1.1 Why do we need a vaccine against COVID-19?

COVID-19 has shown its potential to cause a severe disease up to death impacting societies worldwide. Vaccines against COVID-19 aim to trigger an immune response specific to the SARS-CoV-2 virus causing the disease. This way, the immune system can be trained to recognise and fight the virus before its reproduction in the human body gets out of control and eventually causes severe symptoms.

This concept of vaccination is known since more than a century and ever since has successfully been implemented to protect people against polio, hepatitis and influenza, just to name a few.

1.2 How do vaccines work?

The purpose of a vaccine is to help develop immunity to an infectious agent by stimulating the immune system to produce antibodies, thus protecting against future infections.
In the case of the new coronavirus, a vaccine can make the vaccinated person less susceptible to an infection with the virus and thus the COVID-19 disease it causes. At the very least, it should make an infected person have a shorter duration of illness or fewer complications.

1.3 Why should I get vaccinated even if I am not part of the vulnerable or elderly population?

Given the current epidemiological situation, it is important to primarily ensure a protection for those who are most at risk. This includes people over 65 years of age or those who are vulnerable, particularly because of an underlying disease that increases the risk of complications or death. People at high risk to develop a severe course can be found in all age groups due the individual health condition.

However, also people not belonging to these categories can transmit the virus once they are infected, even if they might not show any or only light symptoms. The vaccination is expected to reduce the transmission of the virus and thus is an act of solidarity: When you get vaccinated, you can also help to protect everybody around you.

1.4 How many people in Luxembourg need to be vaccinated to achieve herd immunity?

The idea behind this is that if a large enough subset of the population is vaccinated, the transmission of the virus will slow down and might even come to a halt as it cannot replicate efficiently anymore within vaccinated people.

Now, it is difficult to define a threshold value at which percentage of vaccinated population this might be the case. Also, factors such as the social distance and mobility play an important role in this context. Thus, current models suggest a vaccination rate in the range of 50-70% is needed to generate herd immunity (also referred to as ‘community immunity’).

1.5 After I get vaccinated, how fast am I immunised?

The immune response to the vaccine and hence the virus develops during the first weeks following a vaccination. During that time, the immune system will generate an antibody-based immune response to a particular part of the virus. The period after which an immunisation can be assumed also depends on the type of vaccine used as some of them (e.g. those from Pfizer/BioNTech and Moderna) require a booster injection after some days to be fully efficient.

Therefore, it is important to still follow all common safety measures (e.g. wearing a mask, etc.). This holds true also if the vaccination was performed already several weeks ago as it cannot be excluded up to this point that also vaccinated people can still transmit the virus.

You can find all current safety precautions and restrictions on the government's website. 

1.6 Do I still have to wear a face mask and follow the safety measures after I got vaccinated?

At this point, it cannot be excluded that you might still be able to transmit the virus if you get infected despite being vaccinated (and thus very likely having less or no symptoms of the disease).

Until more information is available, everyone will have to keep wearing a mask and adhere to all other measures including physical distancing, even after having been vaccinated.

1.7 What are the potential side effects of a vaccine?

For every vaccine (like for any type of medication), certain side effects also may occur.

First and foremost, these effects are due to an immune reaction of the body and indicate that the vaccine is having an effect and you are developing a protection. Thus, experiencing side effects in the context of vaccinations is completely normal. Depending on the type of COVID-19 vaccine used, the side effects might also be different (your health care professional will be able to explain them to you in detail) though have generally been reported to be rather mild with symptoms such as headache, fatigue, muscle and joint pain, pain and redness around the point of injection being the most common ones.

1.8 I had a COVID-19 infection in the past and recovered. Do I still need to get vaccinated?

Yes. At the current state, there is no data available for how long someone is protected from getting COVID-19 again after infection. Early evidence suggests that natural immunity from COVID-19 may last for around 5 months, but more studies are needed to better understand this.

Therefore, it is highly recommended to get vaccinated even if you have had COVID-19 in the past. Also, there have been no reports of safety problems associated with vaccinating individuals with a history of COVID-19 infection, or with detectable COVID-19 antibodies.

1.9 Should I get vaccinated once I was tested positive to COVID-19?

In general, the vaccination is recommended for every adult person without a known counter-indication, regardless of a previous COVID-19 infection. If you have been acutely tested positive for the virus, please discuss with your treating physician about the vaccination which depends on your personal condition.

Even after recovering from a COVID-19 infection, you should still get vaccinated (see question above) to build up an efficient immune response for potential subsequent infections in the future.

1.10 How long does the immunity upon vaccination last?

No definite answer can be given yet to this question, as SARS-CoV-2 virus was unknown before the pandemic and the vaccine was developed only in the second half of 2020.

However, long-term clinical studies are currently being performed worldwide to answer the question on the length of time that immunity is ensured and if a subsequent booster vaccination may be required.

