Can Covid vaccines have long-term effects?

Vaccination against Covid is accelerating with the extension of the health pass. But for some, fears about possible long-term side effects of vaccines, especially RNA (Pfizer and Moderna), persist. What are the effects observed today? How soon do they occur? Are there any risks to DNA? Developed with Dr Benjamin Wyplosz, the infectious disease doctor.

What do we know about the side effects of Covid vaccines today?

At the time of placing on the market, not all adverse drug-related reactions are always known, especially rare adverse reactions (1/1000). "Some rare or very rare side effects may only appear when millions of people are vaccinated," the EMA confirms. This is now the case of vaccines against Covid. According to Johns Hopkins University, more than 3 billion doses of these vaccines have been administered worldwide as of July 12, 2021 (60 million in France). According to the ANSM, the percentage of adverse reactions observed at the end of June 2021, i.e. 6 months after the start of the vaccination campaign in France (out of 51 million doses injected at that time), is 0.08% for Comirnaty (Pfizer-BioNTech), 0.11% for Spikevax (Moderna), 0.31% for Vaxzevria (AstraZeneca) and 0.03% for Janssen (Johnson*Johnson). For Dr Benjamin Wyplosz, infectious disease doctor at the Chu de Bicêtre, there is no need to worry: "We have surveillance systems around the world including in France. These are the most monitored vaccines since the history of vaccination. If there were any serious adverse reactions found and not listed, people would complain about them on the Internet and social networks.' Regarding the cases of thrombosis reported after vaccination with the AstraZeneca vaccine, or the cases of myocarditis and pericarditis* with the Pfizer and Moderna vaccines "these are the only adverse effects observed, they are exceptional and they occur within 15 days after vaccination" recalls the infectiologist who stresses that "the Covid virus itself can give myocarditis".*145 cases of myocarditis and 138 cases of pericarditis have been reported among people who received Comirnaty on 31 May 2021 in Europe out of approximately 177 million doses injected; 19 cases of myocarditis and 19 cases of pericarditis were with Moderna's vaccine out of 20 million doses administered in Europe. The EMA acknowledged in July 2021 that these heart conditions can occur in 'very rare cases' after vaccination with these two sera and recommended the addition of these new side effects in their product sheet.

How quickly do adverse reactions to a vaccine occur?

"Since the beginning of the history of vaccines, we have never seen adverse reactions occurring more than 15 days to 3 weeks after vaccination" informs the infectiologist. At most, effects can occur within 2 months of vaccination reports Professor Mathieu Molimard, head of medical pharmacology at Bordeaux University Hospital in a Tweet on July 5. The most sceptical will advance the cases of multiple sclerosis linked in the 1990s to vaccination against hepatitis B or cases of autism associated with the measles vaccine or macrophage myofasciitis with vaccines containing aluminium... "All suspicions occurring after the 2-3 week delay has been refuted by scientific research," says Dr Wyplosz. We have proven that it does not exist. The effects of a vaccine occur at the moment when immunity is established, i.e. Within 15 days.'

Can RNA vaccines alter DNA?

The principle of the RNA vaccine is not to inject the virus so that the body develops antibodies against it, but only molecules of RNA (an acid chemically very close to DNA) or DNA of this virus that codes for the formation of the Spike protein in the context of the coronavirus. It is this protein that allows the virus to enter the cells of the body. During the injection, the cells that will receive the RNA will produce the proteins of the virus that will end up on the surface of the cells.

The immune cells will then consider these cells as foreign and destroy them. Faced with this mechanism of action, concerns have emerged about a possible 'edge effect' of RNA capable of penetrating cells and modifying the INDIVIDUAL's DNA. However, the RNA injected via the vaccine has no risk of transforming our genome or being transmitted to our offspring as long as it does not penetrate the nucleus of the cells (and does not go to the cells of the reproductive organs). However, it is in this cell nucleus that our genetic material is located," explains Inserm. In addition, the cells producing the Spike protein following the injection of the vaccine are quickly destroyed by the immune system. Foreign RNA, therefore, does not stay in the body for long: it produces just what it takes to train the immune system to react in the event of 'natural' infection by the virus before being eliminated.

Is there not still a lack of hindsight on these vaccines?

Thanks to the logistical and financial resources committed by countries around the world, Covid vaccines have been approved by health authorities in less than a year. A delay that seems short and can worry, those reluctant to vaccinate. "The vaccine has been evaluated according to the usual standards but there are many obstacles that have been lifted in advance to the development of a vaccine against a pandemic," argues Dr Wyplosz. For example, the time to obtain authorizations to launch clinical trials has been accelerated, modern data entry techniques have been employed. Many people quickly volunteered to participate in the trials, and the rolling review method was employed by drug review agencies, which made it possible to approve the first vaccines more quickly. Instead of waiting to have compiled all the data from manufacturers relating to therapeutic trials, health agencies were able to receive this data as they went along and decide more quickly on their validation or not upon receipt of the latest results.

Pfizer's Comirnaty vaccine has been validated by the EMA after a Phase 3 trial in 44,000 people
Moderna's Spikevax vaccine was tested on 30,000 people before being validated by the EMA.
AstraZeneca's vaccine was tested in 4 clinical trials conducted in the UK, Brazil and South Africa 24,000 people before been approved in Europe by the EMA.
Johnson's single-dose vaccine was tested via a clinical trial of 44,000 people in the United States, South Africa and Latin America before the EMA.

Related: Covid-19: babies are born immune thanks to their mother's vaccination

'How long would it take to reassure people?'

Health authorities continue to carry out safety and efficacy studies after the authorization of vaccines as well as the companies that market them in order to provide new information (duration of protection, against new variants of the virus, safety, long-term benefit, etc.). "How long would it take to reassure people? Asks Dr Wyplosz. Hundreds of millions of people have been vaccinated for almost a year and there are no reports of serious adverse events. If you continue to be worried and you are in hyperbolic anxiety, there is nothing we can do about it because the worry will always persist. But if you are in scientific anxiety you should be reassured in view of these figures. ' In addition, with RNA vaccines, we administer a harmless natural protein of the virus that is not able to fuse with our cells while the virus makes it produce proteins that are inserted into our cells. Is it better to be reassured by a harmless protein made by the vaccine or by a virus that infects us? On the one hand, we have the virulent virus and on the other, we have a vaccine administered to hundreds of millions of people for whom there is no serious signal. If we put the two in balance, the virus is dangerous, the vaccine is not even in people not at risk of a severe form of Covid'.

The long-term adverse effects of Covid, forgotten?

The fear of long-term adverse effects of Covid vaccines may slow down the transition to vaccination while these effects are not demonstrated today. This is not the case for the long-term adverse effects of a Covid infection, classified under the term Covid long, and which are well documented. According to figures from the Ministry of Health as of February 2021, 50% of people who have been infected with Covid have a symptom after 1 month, and 10% of these same people are still affected after 6 months. But 'the long Covid affects people without health problems who find themselves with the disabling adverse effects of a chronic disease that we do not know how to treat. We do not know how to treat chronic headaches, chronic fatigue, loss of smell' recalls the infectious disease doctor. Before stressing that "if we can catch Covid by being vaccinated, we are infinitely less at risk of making clinical forms of the disease and in particular chronic forms".

Thanks to Dr Benjamin Wyplosz, infectious disease doctor at the CHU of Bicêtre in the Val-de-Marne.