Published: 24 November 2021
Archived: 21 August 2024

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Adverse events following immunisation with COVID-19 vaccines: Safety Report #36 – 6 November 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.

• What you need to know
• 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

What you need to know – up to and including 30 October 2021

• The protective benefits of vaccination against COVID-19 far outweigh the potential risks of vaccination.
• The Ministry of Health, Medsafe, the Centre for Adverse Reactions Monitoring and manufacturers continue to closely monitor the safety of COVID-19 vaccines. We’ll respond to any safety issues right away and will inform New Zealanders about any risks that arise in New Zealand.
• For more information about Covid Vaccine Immunisation Programme, please go to Unite against COVID-19 or call Healthline 0800 611 116 to talk to someone about your concerns.
• There were 1,487 non-serious and 67 serious reports this week. Sadly, this week we have 6 more notifications of death. 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. For information about reported deaths, please refer to the summary of reported deaths.
• Up to 6 November 2021 a total of 7,045,721 doses of Comirnaty have been administered and 35,700 AEFIs were reported. This means that more than 7.0 million doses of Comirnaty were administered that did not result in a report of an adverse event. On average for every 10,000 people who are vaccinated 51 people report an AEFI. It is also important to keep in mind that a report can be submitted for any cause and is not necessarily associated with the vaccine.
• The next safety report (#37) will be published on 8 December 2021, for the period ending 20 November 2021.

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 by prioritised ethnicity and vaccine dose
• AEFI reports by age band and vaccine dose
• the top 10 most frequently reported AEFIs by vaccine dose
• reported AEFIs by reporter type.

AEFI reports received by prioritised ethnicity and vaccine dose, up to and including 30 October 2021

Ethnicitya	Dose 1	Dose 2	Total
Māori	1,735	1,153	2,888
Pacific Peoples	599	512	1,111
Asian	2,279	1,637	3,916
European/Other	15,700	11,455	27,155
Unknownb	401	222	623
Total	20,714	14,979	35,693c

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 623 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 7 AEFI reports received for infants who did not receive the vaccine.

AEFI reports received by age band and vaccine dose, up to and including 30 October 2021

Age	Dose 1	Dose 2	Total
10 - 19 years	2,292	1,034	3,326
20 - 29 years	4,129	2,529	6,658
30 - 39 years	4,420	3,157	7,577
40 - 49 years	3,474	2,882	6,356
50 - 59 years	3,056	2,560	5,616
60 - 69 years	1,928	1,596	3,524
70 - 79 years	958	834	1,792
80+ years	427	372	799
Unknowna	30	15	45
Total	20,714	14,979	35,693b

Note:

1. There were 45 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 7 AEFI reports received for infants who did not receive the vaccine.

Top 10 most frequently reported AEFIs, dose 1 and dose 2, up to and including 6 November 2021

Download a list of the top 50 most frequently reported AEFIs (any dose)..

Reported AEFIs by reporter type up to and including 6 November 2021

Reporter type	Number of reportsa
Public Patient	13,666
CIR Vaccinator	10,942
Nurse	6,111
Other	3,317
General Practitioner	2,932
Public: On behalf of a patient	1,179
Pharmacist	252
Not specified	112

1. The total number here differs from the total reported cases elsewhere because a single case can contain multiple reports from different sources.

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 6 November 2021, a total of 103 deaths were reported to CARM after the administration of the Comirnaty vaccine. Following medical assessments by CARM and Medsafe it has been determined that:

• 47 of these deaths are unlikely related to the COVID-19 vaccine
• 47 deaths could not be assessed due to insufficient information
• 8 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 6 November 2021 reported to CARM

Age	Mortalitiesa
10 - 29 years	3
30 - 59 years	18
60 - 79 years	48
80+ years	34

1. Counts may change due to receipt of additional information, for example, identification of duplicate reports.

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. Age-specific natural (expected) death rates were obtained for the period 2008–2019. One reason for the number of deaths in the vaccinated group appearing to be lower could be that healthcare professional of extremely frail patients give the advice not to get vaccinated.

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 31 August 2021.