In general, today’s commonly performed vaccinations against other diseases have shown to last several years up to ensuring lifelong protection.

1.11 Is it advised and safe to vaccinate vulnerable/elderly population in general?

The vaccination aims to reduce severe symptoms of COVID-19 and its transmission in the population. As disease severity has been shown to correlate with age, specific attention is put to the elderly population. To significantly reduce the risk for vulnerable or elderly people to develop a severe infection with potential mortality, those people are advised to get vaccinated as soon as possible. In Luxembourg (as well as in several other countries), priority groups for the vaccination have been defined and this group will be, besides healthcare workers, vaccinated with the highest priority.

1.12 What will happen if not enough people get vaccinated?

An insufficient coverage of vaccination will likely lead to an enduring extension of the current restriction and protective measures which are imposing a large burden on both economy and personal life. The goal of an exhaustive vaccination is to stop the transmission of the virus among the population and thus to protect everybody’s individual health. Until this is achieved, precautional measures such as social distancing, face masks, etc. will most likely need to remain in place; however, they can only slow down virus transmission and will not completely avoid transmission. To this point, vaccination is the only realistic way to suspend such measures again when enough people are finally protected by the vaccine.

1.13 What does ‘efficacy of the vaccine’ mean?

Vaccine efficacy is determined during the final stages of the clinical trials and has been reported to be 94% and 95% for the Moderna and Pfizer/BionNTech vaccine, respectively. This value describes the percentage of patients protected against COVID-19 out of the total population vaccinated. Statistical analyses compare the results from vaccinated patients with patients having received placebo and determines whether there is a notable difference between those patients mainly in relation to SARS-CoV-2 infection and COVID-19 symptoms.

1.14 Will getting the flu vaccine protect me from getting coronavirus?

Generally, no. Despite the fact that the influenza virus and SARS-CoV-2 share similarities in terms of some symptoms, a vaccination against influenza generally will not provide an efficient protection against COVID-19. Nevertheless, it has been suggested that flu vaccine might lead to a slightly elevated protection against COVID-19 in some cases as well. It should also be noted that a co-infection with both the SARS-CoV-2 and influenza virus is possible which has shown to cause a more severe progression of the disease.

However, as every vaccine is specifically designed for a particular virus, only the newly developed COVID-19 vaccines can trigger a specific immune response to build up a protection against that virus.

1.15 I recently got another vaccine; can I get vaccinated now against COVID-19

In general, there are no major issues over getting different vaccines within a couple of days. These days, some vaccines are even commonly administered in combination, such as the DTP-vaccine (diphtheria, tetanus, pertussis). However, it is advised to make a plan with your physician if you are getting many different vaccinations (e.g. before travelling to a tropical country) in order not to overwhelm the immune system and ensure efficiency of the vaccination. As for the COVID-19 vaccines, please consult your physician if you received another vaccination recently and e.g. are still feeling weak.

1.16 Can I choose which vaccine to receive among those approved by the EU? 

The choice of vaccine is made on the basis of the medical history and medical tests carried out by the vaccinating doctor. It is important that patients answer the questions asked, when making appointments and during the vaccination, in a detailed and honest manner, to ensure that the doctor can make the appropriate choice.

1.17 Who will be vaccinated when?

In Luxembourg, the COVID-19 vaccination strategy is based on dividing the population in different risk groups based on their age and previous medical conditions.

Phase 1: currently ongoing

Phase 2: starting 1 March 2021 

2a - Persons from the age of 75 years, starting with the elderly 

2b - People who are highly vulnerable due to a pre-existing health condition:

• Trisomy 21, adults 
• Solid organ transplants, including those on a waiting list 
• Haematopoietic stem cell transplant, during the first 6 months or under immunosuppressive treatment 
• Cancer and malignant hemopathy under treatment (chemotherapy, radiotherapy, immunotherapy) 
• Congenital immune deficiencies 

Phase 3 

3a - People aged 70-74, starting with the oldest 

3b - People who are significantly vulnerable due to a pre-existing health condition:

• Acquired immunodeficiency 
• People taking immunosuppressive drugs, biotherapy and/or long-term corticosteroid therapy in immunosuppressive doses 
• HIV infection with CD4 < 200/mm3 
• asplenia, functional or not 
• Severe chronic respiratory disease 
  • Severe chronic obstructive pulmonary disease (COPD), GOLD stages 3 and 4, group D*. 
  • Cystic fibrosis 
  • Severe chronic pulmonary fibrosis 
  • Severe extrapulmonary restrictive pathology, with or without ventilatory assistance. 
  • Severe uncontrolled asthma (level 5 according to GINA)§ corticosteroid-dependent (under oral corticosteroid therapy) 
• Severe cardiovascular disease : 
  • heart failure stage NYHA III or IV# 
  • unstable coronary artery disease 
  • cardiomyopathy 
• Major neuro-cognitive deficit (MMS° score < 20) 
• Chronic renal failure on dialysis 
• Cirrhosis at stage B or C of the Child-Pugh classification 
• Morbid obesity (body mass index > 40 kg/m2) 

