Coronavirus Update FAQ 12

This is the twelfth of a series of Covid-19 newsletters from FDIME (Foundation for the Development of Internal Medicine in Europe). The aim of the newsletters is to present qualified answers to the public, specifically on issues in which internists have a saying.
FDIME is a non-profit organizations, which aims to improve medical care for patients in Europe and has several activities promoting medical research and medical education of young European specialists in internal medicine. FDIME supports young internists to attend the European School of Internal Medicine, participate in the European Exchange program and also provide grants for research in Internal Medicine.

1. Antibodies/Protection after Covid 19 infections and after vaccination
   Author: Daniel Sereni, France

Take home message:

Antibodies produced after complete Covid vaccination prevent the infection by the virus: in a small percentage of vaccinated people an infection may occur, but the vaccine protects them against severe disease and death.

Immunity after natural Infection:

After an infection by the Covid 19 virus, the disease is usually mild but may also be extremely severe and lead to death. Some people may have no symptom at all (up to 50% of cases).
Whether the symptoms have been non-existent, mild or severe, we will develop immunity against the virus. It means that we are protected against a new infection by the same virus for several months or maybe even years.

Immunity after vaccination:

What we expect from vaccination is protection which is at least long-lasting and potent. How does it work and what are the limits in the case of Covid 19 virus and its variants? The principle of vaccination consists in introducing a non-infectious portion of the virus in our body. Some vaccines use a new concept developed for Covid 19: they stimulate our cells to produce the part of the virus that will be targeted by the vaccine.

Whatever the vaccine mode, our immune system will develop a defensive reaction in response to the foreign molecules. But more importantly, it will keep the information in memory. Then, if we are in contact with the virus our immune system will recognize the germ and fight it. The weapons we use are our immune cells and finally the antibodies. You hear more about antibodies because their level and activity are much more easily monitored (by blood tests) than those of the immune cells. It takes in average two weeks to achieve a complete immunity after either one or two shots depending on the type of vaccine.

Is protection 100% efficient?

No vaccination achieves a 100% protection. In the case of marketed Covid 19 vaccines the protecting antibodies are found in 90 to 95% of fully vaccinated people. They remain at a high and protective level for at least six months, and probably longer. However, a small percentage of vaccinated people may still be infected: fortunately, most of these cases do not develop severe disease.

Covid 19, like most of the viruses is constantly mutating, with new variants being identified worldwide. One of the questions raised by the spread of these variants is their susceptibility to present vaccines. What has been observed at this moment, based on the follow-up of hundreds of millions of vaccinated people is that variants are not resistant to antibodies produced through vaccination. Nevertheless, some studies show that the protection provided by infection or by vaccination becomes less effective with time particularly when people are exposed to variants.

To compensate this possible attenuation of immunity against variants, several solutions exist. For example, a third vaccine shot has been recommended in some European countries, 3 to 6 months after the second one in order to raise the level of protective antibodies. This recommendation, however, is not widely accepted, which may partly relate with the call from the WHO to reserve these additional doses for third world countries.

A long-term solution is to develop more broadly effective vaccines. All companies producing Covid 19 vaccines are working on making modifications to their vaccine to rend it more effective against variants.

2. How effective are the vaccines with new variants of covid 19?
   Author: Jan Willem Elte, The Netherlands

Take home message:

Although Covid 19 variants are more infective/contagious/transmissible than the original strain, most current vaccines are still effective (however, slightly less).

About the vaccines:

Only a year after the start of the Covid 19 pandemic, the scientific community have developed, after swift and thorough research, a number of highly effective vaccines against COVID-19.

The most frequently used vaccines in Europe are two m-RNA vaccines PfizerBionTech and Moderna and two vector vaccines AstraZeneca and Janssen. In some European countries the vaccine Sputnik V, a vector vaccine is also being used.

The vaccines were meant to combat the original strain, as first detected in Wuhan, China and have proven to be very effective in most circumstances. However, since then many variants have originated and the question is whether these vaccines are as effective against these variants, as they are the original virus strain.

About the variants:

The variants are often more infective/contagious/transmissible than the original strain, and can also cause more illness, though not necessarliy a higher mortality.

