Frequently asked questions about COVID-19 vaccines

Keeping the public up to date with the latest scientific data on the COVID-19 pandemic is no easy task. In a short time, the scientific community is not only generating a great deal of knowledge, but, in an exercise of transparency, it is making great efforts to transfer all this knowledge to society.

In science, before taking further steps forward, it is necessary to stop and check that everything is working correctly. These interruptions often raise doubts among the population and, in this case, in relation to the safety and efficacy of vaccines.

Below, Dr Beatriz Mothe, researcher at IrsiCaixa and doctor at the Fight AIDS and Infectious Diseases Foundation (FLS), and Dr José Moltó, doctor at the FLS, answer some of the most frequently asked questions.

EFFECTIVENESS

How effective are the vaccines and how long do they last?

These vaccines have efficacies ranging from 75-95%, which were demonstrated during clinical trials and are now being confirmed by the millions of people vaccinated worldwide.

Vaccine efficacy studies have been carried out in different contexts, so comparing them is complicated, however, they all have very high efficacy and the differences between them are more about logistics and availability than efficacy. In fact, they are more effective than the flu or measles vaccines.

Efficacy rates are measured in terms of reduced risk of symptomatic infection. Therefore, if a vaccine is 75% effective, it does not mean that out of 100 people vaccinated, 25 will become infected, but rather that the individual risk of developing a symptomatic SARS-CoV2 infection is 75% lower if you are vaccinated than if you are not. Although we do not yet have data on what will happen in a year's time, nor how effective vaccines will be against new variants that may appear, the efficacy result six months after starting vaccinations is still very high, even against most of the current variants.

Once vaccinated against COVID-19, can we transmit the virus?

Vaccine clinical trials show efficacy in preventing symptomatic infection but not the ability to transmit the virus, so this second fact cannot yet be confirmed. However, there are already several observational studies that have followed vaccinated people over time and have been able to show that the few infections that do occur are generally milder (few symptoms) and that patients have less virus in their blood (viral load), so the risk of transmitting the infection to contacts is lower. However, as the overall percentage of vaccinated people is still low, we do not know how long the protection lasts and how effective it is against the new variants. That is why vaccinated people cannot currently stop applying preventive measures, such as the use of masks and social distancing.

SAFETY

Are COVID-19 vaccines safe?

The safety of vaccines has not only been assessed in clinical trials but, subsequently, once mass vaccination is implemented, it is continuously monitored. The aim is to protect the population and ensure that the benefits always outweigh the risks.

Some of the vaccines that have been approved, when compared to other marketed vaccines (such as influenza), have a more pronounced reaction 24-48 hours after administration, but are not more dangerous. They may induce local damage and cause more general symptoms such as headache, fatigue or fever, but these are usually tolerable symptoms that are controlled spontaneously or with mild analgesia.

What about people with allergies?

Vaccination is only contraindicated if there is an allergy to any of the vaccine components, which are well known in each vaccine. If a person has previously reacted to other vaccines, safety measures such as monitoring for 30 minutes after vaccination in a controlled space are usually taken.

Can SARS-CoV-2 vaccines be less safe because they have been developed faster than other vaccines?

No. They have been developed faster because they have taken advantage of existing knowledge of SARS and MERS, they have used existing vaccine production platforms, and there has been unprecedented international investment and collaboration. All the usual phases of clinical trials have been conducted, but they have been conducted in an overlapping rather than consecutive manner, and this has allowed efficacy data to be available in a shorter time. The studies have been conducted on more than 30,000 volunteers each and involved people of different countries, ages and medical conditions. This gives us a great deal of confidence in the certainty of the data generated during the pre-approval studies. Moreover, the long-term safety data obtained months after approval of the vaccines from the volunteers in the clinical trials are backed up by data from the millions of people vaccinated worldwide. In fact, few drugs at approval have been able to generate so much safety data in such a short time. This should give us great confidence.

Should we be cautious about administering AstraZeneca's vaccine?

In recent weeks we have experienced first-hand how pharmacovigilance systems work once products are approved and start to be administered on a mass scale. These systems serve to report and analyse effects that occur after the administration of products and that have not been observed in clinical trials because they are extremely rare. The European Medicine Agency (EMA) has reported severe thrombosis cases detected after millions of vaccinations, confirming that this is a very rare potential side effect, with an estimated incidence of approximately 1 case/100,000 vaccinations. For the time being, the EMA remains of the opinion that the benefit of protection against infection, prevention of hospitalisations and, above all, prevention of severe disease, outweighs the potential risk of thrombosis, an event which, at this stage, is considered highly unlikely. It should be recalled that SARS-CoV-2 infection, apart from the respiratory effects, has a very high risk of thrombosis, including the type of severe thrombosis that has been described with AstraZeneca. Thus, the benefits still far outweigh the risks.