Phase 4

4a - People aged 65 to 69 (starting with the oldest) 

4b - People who are moderately vulnerable due to a pre-existing health condition:

• Diabetes with or without insulin, with cardio-neurovascular complications 
• Complicated high blood pressure, with sequelae of stroke or associated heart disease 
• Neuromuscular disease with clinical repercussions 

Phase 5

5a - People aged 55-64, starting with the oldest 

5b - Persons with a health condition that may expose them to increased risk:

• Balanced diabetes, without complications 
• Uncomplicated high blood pressure 
• Obesity (body mass index 30-40 kg/m2) 

Phase 6

6a - Precarious people, living in communities, and not previously vaccinated because of their vulnerability and other people who are particularly exposed to infection as a result of their activity 

6b General resident population between 16 and 54 years of age, starting with the oldest, not previously vaccinated due to vulnerability .

Find more information in the Luxembourg COVID-19 Vaccination strategy:

• Categorisation
• Les phases de vaccination (Infographie)

2.1 How many vaccines are currently on the market? How many are under development?

As of 8 February 2021, two vaccines were approved by the European Medicines Agency developed by Pfizer-BioNTech and Moderna. The effectiveness of the vaccines has been reported to be up to 95% which is similar to the characteristics for established vaccines.

In addition, more than 60 different vaccines are currently tested in clinical studies out of which several candidates can be expected to complement the currently available landscape.

More detailed information on all currently developed vaccines can be found on the website of the WHO.

2.2 What types of vaccines exist?

In general, there are three different mechanisms of action for vaccines:

• Injecting the inactivated virus or parts of it
• Use another non-replicating carrier virus to convey harmless parts of the genetic information of the virus of interest
• RNA/DNA vaccines not using a carrier-virus to introduce the blueprint for isolated and therefore harmless parts of the virus

In all three mechanisms, the cells of the immune system will be activated by the presentation of so-called antigens (virus proteins) at their surface. These either come from the injection itself or are produced by cells of your body (in the case of using carrier virus or RNA/DNA). The presentation of the antigens will then trigger and activate the immune system leading to a proactive immune response.

2.3 How do the different COVID-19 vaccines work?

comprehensive graphical visualisation published in Nature

Please note: It is important to remember that you cannot get COVID-19 directly from the vaccines that will be offered, as none of them contain the full and active virus.

Injecting inactivated virus or virus protein (e.g. Sinovac vaccine from China)

The classical way is to inject a chemically or thermally inactivated form of the virus or parts of it which are taken up by specific immune cells. The components of the virus are broken down within the cell into smaller fragments. These fragments, also called antigens, are then attached to a specific molecule called the MHC-II which is sent to the surface again. Here, it literally displays the antigen fragment of the virus to the other cells of the immune systems, primarily the T-cell, which will initiate a chain of reaction resulting in the production of antibodies against the particular antigen.

As a virus consists of many different parts/proteins, it cannot be predicted against which part the immune reaction will be generated. Compared to other types of vaccines, the immune reaction might thus be weaker and require regular boosters to stimulate the immune system. None of the COVID-19 vaccines currently approved in Europe use this technology (status 14 January 2021).

Using a carrier-virus to transport the blueprint of the antigen (e.g. Sputnik-V from Russia and AstraZeneca vaccine)

In this method, a carrier-virus which is not able to replicate itself is genetically modified to encode the genetic information for a particular antigen of the pathogen (e.g. of the SARS-CoV-2 virus). Commonly, adenoviruses are used for this purpose which will be taken up by the cells of the immune system and thereby bring the genetic information for a certain antigen into the cell. Here, a messenger-RNA (mRNA) encoding the antigen is produced by the cell which subsequently will be used to produce the antigen itself. This will then be used to display it at the surface for the cell, as described above.

This type of vaccination is well established and widely used as a standard for vaccinations against tuberculosis, influenza, Ebola and several others.

RNA/DNA vaccines (e.g. Pfizer/BioNTech and Moderna vaccine)

The difference in this type of vaccines is that they do not rely on a carrier-virus to introduce parts of the genetic information of the pathogen. Instead, the DNA or RNA serving as a blueprint for the antigen is directly introduced into the cell encapsuled in a lipid coat. Just as for the other types of vaccines, the subsequently produced antigen is presented on the surface of the cell triggering an immune response.

2.4 Can vaccination prevent the transmission of the SARS-CoV-2 virus?

Up to now, this question cannot be definitively answered yet. According to Pfizer, its scientists were looking for ways to assess the transmission of the virus in future studies.

