEFI reports received by age band and vaccine dose, up to and including 11 September 2021

Age	Dose 1	Dose 2	Total
10 - 19 years	1,094	122	1,216
20 - 29 years	1,896	924	2,820
30 - 39 years	2,180	1,182	3,362
40 - 49 years	1,941	1,232	3,173
50 - 59 years	1,909	1,293	3,202
60 - 69 years	1,384	980	2,364
70 - 79 years	751	566	1,317
80+ years	345	251	596
Unknowna	13	11	24
Total	11,513	6,561	18,074b

Note:

1. There were 24 AEFI reports where the person’s age was not reported. Counts may change due to receipt of additional information. Age is not required for an AEFI report to be considered valid. See ‘Valid report’ in the Definitions section below.
2. The total is different from the cumulative total above because it excludes 3 AEFI reports received for infants who did not receive the vaccine.

Top 10 most frequently reported AEFIs, any dose, up to and including 11 September 2021

Reaction	Number
Dizziness	5,549
Headache	5,546
Injection site pain	4,316
Lethargy	4,264
Nausea	3,899
Fever	2,437
Chest discomfort	2,082
Numbness	1,501
Syncope (fainting)	1,361
Musculoskeletal pain	1,326

Top 10 most frequently reported AEFIs, dose 1 only, up to and including 11 September 2021

Reaction	Number
Dizziness	3,902
Headache	2,788
Nausea	2,237
Injection site pain	2,192
Lethargy	2,061
Chest discomfort	1,270
Syncope (fainting)	1,014
Numbness	978
Fever	882
Shortness of breath	761

Top 10 most frequently reported AEFIs, dose 2 only, up to and including 11 September 2021

Reaction	Number
Headache	2,758
Lethargy	2,203
Injection site pain	2,124
Nausea	1,662
Dizziness	1,647
Fever	1,555
Chest discomfort	812
Musculoskeletal pain	794
Feeling of body temperature change	579
Influenza like illness	529

Please note that one adverse event report, which represents one person, may report on more than one symptom. Reports are sent to CARM if the reporter suspects that the vaccine may have caused the event. This does not necessarily mean that the vaccine did cause the event.

The number of reports can be influenced by how many people are being vaccinated, media attention, the nature of the events (eg, how painful the vaccination was), and other factors which vary over time. Not everyone who has an adverse reaction reports it, and some people may report AEFIs after each vaccination. The information here shows the number of reports not the number of people who experienced an AEFI.

The information is limited by the information provided in the report and may change over time due to quality control procedures and/or receipt of additional information. Non-valid reports are not included in the data.

Summary of reported deaths

Up to and including 11 September 2021, a total of 60 deaths were reported to CARM after the administration of the Comirnaty vaccine. Following medical assessments by CARM and Medsafe it has been determined that:

• 27 of these deaths are unlikely related to the COVID-19 vaccine
• 10 deaths could not be assessed due to insufficient information
• 22 cases are still under investigation.
• 1 death was likely due to vaccine induced myocarditis (awaiting Coroner’s determination)

By chance, some people will experience new illnesses or die from a pre-existing condition shortly after vaccination, especially if they are elderly. Therefore, part of our review process includes comparing natural death rates to observed death rates following vaccination, to determine if there are any specific trends or patterns that might indicate a vaccine safety concern. See below for more information about these observed-versus-expected analyses.

To date, the observed number of deaths reported after vaccination is actually less than the expected number of natural deaths.

Mortalities by age group up to and including 11 September 2021 reported to CARM

Age	Mortalities
10 - 29 years	1
30 - 59 years	8
60 - 79 years	27
80+ years	24

Observed-versus-expected analyses

It is important to note that no conclusions should be made from these observed-versus-expected analyses in isolation. Other investigations looking at pre-existing risk factors are always required.

The analyses below show that the number of deaths recorded in the mortality register for people vaccinated with the Comirnaty vaccine is lower than expected based on the average number of deaths in previous years over the same number of days (natural death rate).

For these observed-versus-expected analyses, we compare the vaccinated population to natural (expected) rates (taken from past data). The comparison is done by dividing the observed rate of death in the vaccinated population by the expected rate to give the relative risk (RR).

Observed / Expected Rate = Relative Risk (RR)

The methods used to calculate the relative risk also provide a confidence interval (CI). The confidence interval is a range of values that we are fairly sure our true value lies in. We are using a 95 percent confidence interval (95% CI), which is the range that will include the true value 95 percent of the time. If both the relative risk AND the lower end of the confidence interval are greater than one (>1.0), this is statistically significant and could indicate an increased risk of death in the vaccinated population. This will be highlighted in the table when applicable.

