Statement of Society of Virology (GfV) on the introduction of COVID-19 vaccinations

Efforts to develop a vaccine against COVID-19 are running at highest intensity worldwide. The large number of vaccine candidates currently under investigation [1], the initial results from animal studies [2] and immune responses in human clinical trials [3-6] have considerably increased the probability that preliminary proof of tolerability and efficacy for one or more vaccines will be achieved in the foreseeable future. As part of the licensing process, an independent authority can then examine the efficacy and safety and, if necessary, determine the suitability of the vaccines in principle.

One of the most important societal questions that needs to be answered after the first COVID-19 vaccines are licensed for Germany is who should be offered vaccination first (prioritisation). It can be assumed that the demand for vaccine doses will exceed the supply, at least in the first few months. The primary goal in introducing vaccination must be to reduce COVID19-related deaths and severe clinical illness. To achieve this with a limited number of available vaccine doses, the prioritisation of specific groups of people or occupations must take into account multiple aspects of the epidemiology of the SARS-CoV-2 pandemic, the efficacy and mode of action of the vaccines in different age and risk groups, and the practicality of administering the vaccinations. In Germany, the Standing Committee on Vaccination (STIKO) has the legal mandate to make recommendations based on vaccine approval. The procedure by which the STIKO will implement the evidence-based benefit-risk assessment for COVID-19 vaccination and also consider ethical aspects in its prioritisation recommendation is described in a recently published statement [7]. Furthermore, in the national pandemic plan [8], there are four prioritisation groups to be defined for SARS-CoV-2:

1. people who particularly benefit from vaccination (e.g. older population groups)
2. people who have frequent contact with particularly vulnerable people (e.g. medical staff in care facilities and hospitals)
3. people who have a particularly strong influence on virus circulation (e.g. age groups with particularly high infection rates such as the 20-39 year olds [9])
4. people who are required to maintain public safety or the state infrastructure

In the following, we highlight important virological aspects that should be considered in prioritisation.

The goal of vaccination from the individual's perspective is to protect against the disease caused by a pathogen. Ideally, the vaccine induces immunity that completely prevents infection with the pathogen and interrupts the chain of transmission. However, protection against disease can also be achieved by reducing, but not completely preventing, the spread of the virus in the vaccinated person. In this case, transmission is less likely, but not completely stopped. Since a large number of different vaccine classes are currently being tested for tolerability and efficacy, and the mode of action can differ from vaccine to vaccine, a differentiated approach is necessary. Depending on the route by which future COVID-19 vaccines lead to protection, their optimal areas of application could also differ. Preferential vaccination of groups of people who have a particularly large impact on virus circulation only makes sense if the vaccination efficiently prevents further spread and does not merely reduce the severity of the infection. In the current pandemic, it is also difficult to define this group of people, since a considerable part of the infections could be due to "superspreaders" who cannot be identified in advance. A recent but not yet scientifically peer-reviewed computer modelling of the maximum benefit of limited availability of COVID-19 vaccines concludes that such prioritisation is only beneficial if sufficient doses of a very effective vaccine are available to vaccinate a large proportion of the relevant groups of people [10]. Under all other modelling assumptions, direct vaccination of the vulnerable groups of people was of greater benefit [10].

In the case of SARS-CoV-2 infection, old age is the most frequent and probably the most important risk factor known to date for an intensive or fatal course of the disease [11]. However, other diseases in all age groups can also increase the risk of severe courses. It is therefore important to examine the safety and efficacy of vaccines, especially in older people and other risk groups. If the effectiveness of vaccination in risk groups is low (e.g. the very elderly), it may be more efficient to vaccinate close contacts, such as caregivers or nursing staff, instead of the particularly at-risk groups, so that they are eliminated as carriers of the disease. Here, too, the prerequisite is that the vaccination prevents the SARS-CoV-2 infection and not only the symptoms of the disease. Medical staff in care facilities and hospitals are particularly eligible for vaccination as part of such a cocoon strategy.

Vaccination of medical staff may also be necessary to maintain medical care structures. Experience from northern Italy and New York demonstrates overloading of care structures when infection rates are high, which is further exacerbated by COVID-19 illnesses among staff. However, a threat to public safety or state infrastructure outside the health care system seems unlikely, as the percentage of people simultaneously infected with COVID-19 is low due to the mostly mild course in the age group of professionals.

The rate of new SARS-CoV-2 infections varies considerably from state to state and also within states by region. The best possible benefit for society as a whole could therefore possibly be achieved if vaccine distribution also took regional case numbers into account. However, it is likely to be very difficult to implement such an approach to prioritisation politically.