Moreover, AstraZeneca and Oxford University are addressing the question whether a vaccine can protect against transmission of the virus. Although they have not yet published full results, their trial has routinely tested participants for SARS-CoV-2, allowing researchers to know whether people were infected without developing symptoms after previously getting vaccinated. It is expected that vaccinations might also reduce the transmission of the virus due to reduction of the symptoms; however, there is not enough data available at the moment to make a conclusion on this (status 8 February 2021).

2.5 Is a COVID-19 vaccine only beneficial for society if it will stop transmission?

Currently, it is not yet clear to what extend the COVID-19 vaccination results in sterilising immunity, i.e. not only prevent disease but also prevent the virus replication and thereby transmission. Research studies are underway to answer this question.

History has shown however that even vaccines that don’t block transmission entirely have beneficial effects for society. Certainly not all vaccines for other diseases on the market today for produce sterilising immunity, we rather see a spectrum. For example:

• Hepatitis B vaccines do not reduce replication of the virus. Still, in many countries it is recommended to vaccinate newborns to prevent this serious illness. More than 1 billion people have been vaccinated by now against Hepatitis B worldwide which led to a significant reduction in prevalence of the disease (e.g. 68% in the US).
• Rotavirus vaccines only reduce but not prevent replication of the virus. Nevertheless, the resulting reduction in viral load makes a transmission less likely: 4-10 years after introduction, Rotavirus infections dropped by 74-90% in the US.
• Flu vaccines are also not truly sterilising in the respiratory tract. Even though only about 50% of adults get vaccinated against the flu, flu vaccines have been shown to reduce hospitalisations among older adults by an estimated 40 percent and intensive care admissions of all adults by as much as 82 percent.

2.6 What is the benefit for young people to get vaccinated then?

Even though it is not yet known if COVID-19 vaccines can prevent transmission, vaccinating young people is beneficial for society for the following reasons: 

• Even though young people are less likely to suffer from strong complications after SARS-CoV-2 infections, some young people need hospitalisation or even end up in ICU. In Luxembourg for example, people between 20 and 50 years of age constitute 16,6% of all people hospitalised in normal care and 15.2% in the ICU (status 25 January 2021). If we were only to vaccinate old people and then relax the sanitary measures, the virus could still go around a lot and we would still risk that subsequent higher numbers of infections among young people will burden the healthcare system and risk the death of some young people.
• Also, it should be considered that about 10% of all people infected experience what is called “long COVID”, meaning that they have effects of Covid-19 that continue for weeks or months beyond the initial illness. Lasting symptoms of coronavirus can include fatigue, breathlessness, pain, not being able to think straight or focus (‘brain fog’), which often leads to absence from work and certainly reduced quality of life. In addition, COVID-19 can increase the risk of blood clots and thereby lead to deep vein thrombosis, heart attacks and stroke also after the infection. Such phenomena have also been observed in young people.
• Both of the complications mentioned above trigger healthcare costs far above those of a vaccine. But more importantly, it currently cannot be predicted who is at risk of developing the two types of complications.

Considering the high efficacy and safety of the currently approved COVID-19 vaccines, vaccinating of a big as possible proportion of society is the best we can do at the moment to get the pandemic under control.

2.7 What does the “m” in the mRNA vaccine stand for? 

The mRNA is an abbreviation for ‘messenger ribonucleic acid’ which is part of the basic protein synthesis machinery in all organisms including humans.

Briefly, the genetic information is stored in the nucleus in the form of DNA (not to be confused with RNA!). To translate this information into a protein performing a particular function, first a copy of the particular part of the DNA (also called ‘gene’) is made. This copy is made out of messenger RNA – or short mRNA – and transfers the blueprint out of the nucleus to the plasma of the cell, hence the term. There, a cellular process called translation uses the mRNA to build the protein, encoded by the genetic sequence of the RNA.

Thus, the production of protein from mRNA is a very basis phenomenon in nature and higher life would not be possible without it.

In other words, one could compare the DNA to a library of cookbooks, the RNA to a photocopied page of a recipe (in order not to damage the book) and the protein to the dish that you make from the recipe.

2.8 Can mRNA change or interfere with our genetic information?

No. The mRNA fundamentally differs from DNA and is thus not able to integrate into the human genome or to interfere with it. In addition, the human DNA resides in the nucleus where it is also protected from external influences; therefore, the mRNA can also physically not come into contact with the DNA.

Moreover, mRNA (unlike DNA) is not very stable and is broken down by the human body quite fast (which is also one reason why certain mRNA vaccines have to be cooled all the time).

However, some viruses (such as HIV) are able to integrate their genomic information which is based on RNA into the genome of their host by producing DNA from it. SARS-CoV-2 is lacking all the required enzymatic machinery for this process, thus mRNA derived from the SARS-CoV-2 virus will not be able to initiate such a process.

