- There are different ways one can report adverse events after Covid-19 vaccination.
- When this happens, there is a process of assessing the link between the reported adverse event and the vaccination.
- Currently, Sahpra has received 86 death reports after Covid vaccination; 46 are under investigation and 40 have been assessed.
Tracking any potential side effects of a treatment or vaccine is crucial once it is rolled out to the broader population. While Covid-19 vaccines have undergone intensive safety monitoring in clinical trials, these studies can only tell us so much.
Real-world data can, for example, tell us how well the vaccines work in parts of the population not included in the trials, such as the elderly or those with comorbidities. And reporting any suspected adverse events (medical problems) after vaccination forms part of this safety monitoring process.
In South Africa, there are four ways to report adverse events after receiving a Covid-19 vaccine:
- The Med Safety app, downloaded from App Stores for Android and iOS phones
- Reporting to a health facility, such as a clinic or pharmacy, where they will complete the report on your behalf
- Calling the Covid-19 hotline on 0800 029 999
The Med Safety app was launched in April 2021 by the South African Health Products Regulatory Authority (Sahpra), and it can be used by healthcare professionals and the public. It was designed to simplify and encourage people to report adverse events following vaccination.
Speaking at a media briefing on 13 September, Mafora Matlala, Sahpra’s pharmacovigilance manager, said that watching the performance of medicines and vaccines on the market, and understanding the mechanisms involved, will help health experts and officials prevent these problems in future.
The Med Safety app, she said, helps to strengthen data quality and replaces the need for paper forms. As of August 2021, the app had 4 470 new users and 6 183 active users.
What happens after reporting these events?
Also on the panel was Professor Hannelie Meyer, chairperson of the National Immunisation Safety Expert Committee (Nisec). Sahpra is working with NISEC, an independent ministerial advisory committee.
Meyer discussed the process of assessing the link between an adverse event and vaccination. “It is human nature to put it, or blame things, on a single, major cause,” she said. “And we often make the mistake of blaming something that occurred earlier … where we assume that one event must be the cause of a related event, simply because it occurred earlier.”
It’s important to understand that an adverse event following vaccination does not equal an adverse event caused by vaccination, she said.
The golden rule is to report anything of concern, as this will result in a paper-based or electronic-case reporting form, said Meyer. With adverse events, these are generally mild or minor events. “These are the ones we expect to see based on the clinical trials, and they subside within two to three days,” she said.
But then there are the severe, serious events, which are less frequent:
- The need for in-patient hospitalisation
- The event is life-threatening
- Persistent or significant disability
- Birth defects
- A medically important event or reaction after vaccination
How the investigations are done
The investigation is then carried out by the district surveillance teams within the provinces, who are part of the National Department of Health.
“They do in-detail investigations of each and every one of these cases. They collect a lot of information and while doing so, complete a case investigation form. All of these things on this list, they collect in the form of evidence, such as lab results, clinical reports from the medical practitioner, which vaccine was administered, an interview with the person who administered the vaccine; an interview with the vaccine recipient, etc.,” said Meyer.
Once all of this information is available, it is sent to NISEC, who then becomes responsible for doing the causality assessment.
“With the causality assessment, a scientific process is followed, and we are using well-recognised methodology by the World Health Organization,” said Meyer.
Ensuring it’s an eligible case
Before NISEC can start with an investigation, they need to ensure that it’s an eligible case. That means they will need to have essential evidence, including the person’s personal details; the vaccine given (e.g. Pfizer or J&J); the adverse event experienced; dates of events; clinical notes; laboratory results; co-existing conditions of the person; other medicines taken by the individual; previous allergies of the individual; and an autopsy report.
Without the above, it wouldn’t be possible to determine if there’s a likelihood of a causal association between the event and the vaccine. The case, then, would turn out to be ineligible for a causality assessment.
Meyer explained some of the factors that are considered.