If we weigh the risk of thrombosis against the number of deaths or admissions for COVID-19, which way does the balance tip?

In terms of numbers, it is easy to see which way the balance tips if we compare risk and benefit, especially given the current epidemic situation and the high incidences of COVID-19. To give a numerical example, if we look at a group of 100,000 vaccinated people, there may be 0.2 cases of thrombosis caused by the vaccine but, on the other hand, 125 cases of hospitalisations in the ICU due to severe COVID-19 will have been avoided. Another very clear example is the fact that the risk of suffering a thrombotic event due to COVID-19 is close to 165,000 cases per million infected persons, whereas in the case of vaccinations this probability is estimated to be between 1-5/100,000 and 1/1,000,000,000, depending on the monitored vaccine. This is why it is very important to continue with mass vaccination, prioritising the most vulnerable people. If a specific profile of people at higher risk of suffering a rare adverse event is identified and their risk/benefit for preventing severe disease is lower, a specific recommendation could be made for this group to receive one vaccine or another.

What are the warning signs of thrombosis?

The EMA has suggested to AstraZeneca to include information on thrombosis in the product label. It has also recommended that all healthcare professionals responsible for administering the product inform the vaccinated population about symptoms consistent with thrombosis during the 5-15 days after the administration of the first dose.

Symptoms to watch out for are: choking sensation, chest pain, swelling of the legs, persistent headache that does not resolve with the usual analgesia (paracetamol/ibuprofen) or that changes with posture and/or is accompanied by a feeling of blurred vision.

Is there a treatment to avoid these side effects?

To date, no risk factors have been identified, so no preventive treatment is recommended, nor have certain age groups or people with specific pathologies been excluded. Although more cases of thrombosis have been reported in women and people under 60 years of age, it is not possible to determine a risk group, as there may be a bias due to the fact that the AstraZeneca vaccine has not been administered evenly across different age groups and that more young women have received the vaccine. In fact, in the UK, where there have been no age restrictions so far, this higher number of cases in young women has not been observed. In any case, as the mechanism by which these effects occur becomes better understood, further indications can be provided as to whether administration should be avoided in certain individuals with identified risk factors.

Is it known how thrombosis occurs and whether it can occur with other vaccines?

The mechanism behind the thromboses described so far is being intensively studied and we do not yet have a clear answer.

Some of the severe thromboses that have been described have been accompanied by a decrease in the number of platelets and identification of an excess of platelet factor 4, similar to that seen in a type of thrombosis –also very rare– that occurs paradoxically in people who are given heparin (a drug that is provided precisely to prevent thrombosis).

It usually occurs between 5-14 days after vaccine administration, which is when the immune response starts to be generated. Now, we want to find out whether the mechanisms behind these effects are related to the immune response against the vaccine vector (transporter), which may consist of either a chimpanzee adenovirus or the SARS-CoV-2 spike protein, which is responsible for generating the immune response that protects against infection.

Many other SARS-CoV-2 vaccines use the same production platform as AstraZeneca's vaccines, that is, they use different types of adenovirus, a virus that can be modified to carry material capable of activating the immune system and raising defences against SARS-CoV-2. It is therefore possible that when mass vaccination with other vaccines, such as Janssen or Sputnik, begins, similar cases may be reported (as has already started to happen with Janssen). This possible scenario would support the fact that so far no cases of thrombosis have been reported after vaccination with Pfizer or Moderna, which do not use adenoviruses in their vaccines but rely on RNA technologies. Pharmacovigilance systems and regulatory agencies will be responsible for reviewing cases and analysing the risk/benefit in each specific situation.

What happens to people under 60 years of age who have received the first dose of AstraZeneca but have had their second dose temporarily stopped?