2.9 How have the current COVID-19 vaccines been tested?

As it is common practice for all vaccines in general, also the vaccines against COVID-19 have been tested in large clinical studies. The inclusion and exclusion criteria for these studies vary from study to study; generally, people recruited for these studies are healthy adults, both men and women.

The approvals for the vaccines have only been given after the appropriate phases of the clinical studies have been successfully conducted according to international regulations as for any other medication.

2.10 What about the vaccines previously developed and released in Russia?

The Russian vaccine termed ‘Sputnik V’ is based on a carrier-virus (adenovirus) to introduce the blueprint for a SARS-CoV-2-antigen. The manufacturers claim an efficiency of up to 90%; however, clinical trials have not been fully completed yet. Nonetheless, the vaccine has been started to be administered in some countries including Russia but has not been approved by the European Medicines Agency (EMA) yet.

2.11 How likely are mutations of the virus? Can this make the virus evading the vaccination effects so that the vaccine is not effective anymore?

Generally, RNA viruses such as SARS-CoV-2 are constantly mutating. In most cases, such mutations will not change the composition and structure of the virus or might even cause the virus to be inactive. Most mutations are thus observed in non-essential regions of a virus’ genetic material causing it to still function as before.

In some cases, a mutation might change a critical region of the virus causing an alternative protein to be produced. If the mutation by chance occurred in the small part of the protein serving as an antigen for the vaccines, this might have an effect on the efficacy of the vaccines – as the antibodies produced might not recognised the protein as good as before.

To circumvent this, typically several antigens are used in parallel to create alternative and redundant immune responses. A simultaneous mutation in all of these antigens and consequently a complete evasion of the vaccine-induced immunity is statistically highly unlikely. In addition, the newly developed mRNA vaccines could also be adapted rather quickly to adapt the immune reaction to the mutated form of the virus.

Yet, mutations constitute a permanent property of the virus enabling it to repeatedly change its properties. This highlights again the importance of stopping the spread of the virus to contain the situation as fast as possible.

2.12 What about the new mutated version of SARS-CoV-2 from the UK? Does vaccine work as well in this case?

According to recent studies, there is no evidence that the current vaccines do not work against the British variant of the coronavirus. However, as mutations in RNA viruses occur frequently, it might happen that a mutation in the future also influences the efficacy of the vaccination, either lowering or improving it.

2.13 Is the spike protein, which serves as target protein (antigen) for the vaccine, unique to the SARS-CoV-2 or does it also occur naturally in the human body? Thus, is the immune reaction is specific to only eliminate the virus and not attack parts of the human body?

Virus proteins are serving a certain function, such as making contact with its host cell and initiating the internalisation into the cell. For SARS-CoV-2, the so-called spike protein performs these tasks and therefore is also in the focus for many vaccines. The current vaccines target several parts of this spike protein to enable the immune system to recognise it. This redundancy ensures that the spike-protein is also detected as a pathogenic protein if parts of it change due to mutations.

In turn, the human body does not share this type of molecule as both its functions and structure differ from the molecular mechanisms in the human body. The antibodies produced after a vaccine can hence not attack parts of the human body, but will specifically attack the virus upon infection.

In comparison with other viruses, the individual parts of the virus are used to classify the virus and also determine its unique properties. Therefore, the protein composition of a virus also constitutes its uniqueness and thus the vaccines against one particular antigen are specific for that virus.

2.14 Can long-term effects of the vaccine be predicted? 

Based on common scientific evidence, there are no severe long-term side effects to be expected specific for the currently available SARS-CoV-2 vaccines.

Typically, side effects are minor and occur directly after the vaccination disappearing after a few days the latest. Therefore, vaccinated people are requested to stay in the vaccination centres for a short period of time after they received the vaccination to ensure their well-being.

2.15 What is the vaccine composed of?

The major component of all COVID-19 vaccines is water where the active and adjuvating agents are solubilised. The active agent is either a set of mRNA-strands enclosed in lipid droplets (Moderna and Pfizer/BioNTech vaccine) or a modified carrier-virus (AstraZeneca). Adjuvating agents such as polymers, sugars and salts help to stabilise the vaccine and ensure its efficiency.

No animal products or parts are included in the vaccine.

2.16 Will the vaccination also help against the mutated variants of SARS-CoV-2? 

This depends a lot on the particular mutation, but in general the protection provided upon immunisation will not vanish entirely even against mutated variants. 

As of 18 February 2021, several mutations of the new coronavirus have been discovered. Among the most frequently discussed mutations are the B.1.1.7-strain, also called ‘UK variant’ and the B.1.351-strain, referred to as ‘South Africa variant’. Studies investigating the efficacy of the vaccines against these variants are still ongoing, however the current consensus is that the vaccines have the same efficiency towards the UK variant, whereas they might be somewhat less efficient against the variant from South Africa. Notably, both mutations have been suggested to increase the transmission of the virus itself, which highlights again the importance to immunise the population quickly.