We are monitoring people for 21 days after vaccination. This monitoring period was chosen because people can receive their second dose a minimum of 21 days after the first dose. Additionally, of the deaths currently reported to CARM, the longest time period between vaccination and reported date of death was within 21 days. Age-specific natural (expected) death rates were obtained for the period 2008–2019.

These analyses do not consider causality and instead, report on all deaths that have occurred in the monitoring period (observed deaths). This results in a much higher number than those reported to CARM where the reporter (eg, family member or health care provider) might have had a suspicion the vaccine could have played a role. The number of observed deaths also includes deaths from other causes, such as deaths due to accidents, medical conditions, other medicines or medical treatments.

Please note that the mortality collections operate many weeks in arrears. This means that these observed-versus-expected analyses will only be updated once a month and will also be in arrears – for example, the tables below are for the period up to 30 June 2021.

Observed-versus-expected deaths^a by age group from any cause, up to 21 days after dose 1, 19 February 2021 to 30 June 2021

Age	Dose 1 – number administered	Expected deathsb in monitoring period	Observed deathsc in monitoring period	Relative riskc (95% confidence interval)
16 to 19	10,063	0.16	-	-
20 to 29	68,605	2.21	-	-
30 to 39	78,041	3.28	-	-
40 to 49	75,529	6.60	-	-
50 to 59	107,860	21.14	-	-
60 to 69	149,116	64.32	32	0.50 (0.34–0.70)
70 to 79	146,515	167.69	86	0.51 (0.41–0.63)
80+	84,403	412.08	359	0.87 (0.78–0.97)
Total	720,132	677.48	485	0.72 (0.65–0.78)

1. Expected and observed deaths among people who have received dose 1 of the Pfizer/BioNTech vaccine during the specified period, by age group. Inclusion criteria were: monitoring time of 21 days after receiving dose 1, all genders, all ethnicities, aged 16 years and older. The data was collected from the Mortality database.
2. Data for expected death rates was obtained from the AESI background rate (SAFE) study provided by the University of Auckland. The age-specific background rates used are the average from 2008-2019.
3. Some cells could not be calculated because the numbers were too low (<6).

Observed-versus-expected deaths^a by age group from any cause, up to 21 days after dose 2, 19 February 2021 to 30 June 2021

Age	Dose 2 – number administered	Expected deathsb in monitoring period	Observed deathsc in monitoring period	Relative riskc (95% confidence interval)
16 to 19	6,354	0.10	-	-
20 to 29	51,758	1.63	-	-
30 to 39	58,321	2.41	-	-
40 to 49	55,393	4.77	-	-
50 to 59	74,882	14.62	-	-
60 to 69	86,766	35.10	20	0.57 (0.35–0.88)
70 to 79	76,559	70.97	42	0.59 (0.43–0.80)
80+	45,523	179.56	197	1.10d (0.95–1.26)
Total	455,556	309.16	264	0.85 (0.75–0.96)

1. Expected and observed deaths among people who have received dose 2 of the Pfizer/BioNTech vaccine during the specified period, by age group. Inclusion criteria were: monitoring time of 21 days after receiving dose 2, all genders, all ethnicities, aged 16 years and older. The data was collected from the Mortality database.
2. Data for expected death rates was obtained from the AESI background rate (SAFE) study provided by the University of Auckland. The age-specific background rates used are the average from 2008-2019.
3. Some cells could not be calculated because the numbers were too low (<6).
4. The relative risk of 1.10 does not indicate there is an increased risk of mortality in this age group because the lower end of the confidence interval is 0.95 (ie, <1.0). The COVID-19 Independent Safety Monitoring Board (CV-ISMB) has reviewed AEFIs in the elderly and found that this group was not disproportionately affected by the vaccine. Medsafe will continue to monitor this closely.

For further reading about the methodology used to analyse death rates, see:

• Centers for Disease Control and Prevention (CDC) – Rapid Cycle Analysis (RCA) to monitor the safety of COVID-19 vaccines in near real-time within the Vaccine Safety Datalink. URL: https://www.cdc.gov/vaccinesafety/pdf/VSD-1342-COVID19-RCA-Protocol_FinalV1.1_508.pdf
• Kulldorff M, Davis RL, Kolczak M, et al. A maximised sequential probability ratio test for drug and vaccine safety surveillance. Sequential Analysis 30(1): 58–78. URL: https://www.tandfonline.com/doi/full/10.1080/07474946.2011.539924.

Adverse events of special interest

Adverse events of special interest (AESI) are pre-specified medically significant events that have the potential to be causally associated with the vaccine and must be carefully monitored. AESI can be serious or non-serious and can include:

• Events of interest due to their association with COVID-19 infection.
• Events of interest for vaccines in general (e.g. to the specific vaccine type or adjuvants).