Ruling out another cause
During their assessment, NISEC will look at whether there is strong evidence to confirm another cause for the reported event. Part of this would be to look at the medical history from the patient’s records. There will be a clinical examination by medical professionals, as well as any investigations, such as a lab or autopsy report.
Could it be a vaccination error?
Meyer explained that the team assessing the case would determine whether there might have been a vaccination error. For example, the vaccine could have been used beyond its expiry date; it could have been administered in an unsterile manner; there could have been an error in the vaccine handling process (such as cold chain or storage); or it could have been administered incorrectly (such as the wrong dose).
Or the vaccine product itself?
NISEC also considers whether the vaccine product itself caused an adverse event. This information can be obtained from the literature or clinical trials that may indicate whether the event is common, such as swelling at the injection site.
Timing is key
“They look at whether the event happened within a specific time window. All adverse events or most of them have a specific time window,” said Meyer, citing anaphylaxis, a potentially life-threatening allergic reaction, as an example. This has been seen in an extremely small number of people who received the mRNA vaccines by Pfizer or Moderna.
The condition, however, usually happens within 15 minutes after vaccination and can be treated immediately with epinephrine.
Other questions that would form part of their investigation include:
- Has it occurred in the past after administration of a similar vaccine?
- Did this occur independently of vaccination?
- Could this event have occurred in this patient without vaccination?
- Are there any pre-existing conditions or risk factors that could have contributed to the event?
- Is this person taking any medication that could have resulted in this event?
Looking at the background rate
In this process, it’s important to look at the normal background rate of a certain event that has been reported, and then to compare it to the rate at which it is happening after vaccination, said Meyer.
“You look at the data and see if there are any unusual patterns in this particular event among the vaccinated people compared to the unvaccinated people,” she said.
Professor Linda-Gail Bekker, co-investigator of the Sisonke trial in SA, previously told Health24: “If we see a signal outside of what is the expected rate for that population, then there would be a reason to say, ‘Hold on, we think we've got something here.'"
Cases of a neurological disorder called Guillain-Barré syndrome (GBS), for example, have been reported following vaccination with the Johnson & Johnson (J&J) vaccine. In the Sisonke trial, there was one reported case of the disorder among nearly 500 000 vaccinated healthcare workers.
In the US, there have been only around 100 cases reported out of close to 13 million people receiving the vaccine, as of July 2021. On the other hand, an estimated 3 000 to 6 000 people develop GBS in the US each year. Therefore, given that the observed rate of GBS in people getting vaccinated against Covid-19 is lower than the usual rate of GBS, it is enough to categorise the occurrences as rare.
Once the entire process is completed, the investigators are able to classify the event, said Meyer.
Coincidental to vaccination
Meyer said that it’s common for adverse events to take place coincidentally with the vaccination. Some cases would, therefore, be classified as “coincidental to vaccination”.
“The reason for that is that people have comorbidities. We are vaccinating large populations of people, and many of them are in the older age groups with comorbidities,” she said.
Serious AEFIs statistics
From 17 May 2021 to 31 August 2021, more than 12 million vaccines had been given in SA. For this period, Sahpra and NISEC received 86 reports of death (0.0007%) among vaccine recipients.
A total of 46 cases are currently under investigation and 40 have been investigated and causality assessed.
Outcome of causality assessment
Meyer said that 34 cases were found to be coincidental to vaccination. In other words, the deaths would have happened regardless of whether the person was vaccinated or not.
“Covid vaccines [can] prevent people dying from Covid if they’re vaccinated in time. But the vaccines cannot prevent [death] from chronic diseases,” stressed Meyer.
Thirteen of those people had Covid disease (they either had Covid at the time of vaccination or developed it shortly after vaccination). One case was a breakthrough infection. Importantly, while vaccines offer strong protection, it can take two to three weeks for the protection to build and be effective against severe Covid and death.
She added that some of the deceased individuals had multiple comorbidities, such as hypertension, TB, obesity, etc.
Six cases were unclassifiable due to inadequate information available, which means investigators were unable to determine whether it was the vaccine or something else that caused the event.