As mutations are typically only altering a small part of the virus, antibodies might still be capable to detect the virus to some extent, so the vaccination still has an effect. This article describes the relation between the current mutations and vaccine development. 

2.17 Which adenovirus stains are used by the AstraZeneca vaccine?

AstraZeneca uses the modified chimpanzee adenovirus ChAdOx1 as a vector to deliver the blueprint to build the spike protein (further information can be found in the EU Clinical Trials Register).

This vector is currently used for both the first and the second injection. Indeed, in individual who have already developed antibodies against this particular vector-type, the vaccination might be somewhat less efficient. Therefore, other vaccines such as the Russian Sputnik V rely on two different vectors in the subsequent injections. Currently, AstraZeneca and the developer of the Russian vaccine join forces to exchange the vector being used and to make the vaccine even more efficient.

Further information on the AstraZeneca vaccine can be found on the website of the European Medicines Agency.

2.18 Why should also the AstraZeneca vaccine be used?

All vaccines currently on the marked, including the one from AstraZeneca, provide a comparable and substantial protection against severe cases of COVID-19. The AstraZeneca vaccine relies on a different mechanism to generate an immune response and has shown to be less efficient in preventing mild courses of COVID-19. However, it shows several other advantages (transport at moderate temperatures, higher stability, etc.). To offer protection to as many people as possible, the parallel use of several vaccines is inevitable for ending the pandemic. 

3.1 How can I be sure that the vaccines are safe?

All COVID-19 vaccines are being developed following the same legal requirements as other types of drugs. Like for all medications, effects of COVID-19 vaccines are first tested in laboratories (cells and animal models), then, in a later phase, they are tested in human volunteers. There are several stages of human testing which are referred to as phases of clinical trials. At each stage, they have to pass many tests to enter into the next phase until they finally can get approved by the European Medicine Agency:

Pre-clinical testing:
The developed vaccine is tested in the laboratory using cell cultures or animal models. Efficacy, toxicity and pharmacokinetics are addressed at this point. No testing on humans is performed until the preclinical testing is completed.

Clinical testing - Phase 1:
Healthy volunteers are recruited to test the safety of the drug. Different doses are tested, and the possible dosage of the vaccine is assessed. Adverse effects are very closely monitored in this stage.

Clinical testing - Phase 2:
Volunteering patients (usually several hundreds) are recruited to test the efficacy of the drug. Side effects are closely observed with regards to the mechanism of action of the vaccine.

Clinical testing - Phase 3:
Several hundreds to several thousands of volunteering patients are participating in two groups. One group will receive the new vaccine whereas the other group receives the standard-of-care treatment or a placebo if there is no alternative vaccine available. Only if the tested vaccine has proven a significant improvement in treatment and passes all safety criteria, approval by the authorities can be given.

Clinical testing - Phase 4:
This phase is conducted after approval of the vaccine during the subsequent years. The occurrence of rare side effects is monitored. It should be noted that vaccines are generally not expected to have any long-term effects.

3.2 Why was the development and approval so fast and doesn't this compromise the security?

A notable observation for COVID-19 vaccines is the speed of their development. A potential approval is accelerated due to the public health emergency and comprehensive amount of previous knowledge due to the SARS epidemics in 2002/2003.

The vast number of infected people also allowed to quickly recruit a sufficient number of participants into the study, which is often a bottleneck in clinical testing.

Thanks to a rolling-review process, the review procedures for approval of the drug could be initiated faster than usual to evaluate data from companies in the shortest possible timeframes. At the same time, new scientific information and results from the clinical studies was constantly exchanged, ensuring that all necessary safety measures were met which are also imposed on other vaccines.

A more detailed explanation can be also found below in the section ‘context of research’ or in the interview with Prof. Rudi Balling

3.3 How is the approval process performed and by whom?

For Europe, the approval of vaccines is done by the European Medicines Agency (EMA). This YouTube video describes the process of approval by the EMA. Further information on medication and vaccine approval can be found on the website of the EMA.

You can find more detailed information on how vaccines and other medicines are evaluated and authorised in the EU also on the website of the EMA.

3.4 Which side effects are known for the vaccination?

As for most other vaccinations, common side effects such as redness, swelling or pain around the injection site have been reported. In addition, fatigue, fever, headache or aching limbs might occur during the first three days after vaccination. Such reactions are usually mild and disappear after a few days. In fact, they reflect that the body is reacting to the vaccine indicating the mounting of an immune response.

In isolated cases, also allergic shocks have been reported. These affected people had reported other severe allergies prior to vaccination and were successfully treated against the allergic shock. This phenomenon is currently being investigated in depth, despite the fact that those were single cases and the overall benefit of the vaccine still clearly outweighs it potential risk.

It should also be noted that allergic reaction to vaccines have also been observed in the part and can be ascribed to the adjuvants in the vaccine (such as stabilising agents) rather than to the active substance itself.