Observed-versus-expected deaths^a by age group from any cause, up to 21 days after dose 1, 19 February 2021 to 31 August 2021

Age	Dose 1 – number administered	Expected deathsb in monitoring period	Observed deathsc in monitoring period	Relative riskc (95% confidence interval)
12 to 19	139,128	1.09	-	-
20 to 29	231,701	5.56	-	-
30 to 39	301,799	9.34	-	-
40 to 49	319,637	22.12	7	0.32 [0.13 – 0.65]
50 to 59	416,772	73.23	28	0.38 [0.25 – 0.55]
60 to 69	421,151	199.37	72	0.36 [0.28 – 0.45]
70 to 79	311,462	422.53	173	0.41 [0.35 – 0.48]
80+	162,158	920.16	505	0.55 [0.50 – 0.60]
Total	2,303,808	1,653.40	789	0.48 [0.44 – 0.51]

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 12 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. The observed deaths column (4th column) is a raw data observation, and this is used to calculate the relative risk (5th column). 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 31 August 2021

Age	Dose 2 – number administered	Expected deathsb in monitoring period	Observed deathsc in monitoring period	Relative riskc (95% confidence interval)
12 to 19	17,604	0.26	-	-
20 to 29	96,739	2.89	-	-
30 to 39	120,108	4.61	-	-
40 to 49	130,814	10.18	-	-
50 to 59	192,510	34.32	12	0.35 [0.18 – 0.61]
60 to 69	277,996	117.79	60	0.51 [0.39 – 0.66]
70 to 79	248,446	307.81	123	0.40 [0.33 – 0.48]
80+	132,721	695.84	458	0.66 [0.60 – 0.72]
Total	1,216,938	1,173.70	659	0.56 [0.52 – 0.61]

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 12 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. The observed deaths column is a raw data observation, and this is used to calculate the relative risk (5th column). Some cells could not be calculated because the numbers were too low (<6).

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 6 November 2021

AESI Category	AESI	Totala
Immune system disorders	Guillain-Barré Syndrome	15
	Thrombocytopenia	24
	Thrombosis with thrombocytopenia syndrome (TTS)	0
	Anaphylaxisb	87
Cardiovascular system	Myocardial infarction (heart attack)	39
	Myocarditis/pericarditis	235
Blood and lymphatic system	Thrombosis	39
	Embolism	82
	Deep vein thrombosis (DVT)	76
	Vasculitis	56
	Haemorrhage	95
Hepato-gastrointestinal and renal system	Acute kidney injury	14
	Acute liver injury	<6
	Pancreatitis	6
	Appendicitis	12
Nervous system	Aseptic meningitis	<6
	Encephalitis	<6
	Stroke	74
	Bell's Palsy/facial paralysis	128
	Myelitis/myelitis transverse	<6
Infections and musculoskeletal	Erythema multiforme	10
	Arthritis	42
	Herpes zoster	209
Pregnancy, puerperium and perinatal conditions	Abortion (spontaneous abortion /miscarriage)	25

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

New safety signal: Erythema multiforme

Medsafe investigated a possible safety signal of erythema multiforme (a skin immune reaction). The data was presented to the COVID-19 Independent Safety Monitoring Board (CV-ISMB) and there was consensus that there is no reason to suspect that the Comirnaty vaccine causes erythema multiforme. Medsafe will continue to monitor erythema multiforme through our usual safety monitoring processes.

COVID-19 vaccination in pregnancy: no safety concerns with Comirnaty

Medsafe and the COVID-19 Independent Safety Monitoring Board (CV-ISMB) has reviewed AEFI reports and the medical literature and considered that there is no evidence to suggest an increased risk of miscarriage after vaccination. The CV-ISMB emphasised the considerable risks to both mother and child of COVID-19 disease in pregnancy and considered that the available safety information supports routine vaccination of pregnant people with Comirnaty. See the monitoring communication.

Update on Menstrual disorders and unexpected vaginal bleeding

Medsafe conducted a full review of AEFI reports, as well as the international published literature and post-marketing safety reports provided by the sponsor (Pfizer). No evidence was found to suggest a link between vaccination with Comirnaty and menstrual disorders. This assessment was endorsed by the CV-ISMB. Medsafe will continue to monitor the rate and pattern of occurrence of this issue. See the monitoring communication.

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. Medsafe will continue to monitor this closely.
Herpes zoster	Continue to monitor
Bell’s palsy/facial paralysis	Continue to monitor
Menstrual disorder	Continue to monitor. See also the monitoring communication.
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
Erythema multiforme	Continue to monitor
Pregnancy	Continue to monitor. See also the monitoring communication.

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