Questions and answers on covid-19 vaccines
The medicines agencies in the EU and around the world collaborate on the authorisation and monitoring of covid-19 vaccines. Once the vaccines have been authorised, drug regulatory authorities follow up on them by monitoring side effects. Read more in our questions and answers on covid-19 vaccines.Questions and answers
Who has authorised the vaccines?
In Europe, it is the Committee for Medicinal Products for Human Use, CHMP, which has thoroughly examined and approved the vaccine manufacturers’ data and documentation. Under the European Medicines Agency, EMA, the CHMP has then prepared a recommendation to the European Commission, which is the body formally authorising the vaccines and issuing conditional marketing authorisations.
What does a conditional marketing authorisation imply?
The fact that the marketing authorisation was conditional in the first period means that the vaccine manufacturers were only allowed to market their vaccines on the condition that they had to continuously submit updated data on the vaccines’ efficacy and safety.
The vaccine manufacturers were also required to continue their vaccine studies based on which the authorisation was granted. This means that the many thousands of people who participated in the clinical trials have been monitored to ensure the authorities could continue receiving data about the persons who were the very first to receive the vaccine. In this way, the companies contribute to the health authorities’ and the scientists’ combined knowledge of the vaccines’ efficacy and effectiveness.
For how long is the conditional marketing authorisation valid?
The conditional marketing authorisation expires after one year, following which the vaccine manufacturers can apply for a renewal. When the vaccines have been on the market for a longer time, the vaccine manufacturers can apply for a full marketing authorisation.
The EMA website shows when the various vaccine manufacturers were granted a conditional marketing authorisation, when the authorisations were renewed and when they have received full marketing authorisation: COVID-19 vaccines: authorised | European Medicines Agency (europa.eu). The two vaccines used in the Danish vaccination program both received full marketing authorisation in October 2022.
The vaccines’ efficacy
How effective are the vaccines?
When the first vaccines for COVID-19 were developed in 2020, the efficacy of the vaccines were studied and documented in major drug trials with tens of thousands of participants. The two vaccines that are used in Denmark demonstrated a very high efficacy of 94% and 95%, respectively. In other words, the vaccines protected 9 out of 10 against COVID-19 infection.
Back then, the efficacy was measured in relation to infection with the initial virus variant (the Wuhan variant). The virus has since mutated many times, and we have regularly seen new variants that have proved to be more contagious than the original virus variant. This influences how effective the vaccine is at preventing infection with corona. Having said that, the vaccines still provide a high protection against severe illness and death.
For how long does the vaccine protect against disease?
The protection from the vaccine is best in the first months after the basic vaccination (two jabs). After four to six months, the effect wears off but may be increased with a booster vaccine.
Researchers, vaccine manufacturers and health authorities continuously monitor for how long the vaccine efficacy of each vaccine lasts, and a booster vaccination is offered when it is considered necessary.
Do the vaccines protect against new virus variants?
The vaccines have so far proved to be resistant to the various virus variants and mutations that have emerged in Denmark, including the Omicron variant. However, the original vaccines’ efficacy against infection with new variants is lower than it was for the original variant (the Wuhan variant). That’s why the vaccine manufacturers develop versions of the vaccines to also target the Omicron variant.
Why are the vaccines updated to new variants?
The updates to the corona vaccines are much like the annual updates of the seasonal influenza vaccines. Like corona, influenza is a highly contagious virus disease for which vaccines are available; and like coronavirus, influenza virus can mutate so that new virus variants emerge over time. The influenza vaccines are therefore updated annually to include new variants before the flu season starts. This is done to ensure they offer optimum protection against exactly those flu variants that are expected to dominate in that season. The COVID-19 vaccines have been variant-updated in the same way to provide better immunity to the known virus variants in the winter of 2022/23.
Prior the 2023/24 winter season, a new update of the covid-19 vaccine from Pfizer/BionNTech has been approved. It has been approved by the EU Commission on 1 September 2023:
Adapted COVID-19 vaccine for autumn vaccination compaigns * (europa.eu) after it had been assessed and recommended by the EMA: Comirnaty: EMA recommends approval of adapted COVID-19 vaccine targeting Omicron XBB.1.5 | European Medicines Agency (europa.eu).
The COVID-19 vaccines target the spike protein, the surface protein of the coronavirus. The spike protein is foreign to the immune system, which makes the body produce protecting antibodies when it encounters the spike protein through the vaccine.
The spike protein looks different from virus variant to virus variant. So when an update is made to a vaccine, it is the appearance of the spike protein that is changed. The first-generation corona vaccines are based on the spike protein of the original coronavirus variant that started the pandemic in December 2019 (the Wuhan variant). But the next-generation vaccines will be based also on the spike protein of the Omicron variant. This way, it will be easier for the body's immune system to recognise and fight the virus variants that are responsible for today’s spread of infection.