If you are have had allergic reactions in the past, your physician might give you advice on this topic and inform you on the current state of scientific evidence.

3.5 How are (long-term) secondary effects of vaccines evaluated?

All vaccines and medicine undergo pharmacovigilance surveillance after they have been approved, for instance by the European Medicines Agency. These often lasts for years.

How this will be done for the COVID-19 vaccines can be found on the European Medicines Agency's (EMA) website.

The plan comprises for instance new reporting obligations for companies that will have to submit monthly safety reporting summaries in addition to the regular updates foreseen by the legislation. Furthermore, the plan details the scientific studies already in place to monitor the safety, effectiveness and coverage of COVID-19 vaccines after their authorisation. Lastly, it details the exceptional transparency measures set up by EMA as well as how the Agency plans to engage with a wide range of stakeholders. 

3.6 When do side effects of vaccines usually occur? 

Typically, side effects as described above occur the same day up to a few days after the vaccination. Usually, such effects are comparably mild and indicate the onset of an immune reaction. As side effects typically only occur within minutes after the vaccination, people are requested to stay at the vaccination centre for a short while after they received the injection. This way, potential allergic reactions can directly be noted and readily treated easily.

Long-term effects of vaccinations are typically not known for the common vaccination techniques used. As the mRNA vaccines are using very similar adjuvants compared to well-established vaccines, there is so far also no reason to assume any long-term effect of this class of vaccine.

3.7 Can any effects occur in the long run after the vaccination?

Long-term effects of vaccinations are typically not known for the common vaccination techniques used. As the mRNA vaccines are using very similar adjuvants compared to well-established vaccines and the mRNA itself breaks down quickly after having completed its purpose, there is so far also no reason to assume any long-term effect of this class of vaccine.

3.8 What is the risk of auto-immune disease when using vaccines?

To date, none of the numerous vaccines investigated in clinical studies have been shown to cause autoimmune diseases. Such diseases occur when the human body mounts an immune reaction against itself. Some diseases such as multiple sclerosis or diabetes might cause such an autoimmune reaction.

However, the vaccines used to trigger the immune response against a pathogen usually cause a very defined immune reaction which so far has not been shown to induce autoimmunity for any approved vaccine. Nonetheless, researchers still investigate the potential of new vaccines to cause autoimmunity.

To date, none of the numerous vaccines investigated in clinical studies has been shown to cause autoimmune diseases. Such diseases generally occur when the human body mounts an immune reaction against itself. Some diseases such as multiple sclerosis or diabetes might for instance cause an autoimmune reaction. However, the vaccines are used to trigger the immune response against a pathogen and thus usually cause a very defined immune reaction which so far has not been shown to induce autoimmunity for any approved vaccine. Nonetheless, researchers still investigate the potential of new vaccines to cause autoimmunity.

3.9 Should pregnant or breastfeeding women get vaccinated?

Pregnant and breastfeeding women have not been included in COVID-19 vaccine trials conducted for approval. Currently, researchers are studying potential effects specific for women belonging to these groups. Until these studies have been concluded, it is unclear if the immunisations would be safe for their use in pregnant or breastfeeding women.

More information on the vaccination procedure in Luxembourg can be found on www.covid19.lu

3.10 Should children get vaccinated?

The currently approved COVID-19 vaccines (status 14 January 2021) have not been authorised for children below 16 years of age as they have not yet been included in the clinical trials for approval of the vaccines.

One of the reasons for this is that the appropriate dose for children of different age groups still need to be determined. As for other medication, children should not simply receive the same amount of vaccine as adults and the appropriate dose needs to be tailored to their state of development. Generally, an adjusted vaccination for children is also expected in the future as COVID-19 can also seldomly take a severe course in children.

3.11 Can the COVID-19 vaccination affect fertility?

There is no scientific evidence that the vaccination can affect fertility in any way. The vaccination triggers the production of a viral protein which will induce an immune response. As this response is very specific, it generally does not affect proteins of the human body which differ in both composition and function.

3.12 Should people with chronic or idiopathic allergies get vaccinated? 

For some people with reported allergies in their medical history, the vaccination was causing an allergic reaction within minutes after the injection. However, in a systematical study from the Center for disease control (CDC), out of 1.89 million people only 21 developed severe allergic reaction which could all readily been treated. 

The individual question if a person with allergies should get vaccinated depends on the particular person and should be discussed with your treating physician. 

More information on safety characteristics can be found in our interview with Prof. Dirk Brenner. 

4.1 How many injections will I get and how long do they have to be apart from each other?

The number of necessary injections will depend on the type of COVID-19 vaccine. The majority of vaccines currently available will require two injections with a gap of 3-4 weeks between each injection. These specific intervals have been determined in clinical studies in order to optimise the immune reaction.

The medical professional performing the vaccination can give you all more information depending on the type of vaccine used.

