Statement of Society of Virology on SARS-CoV-2 "Variants of Concern" and the need for the second vaccination dose for protection against disease

SARS-CoV-2 is a virus with an RNA genome. What these so-called RNA viruses have in common is that when they copy their genetic material, they do not copy it exactly but make mistakes. These errors lead to mutations and the corresponding virus is a variant. If these variants have an advantage, such as better transmissibility or reduced attackability by the immune system, they prevail over the viruses currently circulating in the population and displace them. This natural process of the emergence of virus variants and their selection leads to constant changes in the composition of the prevailing virus population. This characteristic is also found in other RNA viruses, although the extent of genetic change varies greatly. For example, the diversity of SARS-CoV-2 is lower than that of influenza viruses[1], which is why the vaccine for the latter must be adapted annually to the prevailing virus variants. The lower genetic diversity in coronaviruses is partly due to the fact that coronaviruses have a correction mechanism that checks and, if necessary, corrects the quality of the genome copies during replication, a property that most RNA viruses do not possess.

The mutations can arise at any point in the genome and are therefore distributed throughout the entire genome of SARS-CoV-2. Most mutations are neutral or even detrimental to the virus[2], but some can alter the biological properties of the virus. In this context, the mutations affecting the SARS-CoV-2 surface protein (the spike protein) are particularly noteworthy. These mutations can influence the properties of the virus in many ways. They can a) change the transmissibility, b) have an impact on the course of the disease, c) change the controllability by the immune response and thus d) influence the effectiveness of the vaccination response.

The Robert Koch Institute currently lists four so-called variants of concern (VOC): Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2)[3]. These variants of concern have several alterations in the spike protein that may be associated with particular properties such as higher transmissibility and altered responsiveness to the immune response.

A first change to the original virus already occurred at the beginning of the pandemic. This resulted in a mutation in the spike protein (D614G), which represents a very early adaptation of the virus to humans as hosts and entails better transmissibility than the virus of origin[4],[5],[6]. The first VOC in Germany was Alpha, which became the predominant variant in January 2021 and within a few weeks displaced the virus that had been predominant until then[7]. In addition to the alpha variant, the beta and gamma variants were also detected around the same time, which, in contrast to the alpha variant, show mutations in the spike protein that not only have an impact on transmissibility but also on the response to the immune response to the virus. Interestingly, the beta and gamma variants have three mutations (positions 417, 484 and 501 in the spike protein) that arose independently at different locations. This is an indication that these changes are of great advantage for virus spread.

With the Delta variant, which was first detected in India, an even more infectious variant has now emerged compared to Alpha, which, according to initial indications from Great Britain, also has a hospitalisation rate that is about two times higher[8]. The latest report from Public Health England, dated 18 June 2021, shows that the "crude case fatality rate" for VOC Delta is currently lower than for all other variants[9]. However, it is noted that there is not yet enough data to make a formal assessment of the fatality rate of Delta, weighted by age, compared to other variants. Variant Delta has displaced variant Alpha in India[10]. A similar displacement of alpha by delta can be observed in the UK at the moment[11],[12].

The current report of the Robert Koch Institute[13] of 16 June 2021 also shows an increase in the share of the delta variant among the viruses examined for Germany and a decrease in the share of the alpha variant with overall decreasing infection figures. With a view to the UK, for example, it is very likely that the currently dominant alpha variant will also be displaced by delta in Germany. The time frame in which this could take place is difficult to predict and depends, among other things, on the further development of incidences, the vaccination rate and the registration of the delta variant in the coming travel period to Germany.

In this context, the Society of Virology would like to point out the importance of the second vaccination for protection against COVID-19 disease. First data from Great Britain show how essential the second dose of vaccination is for protection against disease with the VOC Delta[14],[15]. With the Delta variant, protection against disease after the first dose of vaccination is only present in ~33% of cases with the BioNTech/ Pfizer and AstraZeneca vaccines. Only after the second dose is a high level of immune protection achieved with both vaccines, and this is then comparable to the effectiveness against infection with VOC alpha. For the single vaccination with the vaccine from Johnson & Johnson, there are currently no data on the effectiveness of the vaccine against Delta.

The importance of the second vaccination dose is also explained, among other things, by experiments in cell culture. These show that the neutralising antibodies against VOC Delta, which are important for the immune defence against SARS-CoV-2, can only be detected after the second vaccination dose[16]. This can be explained by the observation that VOC Delta is altered in the surface protein in such a way that the antibodies are less able to bind and are therefore less able to prevent VOC Delta from infecting cells. One therefore needs the second vaccination dose to induce the formation of a critical amount of neutralising antibodies.

The Board of Directors of the Society of Virology

Prof. Dr. Ralf Bartenschlager, Universitätsklinikum Heidelberg

Prof. Dr. Thomas Stamminger, Universitätsklinikum Ulm

Prof. Dr. Ulf Dittmer, Universitätsklinikum Essen

Prof. Dr. Sandra Ciesek, Universitätsklinikum Frankfurt

Prof. Dr. Klaus Überla, Erlangen University Hospital

Sources

[1] Rausch et al., PNAS 2020 117 (40) 24614-24616

[2] Van Drop et al., Infect Genet Evol. 2020 83: 104351

[3] Report on viral variants of SARS-CoV-2 in Germany; 16 June 2021

[4] Zhou et al., Nature 2021 (592) 122–127

[5] Hou et al., Science 2020 370 (6523) 1464–1468

[6] Korber et al., Cell 2020 182 (4) 812-827.e19

[7] Report on viral variants of SARS-CoV-2 in Germany; 16 June 2021.

[8] SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 15

[9] SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 16

[10] ECDC – Threat Assessment Brief: Emergence of SARS-CoV-2 B.1.617 variants in India and situation in the EU/EEA; 11.05.2021

[11] Sheihk et al, Lancet 2021 http://dx.doi.org/10.1016/S0140-6736(21)01358-1.

[12] SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 15

[13] Report on viral variants of SARS-CoV-2 in Germany; 16 June 2021.

[14] Bernal et al., 2021: https://doi.org/10.1101/2021.05.22.21257658

[15] SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 15

[16] Wall et al, The Lancet 2021 39 (10292), 2331-2333.