On the principle of prudence, the State Interterritorial Council has decided to temporarily halt the vaccination of people under 60 years of age and to prioritise the vaccination of older people, as they are more at risk of suffering severe COVID-19 disease and, therefore, the benefit of vaccination is greater. It is estimated that approximately 200,000 people have received the first dose and are awaiting the second dose. A decision will be made in the coming weeks on the best option: to continue with the vaccination of the second dose, not to administer these vaccines, or to combine the first dose with a second dose of a different vaccine. In any case, it should be noted that cases of thrombosis have always been reported 5-14 days after the first dose (when the immune response begins) and not after the second dose, a fact that suggests that it is unlikely that these people who have already received the first dose and nothing has happened to them could have thrombosis if they receive the second dose, as suggested by the data of more than 33 million people vaccinated with this vaccine. Moreover, delaying the second dose of the vaccine does not affect its efficacy, but rather the opposite; several studies have shown that AstraZeneca's vaccines are more effective the longer the time between the first and second dose.

If it is finally decided not to administer the second dose to this group, it should also be emphasised that AstraZeneca confers some protection with a single dose and that the risk of severe disease is already significantly reduced.

As for combining vaccines and administering a second dose of another product, there are no studies to support this yet and it should be noted that AstraZeneca's safety, efficacy and effectiveness have been amply demonstrated after more than 33 million vaccinations worldwide.

Do vaccines modify our DNA?

No. Vaccines contain a code from which a coronavirus protein, in most cases the spike protein, can be generated. Our body recognises this protein and triggers the immune system to generate defences against the spike virus. Until now, standard vaccines inserted the entire virus, but current technology has shown that only a part of the virus is needed for the body to induce an immune system response. This code is delivered into the body by vehicles that can be either a type of genetic material called RNA, as in the case of the Pfizer and Moderna vaccines, or a virus such as a cold virus (adenovirus) carrying DNA that codes for the S protein, as in the case of the AstraZeneca, Janssen or Sputnik vaccines. None of these options integrates the content of the vaccine into our genetic material, but rather reaches the cell, manufactures the protein and degrades it.

Can the vaccine affect fertility?

There is no evidence of any effect on fertility. Normally, people of childbearing age are excluded at the start of clinical studies because it is not known what effects the vaccine may have. Animal studies have now been completed for many of the approved vaccines, and these confirm that there is no effect on reproductive organs or foetuses. There is still little clinical data in pregnant women but, so far, no problems have been reported and therefore there is nothing to suggest that the vaccines will pose a risk, either in pregnancy or in breastfeeding. In fact, many countries already recommend vaccinating pregnant women and infants in at-risk groups, and it has already been reported that vaccinating pregnant mothers causes infants to have antibodies against COVID-19 during breastfeeding.

SPECIAL GROUPS

Do people who have passed COVID-19 also have to be vaccinated?

During the first few months after COVID-19, the vast majority of people still have circulating antibodies and are possibly already protected. Even so, several cases of reinfection have been reported. To date, people who have passed the infection can wait 6 months to start vaccination. In these cases, several observational studies have reported that their immune response with one dose is comparable to that achieved by people who have not passed the disease with two doses of the vaccine. Therefore, in order to prioritise and advance vaccination, some countries recommend administering a single dose to those known to have had COVID-19.

Can immunocompromised persons be vaccinated?

Yes, vaccines are not contraindicated in immunocompromised people or people taking immunosuppressants. These are people who are at risk of passing COVID-19 in a more severe way and therefore it is a priority to vaccinate them. So far, few volunteers with these diseases have been included in vaccine clinical trials and the efficacy in this population group is still unknown, as is the case for most vaccines. As this group is vaccinated, we will know whether or not they generate the same response as the rest of the population, and whether or not they are as effective. Studies will tell us whether these people may benefit from booster doses since, due to their immune system deficiency, it is plausible that they may have a lower response to vaccination, but only long-term data will confirm this.

When will people with HIV infection be vaccinated?

Following the indications of the Interterritorial Council (5th update of the COVID-19 vaccination strategy, 30 March 2021), the start of vaccination of people with HIV-1 who are more susceptible to severe SARS-CoV-2 infection has been authorised. This population has been defined according to their immune cell levels (CD4+ cell counts of 200 cells/mm3 in the last analytical controls). In the coming days, the hospital units will be contacting the people identified in this group in order to progressively schedule their vaccination.

More information available

• https://www.nejm.org/covid-vaccine (English) 
• https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-authorised (English)
• https://www.aemps.gob.es/informa/boletines-aemps/boletin-fv/2021-boletin-fv/4o-informe-de-farmacovigilancia-sobre-vacunas-covid-19/ (Spanish)
• https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/vacunaCovid19.htm (Spanish)

Vaccines, Immunology and Pharmacology Group

Fight AIDS and Infectious Diseases Foundation
IrsiCaixa AIDS Research Institute
Infectious Diseases Service at the Hospital Germans Trias i Pujol