How are the vaccines updated?
Proteins (including the spike protein) consist of amino acids, and there are about 20 different amino acids. You can compare it to a string of 20 beads in different colours and shapes. Depending on which beads (amino acids) are on the string, the appearance of the string of beads (the protein) can change. That's what happens when the vaccines are adapted to the spike protein of the Omicron variant.
Except for the change in appearance of the spike protein, the next-generation vaccines will have exactly the same composition as the original COVID-19 vaccines. The variant-updated vaccines therefore do not need to be authorised all over again; a so-called ‘variant-updated authorisation’ is sufficient. The process is similar to how influenza vaccines are updated to new variants and authorised every year before the flu season.
How are the updated vaccines authorised?
Both Pfizer/BioNTech and Moderna, the vaccine manufacturers behind the vaccines included in the Danish vaccination programme, have updated their vaccines, and from June to September 2022, the European Medicines Agency, EMA, has conducted rolling reviews in which the vaccines’ underlying data have been examined thoroughly.
The vaccine manufacturers were required to document that their variant-updated vaccines were just as good or better than the original vaccines in terms of stimulating the production of protective antibodies. In other words, the vaccines must protect just as well or better than the original vaccines. The manufacturers also had to document that they can produce variant-updated vaccines of the same high quality as those already marketed.
The formal process is this: Once the EMA’s Committee for Medicinal Products for Human Use, CHMP, has finished its rolling review, the companies submit a variation application for consideration by the EMA. If the documentary evidence can be approved by the scientific experts, the EMA will recommend the European Commission to grant a marketing authorisation for the updated vaccine.
How the vaccines work
Is the protection the same for everyone?
The vaccines do not protect everyone as well. Your health and age play a part in the protection you will get from the vaccine. When the vaccines’ efficacy is measured to see for how long the protection lasts, the target groups having received the vaccines must be taken into account. Older people or people with a weakened immune system are likely to experience a lower effect compared to younger and healthy people. That’s why these groups are offered one more booster vaccination by the Danish Health Authority.
Are people contagious after vaccination?
The SSI (Danish State Serum Institute) has assessed that vaccinated people are less likely to transmit infection than people who are not vaccinated. But fully vaccinated persons can still transmit the virus to others. So it is still important to follow the advice about distancing and maintaining good hand hygiene regardless of whether you are vaccinated.
Read more at SSI about the risk of transmitting the virus to others.
Should people with allergies turn down vaccination due to the risk of allergic reactions?
People with allergies can generally be vaccinated, unless they have a known allergy to the vaccine’s active substance or one or more of its adjuvants (“helping agents”). If you know that you are allergic to something, your doctor can help you decide if you should have the vaccine.
Allergic reactions to COVID-19 vaccines occur in very rare cases. This is no different from other vaccines. That is why healthcare professionals are present when you are vaccinated and why you are asked to wait for 15 minutes before leaving the vaccine centre.
Is the vaccine safe during pregnancy?
Yes, the vaccines are safe during pregnancy. This is shown in the European Medicines Agency’s review of comprehensive studies with 65,000 pregnant women. The review did not find any sign of an increased risk of miscarriages or pregnancy complications in mothers or their unborn babies. Nor has the monitoring of reported side effects in Denmark found any connection between the vaccines and spontaneous abortion. Read the summaries of product characteristics of the individual vaccines for further details. Read more about reported suspected side effects here. Pregnant women who are infected with COVID-19 have a higher risk of severe illness. The Danish Health Authority therefore recommends pregnant and breast-feeding women to be vaccinated.
Can the vaccines affect fertility?
No. There is no indication that fertility is affected by the COVID-19 vaccines. Completed animal studies have shown that there are no vaccine-related effects – neither on the female animals’ fertility and pregnancy nor on the foetus’ development before or after birth. Nor has the monitoring of vaccines used in humans shown any effects on the fertility of men or women.
Can people who have a weakened immune system due to illness be vaccinated?
Yes, but the protection could be lower for those with a weakened immune system. That is why the Danish Health Authority recommends a booster dose for people with a weakened immune system.
Are there any types of medicines that you should take cautiously in connection with vaccination?
If you are on so-called immunosuppressive treatment (used, for example, by cancer and transplant patients and in some cases patients with auto-immune disease), this could in some cases target that part of the immune system that should be responding to the vaccine. In these cases, individual specialist medical advice and a special vaccination procedure may be required. Certain medicines/treatments also imply that you cannot have injections into a muscle (e.g. strong blood-thinning treatments).
If you have been told that you cannot have injections into a muscle, this applies also to the COVID-19 vaccine. If you are on ordinary blood-thinning medication, you can have the COVID-19 vaccine.