Administering millions of vaccine doses within a short period of time according to prioritisation criteria that have yet to be defined is also a logistical challenge. Depending on the type of vaccine approved, cold chains may be required or only serial vaccinations may be possible, as bottlenecks in filling would mean that the vaccines could only be provided in containers of 50 or 100 doses.

However, the high speed of vaccine development involves a number of risks, which the GfV has already pointed out together with the German Society for Immunology (https://www.g-f-v.org/node/1285). Despite the greatest possible care, rapid and widespread use of a vaccine increases the risk that rare side effects occurring late after vaccination will initially go undetected. Since most vaccine-associated side effects occur within the first few weeks after vaccination [12], a risk-benefit assessment may justify rapid widespread use. In this case, however, there is an urgent need to monitor the efficacy and safety of COVID-19 vaccination in prospective studies at the same time as its introduction.

Even though the present statement highlights many open questions and difficulties, vaccination remains the most promising approach to drastically reduce the number of severe courses of the disease and deaths and, depending on the effectiveness of the vaccine, also to reduce the spread of the virus. This will enable a life with fewer COVID-19-related limitations in the medium term.

Conclusion: Based on the study results available so far, the development of COVID-19 vaccines seems promising. Therefore, despite many uncertainties, it is important to prepare for their introduction at all levels. This must include education on the efficacy and safety of COVID-19 vaccines as well as transparent and generally accepted decision-making on the preferential vaccination of certain population groups. Since only short follow-up periods are available for the vaccines, the introduction of vaccination must be continuously accompanied by scientific studies on the efficacy and safety of the vaccines.

Read as PDF

The Board of Directors of the Society of Virology

Authors (in alphabetical order):

Prof. Dr Ralf Bartenschlager, Molecular Virology, Heidelberg University Hospital

Prof. Dr Ulf Dittmer, Institute for Virology, University Hospital Essen

Prof. Dr Isabella Eckerle, Centre for Emerging Viral Diseases, University Hospital Geneva, Switzerland

Prof. Dr. Hartmut Hengel, Institute of Virology, University Hospital Freiburg

Prof. Dr. Heidemarie Holzmann, Centre for Virology, Medical University of Vienna, Austria

Prof. Dr. Thomas Mertens, Institute for Virology, University Hospital Ulm

Prof. Dr Stephanie Pfänder, Department of Molecular and Medical Virology, Ruhr-Universität Bochum

Prof. Dr Hendrik Streeck, Institute for Virology, University Hospital Bonn

Prof. Dr. Matthias Tenbusch, Virological Institute, Clinical and Molecular Virology, University Hospital Erlangen

Prof. Dr. Klaus Überla, Virological Institute, Clinical and Molecular Virology, University Hospital Erlangen

Sources

1] Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20: 615-632. doi:10.1038/s41577-020-00434-6.

[2] Dagotto G, Yu J, Barouch DH. Approaches and Challenges in SARS-CoV-2 Vaccine Development. Cell Host and Microbe. Cell Press; 2020. pp. 364–370. doi:10.1016/j.chom.2020.08.002

[3] Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396: 467-478. doi:10.1016/S0140-6736(20)31604-4

[4] Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. 2020; 1-8. doi:10.1038/s41586-020-2639-4.

[5] Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020;395: 1845-1854. doi:10.1016/S0140-6736(20)31208-3

[6] Logunov DY, Dolzhikova I V, Zubkova O V, Tukhvatullin AI, Shcheblyakov D V, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396: 887-897. doi:10.1016/S0140-6736(20)31866-3

[7] Standing Commission on Vaccination (STIKO) at the Robert Koch Institute. Standing Commission on Vaccination: statement of the Standing Commission on Vaccination on future vaccination against COVID-19. Epidemiol Bull. 2020; 8-10. doi:10.25646/7090

[8] RKI. National Pandemic Plan Part II. doi:10.17886/rkipubl2016004.5

[9] RKI - Coronavirus SARS-CoV-2 - Situation report as of 7.9.2020.Available: https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsb...)

[10] Matrajt L, Eaton J, Leung T, Brown ER. Vaccine optimization for COVID-19, who to vaccinate first? medRxiv Prepr Serv Heal Sci. 2020; 2020.08.14.20175257. doi:10.1101/2020.08.14.20175257.

[11] Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020;369: m1985. doi:10.1136/bmj.m1985

[12] Weißer K, Barth I, Keller-Stanislawski B. Safety of vaccines. Bundesgesundheitsblatt - Gesundheitsforsch - Gesundheitsschutz. 2009;52: 1053-1064. doi:10.1007/s00103-009-0961-y