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Vaccines Prevent SARS-CoV-2 Infections - Uncertainties and Implications

The widely used vaccines against COVID-19 also seem to prevent the initial infection with the SARS-CoV-2 virus for the most part. This good news is currently in waves from Israel and the United Kingdom to Germany. In the past week, several data on the effectiveness of the BioNTech / Pfizer vaccine BNT162b2, but also the AstraZeneca vaccine AZD1222, became public. When viewed together, they show: In addition to severe courses and deaths, the vaccines also effectively prevent infections with SARS-CoV-2. The data thus support what scientists have already suspected: People who have been vaccinated are less likely to be infected with the virus and consequently are less likely to pass it on.

However, the studies that have become public to date differ from one another in terms of their informative value and provisionality - the first results were only confidential to a few media, several preprints that have not yet been scientifically assessed have now appeared [I] [II], but also some data from large analyzes in specialist journals such as "The New England Journal of Medicine" [III] or "The Lancet" [IV]. Many of the analyzes are based on data from national vaccination campaigns and are therefore eagerly awaited observational data from real life. On the one hand, they therefore include many more people than, for example, the meticulously planned clinical studies, but they are also subject to greater potential for bias.

The data published so far give hope that vaccines will also help to contain the pandemic in the short term, in addition to the effect of relieved health systems. However, how long this protection - especially against infections with SARS-CoV-2 - lasts is still the subject of research. This is particularly relevant because the human body's immune response to a vaccination differs from that to a natural infection. SARS-CoV-2 penetrates the body primarily through the airways and their mucous membranes. There, in particular, the body initially reacts to the virus and builds up its own immune response of the respiratory tract - the mucosal immunity - [V] [VI]. Vaccinations via an injection into the muscle - as they are currently used - primarily develop antibody protection in the blood of the vaccinated person. How these differences are reflected is not yet clear [VII].

These uncertainties about how efficiently the vaccines actually prevent further transmissions also flow into the debate about vaccination passports as free tickets for certain areas of life that are currently still restricted or are also relevant to the question of which vaccination prioritization should be pursued. We therefore asked experts which aspects they pay particular attention to when it comes to protecting against infections and have compiled arguments from virology, infectiology and ethics.

Overview

     

  • Prof. Dr. Marylyn Addo, Head of the Infectious Diseases Section at the Center for Internal Medicine, University Medical Center Hamburg-Eppendorf (UKE)
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  • Prof. Dr. Carlos A. Guzman, Head of the Department of Vaccinology and Applied Microbiology, Helmholtz Center for Infection Research (HZI), Braunschweig
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  • Prof. Dr. Gérard Krause, Head of the Epidemiology Department, Helmholtz Center for Infection Research (HZI), Braunschweig
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  • Prof. Dr. Frank Dietrich, holder of the Chair for Practical Philosophy, Institute for Philosophy, Heinrich Heine University Düsseldorf
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  • Prof. Dr. Anke Huckriede, Professor of Vaccinology, Institute for Medical Microbiology, University of Groningen
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  • Prof. Dr. Verina Wild, holder of the professorship for ethics in medicine, University of Augsburg
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Statements

Prof. Dr. Marylyn Addo

Head of the Infectious Diseases Section at the Center for Internal Medicine, University Medical Center Hamburg-Eppendorf (UKE)

This statement comes from the press briefing on the next generation of vaccines against COVID-19 on February 23, 2021.

“We have waited a long time for these data that show whether there is protection against asymptomatic infection. And these are the first numbers that suggest that. Most of the data comes from preprints and we must certainly evaluate them again very critically, even if we have them completely available. But what is being transported at least now, about 90 percent protection against infections, that is actually more than we had hoped for. And if we can use the vaccine to influence the infectiousness, i.e. the protection against infections, not just the protection against illness, then that is of course a very important step for the infection process. "

“At the moment we are vaccinating very old age groups or highly exposed groups in Germany, and we are trying to reduce deaths, serious illnesses, intensive stays, etc. in order to protect the health system. So far it has not been clear that there is actually an influence on the infection rates. But of course we hoped that the vaccination would also reduce the infections. "

“Our previous vaccines against non-respiratory pathogens naturally create protection against infections, for example with measles. If we can now also protect against SARS-CoV-2 infections, then we can also influence the infection process in a completely different way, drive it down with more vaccinations and hopefully get out of the pandemic even faster. So it's really very important data. "

Prof. Dr. Carlos A. Guzman

Head of the Department of Vaccinology and Applied Microbiology, Helmholtz Center for Infection Research (HZI), Braunschweig