Is there DNA in COVID-19 vaccines?
Yes. Very small amounts of residual DNA may be present in vaccines (and in other medicines where DNA or other biological material has been used in the manufacturing process). This also goes for the mRNA vaccines.
The mRNA vaccine technology simulates the natural process occurring in the body when the cells are building proteins: Our DNA, present in the cell’s nucleus, is by the cells in our body transcribed to messenger RNA (mRNA). mRNA is transported from the nucleus to the cell fluid where the so-called ribosomes build the protein which the mRNA encodes for.
In the same way, lab-made mRNA is used in the vaccines to tell the body’s cells what the corona virus’ spike protein looks like so that the body may build the spike protein triggering an immune response to COVID-19.
In the lab, the code for the spike protein is first inserted in a plasmid DNA. The plasmid DNA serves as a memory disc recalling what the protein looks like. Plasmids occur naturally in bacteria and are used because they are easy to work with. They have been used in pharmaceutical manufacturing since the 1980s.
Plasmid DNA is also used to manufacture the mRNA encoding the spike protein. Finally, the DNA template is broken down and removed from the vaccine, but it is inevitable that tiny DNA fragments will remain in very small amounts.
That is why the WHO and the drug regulatory authorities many years ago introduced maximum limits for the amount of residual DNA allowed in products. And pharmaceutical manufacturers must document that their manufacturing processes are capable of keeping residual DNA at very low limits. The manufacturing process must also apply active controls showing that the accepted DNA limits are kept.
It is only probable in theory and completely unlikely that these very small amounts of residual DNA in vaccines are capable of entering the body’s own DNA. Firstly, the amount is so small that it would be difficult even to enter the cell and next the cell’s nucleus. Secondly, biological mechanisms are required for vaccine residual DNA to enter our DNA that is not even present in our body.
Do the vaccines cause side effects?
All medicines could have side effects; the COVID-19 vaccines are no exception. But it is essential that the side effects caused by the vaccines are not worse than the symptoms and the disease that the vaccines are designed to prevent. So, the risk of serious side effects must not be higher than the potential risk of falling ill.
What side effects have we observed for the COVID-19 vaccines?
The most common side effects of the COVID-19 vaccines used in Denmark are generally mild or moderate in nature and improve or disappear within a few days. These would include:
- Pain and swelling at the injection site
- Muscle and joint pain
In rare cases, the vaccines could cause serious side effects. This could be severe allergic reactions, including so-called anaphylactic reactions or cases of inflammation of the cardiac muscle.
The known side effects of the individual COVID-19 vaccines are listed in the product information (package leaflet and summary of product characteristics) for each of the vaccines.
Who can report side effects?
Both healthcare professionals and people in general can report suspected side effects to the Danish Medicines Agency. Only a suspicion is needed to report. You can make a report even if you only suspect the symptoms to be caused by a vaccine – you do not have to be sure that there is a connection between the two. It is not necessary to report it or contact your doctor about common mild and harmless side effects such as discomfort, redness at the injection site, mild fever and muscle soreness, but it is important that you do if you experience something serious or unexpected which you are unable to explain by something other than the vaccine.
In the first two years after a vaccine has been put in use, doctors, dentists, prescribing pharmacists and midwives must report any suspected side effects (except suspected side effects caused by medication errors) for patients they are or have been treating to the Danish Medicines Agency. After this period, the reporting obligation only applies to suspected serious or unexpected side effects.
The Danish Medicines Agency provides regular updates on Danish reports of suspected side effects of the COVID-19 vaccines in use. Read more about the side effects reported for the vaccines.
How do we assess if a suspected side effect is caused by the vaccine?
The Danish Medicines Agency reviews the reported symptoms and accompanying information and assesses if the symptoms can be explained by other factors or if the vaccine is the most likely contributor to the symptoms. All reports are registered in a database of side effects. The reports are used to monitor if there are signals of new or changed risks associated with the vaccines that call for further investigations.
What will the Danish Medicines Agency do if it turns out that one of the vaccines have possible new risks?
If we or another drug regulatory authority in the EU/EEA discovers a signal pointing to new or changed risks of one of the vaccines, e.g. a new possible side effect, a known side effect that is more serious than expected, or a known side effect that occurs more frequently than expected, we will request the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) to start a thorough investigation of the signal.
If these investigations confirm that new or changed risks are related to a COVID-19 vaccine, this could lead to a revision of the product information of the COVID-19 vaccine, a change to who the vaccine can be given to, or even a suspension or withdrawal of the vaccine’s marketing authorisation.