The list of AESIs below takes into consideration the lists of AESIs from expert groups such as the Brighton Collaboration, manufacturers and other regulatory authorities. The AESI list changes based on the evolving safety profile of vaccines. It is important to note that although these adverse events may occur after being vaccinated with a COVID-19 vaccine in New Zealand, they are rare and may not necessarily be related to the vaccine. Medsafe and CARM review the reports to determine whether the vaccine may have played a role in the occurrence of these events.

Adverse events of special interest (AESI) up to and including 11 September 2021

AESI Category	AESI	Totala
Immune system disorders	Guillain-Barré Syndrome	6
	Thrombocytopenia	12
	Thrombosis with thrombocytopenia syndrome (TTS)	0
	Anaphylaxisb	47
Cardiovascular system	Myocardial infarction (heart attack)	20
	Myocarditis/pericarditis	85
Blood and lymphatic system	Thrombosis	15
	Embolism	35
	Deep vein thrombosis (DVT)	41
	Vasculitis	6
	Haemorrhage	64
Hepato-gastrointestinal and renal system	Acute kidney injury	9
	Acute liver injury	0
Nervous system	Aseptic meningitis	0
	Encephalitis	<6
	Stroke	39
	Bell's Palsy/facial paralysis	62
	Myelitis/myelitis transverse	<6
Infections and musculoskeletal	Erythema multiforme	<6
	Arthritis	17
	Herpes zoster	105
Pregnancy, puerperium and perinatal conditions	Abortion (spontaneous abortion /miscarriage)	<6

1. Includes all reports, both serious and non-serious. Counts below 6 are reported as <6 for privacy reasons. Counts may change due to receipt of additional information and subsequent reclassification of cases.
2. Includes reports meeting levels 1-3 of the Brighton Collaboration case definition.

Summary of safety signals

Summary of Medsafe’s investigations into possible safety signals

Safety signal	Outcome
Blood clots	Continue to monitor. See also the Monitoring communication
Appendicitis	Continue to monitor
Myocarditis/pericarditis	Information has been added to Comirnaty data sheet. See also the Alert communication
Herpes zoster	Continue to monitor
Bell’s palsy/facial paralysis	Continue to monitor
Menstrual disorder	Continue to monitor
Stroke	Continue to monitor
Tinnitus	Continue to monitor
AEFIs in the elderly	Continue to monitor and updated data sheet
Pancreatitis	Continue to monitor
Glomerular diseases	Continue to monitor
Guillain-Barré Syndrome	Continue to monitor
Thrombocytopenia	Continue to monitor
AEFIs in children	Continue to monitor

Definitions

Adverse event following immunisation (AEFI)

An AEFI is an untoward medical event which follows immunisation and does not necessarily have a causal relationship with the administration of the vaccine. The adverse event may be an unfavourable or unintended sign, abnormal laboratory finding, symptom or disease.

Serious adverse event following immunisation

An AEFI is considered serious if it:

• is a medically important event or reaction
• requires hospitalisation or prolongs an existing hospitalisation
• causes persistent or significant disability or incapacity
• is life threatening
• causes a congenital anomaly/birth defect
• results in death.

It is possible for different people to have experienced the same event but for the report to be serious for one person and non-serious for another person.

Adverse events of special interest (AESI)

An AESI is a pre-specified medically significant event that has the potential to be causally associated with the vaccine product based on past experience, the technology used to make the vaccine or the infection the vaccine is used to protect against. AESIs need to be carefully monitored and any potential association to vaccination confirmed by further analysis and studies.

Safety signal

Information on a new or known adverse event that may be caused by the vaccine and requires further investigation. Safety signals can be detected from a wide range of sources such as CARM reports, clinical studies and scientific literature.

Valid report

There are only four requirements for a valid AEFI report:

1. one patient identifier (eg, name, initials, gender, date of birth, age)
2. suspect medicine(s)
3. suspected reaction(s)
4. reporter details.

These four requirements are the minimum requirements. However, including more information in the report helps Medsafe to investigate the reaction more quickly. Reporting is easiest online.

More information

See the data sheets and consumer medicine information for the expected reactions for approved COVID-19 vaccines.

COVID-19 Vaccine Safety Monitoring Process

View Ministry of Health COVID-19 vaccine data

Latest listing of all cases received

The latest listing of AEFIs received is included in the attached spreadsheet. Medsafe advises patients NOT to make any decisions about vaccination based on information contained here.

Download AEFI-line-listing.xlsm