It is speculated that now there are already thousands of variants of COVID-19. In Europe, however, the most frequent encountered variants are:

1. Alpha (UK)
2. Beta (South Africa)
3. Gamma (Brazil)
4. Delta/delta + (India)

Most variants show changes in spike proteins, with which the virus can attach themselves to the cell more easily. As mentioned, the fear is that variants are more transmissible, less sensitive to the vaccines and may cause more serious disease. This is, however, uncertain and limited research shows that most vaccines seem effective (although slightly less than for the original virus) against most of the variants up to now. An exception is the South African variant (Beta), which is less sensitive for the AstraZeneca vaccine. However, Novavax (or Covavax), a nanoparticle vaccine, is effective in South Africa.

Vaccination (and Covid 19 itself) gives rise to the formation of specific antibodies, but also to the rise of helper T cells, both leading to immunity. At this moment the Delta variant is the most prevalent virus in large parts of Europe.

More virus infections means more mutation and this increases the importance of vaccination even more. Besides, basic public health measures remain extremely important: physical distancing, wearing masks, hand washing, staying at home if unwell are all common sense. The use of a third shot of vaccine three (or more) months after the second dose to ensure longer lasting protection, is now being considered.

For the future there are three options:

• Change the composition of vaccines (is not difficult; most companies are already redesigning vaccines)
• Combine different vaccines ( also combined with influenza virusvaccine, which is already possible with Novavax)
• Annual Covid 19 vaccination, such as with influenza

3. What about vaccination of immunocompromised patients against covid-19?
   Author: Loïc Guillevin, France (loic.guillevin@orange.fr)

Take home message:

Immunocompromised patients should be vaccinated with three shots of Covid 19 vaccine because of hyporeactivity. The preferred vaccine to be used for the the third shot (boost) four weeks after the second dose is a mRNA vaccine.

Vaccination:

Vaccination has been proven to be the most effective tool to prevent the spread of infectious diseases. In Europe, 65% to 80% of the population has received at least one anti-COVID-19 vaccine injection. However, some questions have been raised concerning patients with primary or secondary immune deficiencies, as well as those with autoimmune diseases or any disease associated with modification of the immune system. These patients are thought to be at increased risk for severe COVID-19 infection.

Vaccines:

Several vaccines directed against SARS-CoV-2 are available in the European Community and have been approved by the European Medicine Agency: 2 messenger RNA (mRNA) vaccines: Comirnaty^® (BioNTech-Pfizer) and Spikevax^® (Moderna); and 2 recombinant vaccines: Vaxzevria^® (AstraZeneca) and Ad26.COV2-S by Jansen (Johnson & Johnson).
Inactivated nucleic acid and protein-subunit vaccines are deemed safe, while special precautions are needed for live-attenuated vaccines. All vaccines authorized in Europe to prevent COVID-19 do not transmit the virus. Moreover, it has been shown that vaccines directed against SARS-CoV-2 do not trigger flares of underlying immune-system–associated diseases rendering individuals immunocompromised.

Immunocompromised patients:

Scientific and professional Learned Societies unanimously recommend vaccinating patients with altered immune systems: autoimmune diseases (treated or not), patients taking corticosteroids, immunosuppressants and/or biotherapies. Pertinently, administration of immunosuppressive or immunomodulating agents should not be delayed or discontinued at the time of vaccination.
The major question concerns the ability of these immunocompromised patients to produce antibodies specific to SARS-CoV-2, especially those who are being or have been treated with drugs depleting B- and T-lymphocyte subpopulations. Anti-B-cell monoclonal antibody treatment of lymphoproliferative disorders and autoimmune diseases induces severe and lasting B-cell depletion, which markedly reduces the production of specific anti-SARS-CoV-2 antibodies, thereby limiting vaccine efficacy. Chronically hemodialyzed patients and transplant recipients (bone marrow or solid tumors) have lower anti-SARS-COV-2 antibody synthesis than immunocompetent controls. Indeed, anti-SARS-CoV-2 antibodies have been detected in less than 10% of immunocompromised patients after 2 injections.

Vaccination of immunocompromised patients:

For that reason, Health Authorities recommend vaccinating immunocompromised patients with a schedule adding a third vaccine inoculation, administered 4 weeks after the second. That supplementary dose should be given as a function of the response to the first two injections. It is likely that the third dose will boost hyporeactivity to the vaccine. To further increase vaccination efficacy, an mRNA vaccine is the preferred type, even for patients who had received a first shot of the AstraZeneca or Jansen vaccine.
Should an immunocompromised patient without a sufficient immune response after vaccination be exposed to SARS-CoV-2, prophylactic administration of Ronaprev (casirivimab and imdevimab) could be considered and has been prioritized by Health Authorities.