The vaccines are authorised by a marketing authorisation issued by the European Commission. Based on statements by the EMA’s Committee for Medicinal Products for Human Use, CHMP, the European Commission makes decisions on the change, suspension or withdrawal of a marketing authorisation. The Pharmacovigilance Risk Assessment Committee, PRAC, advises the CHMP on matters of pharmacovigilance. The Danish Medicines Agency has representatives on the CHMP and PRAC.
Could the COVID-19 vaccines cause side effects not occurring before a longer period of time?
At present, there is no scientific evidence that the authorised COVID-19 vaccines may lead to late sequelae in the form of side effects occurring a long time after vaccination. Nor has a signal been raised with the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) on possible late sequelae in the form of side effects occurring a long time after vaccination.
Based on the vaccines’ composition and the knowledge available about the vaccines, there is no reason to suspect that side effects could occur a long time after vaccination.
The drug regulatory authorities in Denmark and the other EU countries continue to monitor the COVID-19 vaccines for as long as they are marketed – just like they do with other medicines.
Can side effects persist for a long time?
If you experience symptoms that persist for a long time, the first thing you should do is contact your doctor for an examination. If the doctor can find no other explanation than the vaccine, your doctor, or you, can report it as a suspected side effect.
The Danish Medicines Agency is continuously reviewing the reported side effects and assesses if there is cause for raising a safety signal. So far, no signal has been raised about long-term courses with common side effects such as fever, tiredness and headache with the Pharmacovigilance Risk Assessment Committee (PRAC).
Is compensation available if you experience side effects or long-term effects?
As with other types of medicines, you may be entitled to compensation from the Danish Patient Compensation Association.
Do manufacturers of COVID-19 vaccines have the same liability towards European citizens as they have for other types of medicines?
The contracts on the procurement of COVID-19 vaccines negotiated by the European Commission with vaccine manufacturers on behalf of the EU member states are fully compliant with the EU legislation and the directiveonproduct liability.
The rules on product liability makes no difference to the individual patient, the reason being that patients in Denmark have the right to compensation for rare and serious side effects regardless of whether the manufacturer is held liable for a product defect. It is the state that pays compensation to the patient, and the state can subsequently assess if it will file a product liability claim against the manufacturer to cover the costs of compensation.
Are menstrual disorders acknowledged as a possible side effect of COVID-19 vaccines?
In October 2022, the European Pharmacovigilance Risk Assessment Committee (PRAC) completed its review of menstrual disorders, concluding that heavy menstrual bleeding should be added as a possible side effect to the product information of the COVID-19 vaccines from both Pfizer/BioNTech and Moderna.
Vaccine product information:
There are no data suggesting that amenorrhoea (absent periods) could be caused by vaccination, nor does anything suggest that menstrual disorders in connection with COVID-19 vaccination can affect fertility or pregnancy.
Can inflammation of the cardiac muscle and inflammation of the membrane around the heart occur after COVID-19 vaccination?
Inflammation of the heart muscle (myocarditis) and inflammation of the membrane around the heart (pericarditis) are known side effects of the COVID-19 vaccines from Pfizer/BioNTech and Moderna. The conditions are therefore described in the product information for the two vaccines.
These to inflammatory conditions can occur in very rare cases after vaccination. Symptoms can vary but often include breathlessness, a forceful heartbeat that may be irregular (palpitations) and chest pain. The PRAC has concluded that the risk of getting inflammation of the heart muscle or of the membrane around the heart is less than 1 out of 10,000 vaccinated people.
Is there a link between the inflammatory condition MIS and COVID-19 vaccination?
The Danish Medicines Agency has reviewed two reports on the rare inflammatory condition known as MIS (multisystem inflammatory syndrome) after vaccination with the Pfizer/BioNTech COVID-19 vaccine. A few cases of MIS after vaccination have also been observed in other countries.
Based on the first Danish report received in August 2021, the Pharmacovigilance Risk Assessment Committee (PRAC) decided to investigate the possibility of a causal relationship between MIS and the four COVID-19 vaccines. In October 2021, the PRAC concluded that there was insufficient evidence on a possible link between COVID-19 vaccines and MIS.
Is the occurrence of side effects different from vaccine batch to vaccine batch?
No. The Danish Medicines Agency has studied the relationship between the number of side effect reports and the vaccine batches that the reports relate to. Our analysis shows that significantly more reports per 100 doses were reported for the first vaccine batches used early in the vaccination programme compared to later in the vaccination programme.
The first vaccine batches were relatively small compared to those used later on, but the analysis shows that the size of the vaccine batches is not a significant factor in relation to the number of reports. However, the time when the individual vaccine batches were used in the vaccination programme is a decisive factor. The analysis raises no suspicion that the safety of the various COVID-19 vaccine batches used in the Danish vaccination programme has been different.
Read more in this analysis of COVID-19 batches and side effects (PDF)