“These data are very encouraging and suggest that, in the short term, we can expect the vaccines currently in use to provide varying levels of protection against symptomatic and asymptomatic infections, which is vital in combating the COVID-19 pandemic. However, we must be extremely careful in extrapolating their ability to reduce viral infections and transmissions over the medium and long term. First, these vaccines do not use a mucosal route of administration (Administration through the mucous membranes; editor's note) used. Therefore, we cannot count on the induction of a robust local immune memory in the airways. Second, neutralizing antibodies circulating in the blood that migrate into the airways are likely to provide only partial protection against infection through local virus neutralization and subsequently reduce the amount and duration of virus shedding. One could therefore assume that as soon as the antibody levels in the blood decrease, we will observe a vaccine-, vaccine- and time-dependent reduction in protection against the infection. This would likely lead to some level of viral shedding after infection, in vaccinated people who are still effectively protected against symptomatic COVID-19 disease. "

"For vaccines other than COVID-19, there is no consensus on the minimum duration of protection and it is even not possible to carry out tests to assess the level of protection if it cannot be assumed that all vaccinated persons are protected, as is the case with hepatitis B Vaccines is the case. However, the following points make a solid, scientifically sound implementation of a vaccination pass for SARS-CoV-2 and COVID-19 difficult - i.e. to create a document that precisely defines how long a person is protected or does not pose a risk to others. First: It is still unclear how long protection against disease lasts after vaccination and which vaccines, to what extent and for how long, protect against infection and viral transmission. In this context, the passage of circulating antibodies into the airways described above is likely to contribute to partial protection against infection. However, as soon as the antibody levels in the blood decrease, a time-dependent decrease in protection against infection can be expected. In addition, we are missing a previously undiscussed correlate of protection - a kind of indicator - that could differ depending on the vaccine design. "

Prof. Dr. Gerard Krause

Head of the Epidemiology Department, Helmholtz Center for Infection Research (HZI), Braunschweig

To the questions to what extent the vaccination strategy would have to be adjusted based on the new data:
“The statements of the STIKO are still applicable in this regard and should not be questioned prematurely. A vaccination and the related strategy should primarily prevent illness and death. "

Prof. Dr. Frank Dietrich

Holder of the Chair for Practical Philosophy, Institute for Philosophy, Heinrich Heine University Düsseldorf

"If the risk of transmitting the SARS-CoV-2 virus is significantly reduced by the vaccination, there is the possibility of giving preference to people with many contacts, such as teachers. This could be an important component in the strategy to reduce the number of infections and effectively contain the infection rate. However, the primary goal in determining the vaccination sequence should not be to lower the seven-day incidence. Rather, the primary aim must be to prevent particularly serious illnesses with possible fatal consequences. Consequently, it is still right to give particularly vulnerable population groups, especially people of a very old age, priority when vaccinating. However, the aspect of effectiveness can play an important role in regulating access to vaccines that are not approved for particularly vulnerable population groups. For example, when it comes to awarding the vaccine from AstraZeneca, it makes sense to give preference to people who are particularly exposed at work and who cannot avoid a high number of contacts. "

“Restricting individual freedoms requires strong justifications. It is true that protecting other people from being infected with a life-threatening disease can legitimize government coercive measures. If the present results for the prevention of virus transmission by the BioNTech vaccine are confirmed and confirmed for other vaccines, the vaccinated persons do not pose a serious risk. This means that there is no longer any valid argument why the freedoms of vaccinated people must be restricted further. The question of whether the entire population has already had the opportunity to receive vaccination is irrelevant for the lifting of restrictions. The supposed dissatisfaction of not yet vaccinated people who have to wait longer for their freedoms to be regained is not a plausible reason to withhold possible freedoms from vaccinated people. The increase in willingness to vaccinate, which leads to the prospect of an earlier return to a 'normal life', also speaks in favor of lifting restrictions on freedom for vaccinated persons. "

Prof. Dr. Anke Huckriede

Professor of Vaccinology, Institute for Medical Microbiology, University of Groningen

“Such epidemiological studies from Israel and the UK are what we need now. The data from these studies are very encouraging that using vaccines in real life can prevent infections. We can learn a lot from this data, because it will take a while before we are as far as Israel, for example. "

“Before vaccine development really started, scientists assumed that vaccines could also prevent infections and thus the transmission of viruses. Then interim results from rhesus monkeys suggested that the vaccines could protect the animals from the lung disease, but the viral load was still similar in the event of an infection. Since then, the concern has been that there could well be a difference in the effectiveness with which vaccines can prevent the disease or its transmission. However, it is very difficult to measure the latter. An AstraZeneca vaccine clinical study investigated this endpoint, but these data were still preliminary. "