4.2 When and where can I get vaccinated?

The population of Luxembourg will be vaccinated according to different levels of priority to which everybody has been assigned to according to age, profession and other factors. Every resident will receive a letter via mail with a personalised code which can be used to book an appointment in the national vaccination centre within two weeks.

The appointment (as well as the follow-up appointment) can be booked via covidvaccination.lu. More information on the national vaccination strategy can be found here: covid19.lu

4.3 Why is the vaccination done in a vaccination centre and not at my treating physician?

At the moment, the amount of available vaccine is very limited, and it is not yet available on the public market. Like other countries, the government of Luxembourg therefore will administrate the vaccine in centralised centres.

Moreover, the different vaccines require to be stored at cold temperatures (as low as -80 degrees), which might not simply be feasible for general physicians.

4.4 How can I be sure that the cooling chain and hence the vaccine is intact?

As the vaccine is centrally stored and administered, the strict observance of the cooling chain will be insured by the authorities. The highest care will be taken to ensure that only vaccines will be administered that were stored and transported according to the specific requirements keep the cooling chain uninterrupted. 

4.5 How do I report if I’ve had a particularly bad reaction after receiving the COVID-19 vaccine?

If you experience side effects after the vaccination beyond the common reactions described above, please consult your physician or pharmacist.

If you experience adverse side effects to be directly related to the vaccine, you can also report them directly via the national reporting system.

4.6 Can cross-border worked get vaccinated in Luxembourg? 

As of 18 February 2021 cross-border workers can be vaccinated in Luxembourg if they are health professionals. The government has defined all other vaccination phases for residents only based on criteria relating to the age and vulnerabilities. Please refer to the government website for more information.

4.7 Will the University organise vaccination on campus?

Currently, vaccination in Luxembourg is only organised at specialised vaccination centers. As of 18 February 2021 cross-border workers can be vaccinated in Luxembourg if they are health professionals. The government has defined all other vaccination phases for residents only based on criteria relating to the age and vulnerabilities. Please refer to the government website for more information. 

5.1 Why was the vaccine developed so fast whereas research of treatments for diseases such as cancer, Parkinson’s or Alzheimer’s take decades of work and are still not finished?

It is correct that commonly the de novo development of a drug or vaccine takes several years of research and clinical studies. However, there are multiple reasons why this process was significantly sped up in the case of the COVID-19 vaccines:

• The knowledge on the design and development of efficient vaccines is available since many decades. Moreover, also the mechanism of immunity upon an infection has been well studied. This constitutes a fundamental different situation to disease where the exact cause so far remains elusive such in the case of neurodegenerative diseases or many types of cancer and chronic diseases.
• The global threat of the virus quickly became evident. Thus, an enormous amount of resources and manpower was united already in the beginning of 2020 to start the development of a vaccine
• Already during the outbreaks of SARS-CoV-1 and MERS-CoV in 2002 and 2012, respectively, research on vaccines against those viruses was conducted. Although the SARS-CoV-2 virus causing COVID-19 is somewhat different, also the other two viruses belong to the family of coronaviruses. Specifically, the respective counterparts of the SARS-CoV-2 spike protein which is now the major target for most vaccines have been extensively studied before. Research could thus tremendously profit from previous experience of developing vaccines against coronaviruses.
• Technically, developing a vaccine against the SARS-CoV-2 virus is relatively easy, compared to other viruses such as HIV. Therefore, fast progress could be made as also the financial resources were readily provided by research institutions and governments worldwide. An exceptionally high level of cooperation between private and public partners had let to the development of more than 260 vaccine candidates within several months which all have to pass the common regulatory and safety test before approval. However, the sheer number of potential vaccines also increases the likelihood of discovering a successful candidate.
• In exceptional cases, a ‘rolling review’ procedure can be used which means that authorities can already access the data on the vaccine while the clinical trial is still running. This does not mean that the vaccine will be approved without clinical trials, but the bureaucratic procedure for approval can be started somewhat earlier and thus the whole process can be accelerated.
• The immediate thread towards the population also has led to an unusual high number of volunteers to participate in clinical studies. Together with an increasing number of infections within the population, this allowed to conduct the clinical trials in the fastest timeframe possible and allow thorough observation of potential side-effects.

Even with such an accelerated vaccine development, all new COVID-19 vaccines must meet the same safety standards to be licensed in the European Union, just like all other vaccines.
You can find more information on the website of the EMA.

5.2 Have there been other Coronaviruses before?

Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two illnesses caused by coronaviruses closely related to SARS-CoV-2. Researchers began developing vaccines for these diseases after their discovery in 2003 and 2012. However, they never made it past the early stages of development and testing, mainly due to a lack of interest as the viruses disappeared rather soon after their outbreak. However, this earlier vaccine research has been very helpful for the COVID-19 vaccine development process.

Also, several other comparable harmless variants of coronaviruses are known which cause the common, typically without any long-term consequences.