“It would also be important to investigate how the immune response of vaccinated and convalescent people changes over time. For example, one could also use the antibody response of vaccinated persons to see whether they have come into contact with SARS-CoV-2 in the meantime. The mRNA vaccination only induces antibodies against the spike protein, a natural infection would also produce antibodies against, for example, the N protein of the virus. "

“It's also important to keep in mind that the quality of the immune response to intramuscular vaccination is different from that of a natural infection. A vaccination mainly induces antibodies that circulate in the blood and not - like an infection via the respiratory tract - antibodies, especially IgA, which are found in the tissues of the upper respiratory tract and can neutralize the pathogen directly on site. Although some of the antibodies are also transported there from the blood, vaccines administered via the respiratory tract would certainly be more suitable to build up good, so-called mucosal immunity. These have also been the subject of research for several decades in the case of influenza. However, so far there is only one live vaccine - Flumist - which is administered as a nasal spray. However, developing a live vaccine is a complicated and time consuming business. These vaccines are in development for SARS-CoV-2, but I don't expect them to be ready for the market anytime soon. "

“I currently see the relaxation of the measures and a return of rights to vaccinated people as premature. It is problematic when few people have had the chance to get vaccinated at all. In the long run there will be no avoiding loosening the drastic measures for vaccinated people. "

Prof. Dr. Verina Wild

Holder of the professorship for ethics in medicine, University of Augsburg

"The current vaccination prioritization aims to reduce the number of deaths and serious illnesses, and people who are in particularly close contact with COVID-19 patients are also to be protected. The Standing Vaccination Commission (STIKO) has also based its prioritization on preventing transmission. Overall, the prioritization is intended to prevent further damage from the pandemic as specifically as possible, and this strategy is very plausible. It also includes, for example, the option of giving priority to vaccinating teachers with high-risk diseases. The desire to deviate from the prioritization is understandable - and there are many groups that urge to be prioritized as well. It is also right that teachers, educators and other special groups should be vaccinated quickly. However, it should rather happen through massively increased efforts overall to improve the number and implementation of vaccinations. And as long as the restrictive measures cannot be lifted, greater efforts must be made to mitigate consequential damage - especially for children and the socially disadvantaged. "

“There is good evidence that vaccinations also help prevent or at least reduce the transmission of the virus from vaccinated people to others. This is very good news. However, it is not yet known how long this effect will last, whether it occurs with all vaccines or whether it is equally strong in all people. In addition, not everyone who wants to be vaccinated can still be vaccinated. For this reason alone, giving vaccinated people more freedom is currently not justifiable. If, at this point in time, certain groups are given priority vaccination, then all other groups are left behind for the time being. A preference for the vaccinated by currently still special freedoms would therefore be unfair to those who have not yet been able to receive a vaccination offer. But if everyone could be offered a vaccine with a vaccine that safely prevents transmission, those who accept it should be able to exercise all of their fundamental freedoms again. Those who, for good reasons, cannot be vaccinated should also be able to. However, those who do not want to be vaccinated and cannot provide good reasons for doing so (with a proven safe and effective vaccination) may have to accept certain restrictions on freedom. A vaccination that also prevents transmission is not only done to protect yourself, but also to help prevent further outbreaks for the benefit of everyone. This difficult ethical consideration also depends on how the properties of the virus and the disease develop.In any case, the goal should remain to achieve broad vaccination successes through an effective, fair, well organized and well communicated vaccination strategy so that everyone can lead a normalized life again. "

Information on possible conflicts of interest

Prof. Dr. Frank Dietrich: "There are no conflicts of interest."

All other: No information received.

References cited by the SMC

[I] Weekes M et al. (2021): Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection. Authorea. DOI: 10.22541 / au.161420511.12987747 / v1.

This is a peer-reviewed study that has not yet been scientifically appraised and should therefore be treated with caution.

[II] Hall VJ et al. (2021): Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study). Preprints with The Lancet. DOI: 10.2139 / ssrn.3790399.

This is a not yet scientifically appraised (peer-reviewed) study and should therefore be treated with caution.

[III] Dagan N et al. (2021): BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. NEJM. DOI: 10.1056 / NEJMoa2101765.

[IV] Voysey M et al. (2021): Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomized trials. The Lancet. DOI: 10.1016 / S0140-6736 (21) 00432-3.

[V] Isho B et al. (2020): Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients. medRxiv.

This is a not yet scientifically appraised (peer-reviewed) study and should therefore be treated with caution.

[VI] Gallo O et al. (2020): The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunology. 10.1038 / s41385-020-00359-2.

[VII] Russel MW et al. (2020): Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Frontiers in Immunology. DOI: 10.3389 / fimmu.2020.611337.