Updated statement of the GfV on the sequencing of SARS-CoV-2 in Germany

The rapid spread of new SARS-CoV-2 variants in England (B1.1.7 or variant of concern (VOC) 202012/01) and South Africa (B.1.351, also known as 501.V2 variant), which differ significantly from previously circulating variants in terms of their genome, raises the question of whether these variants are also widespread in Germany.

In variant B1.1.7, there are 8 mutations that lead to amino acid exchanges in the spike protein (S) of SARS-CoV-2, which possibly entail a change in the biological properties of S. One important amino acid exchange is found in the receptor binding motif[1] of S at position 501 (N501Y). This mutation, alone or in combination with other mutations, could lead to an increased binding ability to the human receptor ACE-2[2]. For another mutation, a deletion leading to the loss of amino acids at positions 69 and 70, an increase in the infectivity of the virus in cell cultures was shown in a previous publication[3].

Variant B.1.351, which was detected in South Africa, also contains 8 mutations that lead to amino acid exchanges in S of SARS-CoV-2. Two of these mutations are in the receptor binding motif (E484K and N501Y)[4]. Preliminary studies suggest that these mutations have very little effect on neutralisation by antibodies produced as a result of vaccination with an mRNA vaccine. However, these mutations appear to interfere with the binding of some antibodies being developed for therapy[5],[6].

The Coronavirus Consiliary Laboratory has currently analysed 1126 genome sequences of SARS-CoV-2 from all parts of Germany[7]. In the meantime, both variant B1.1.7 and variant B1.351 have been found. However, nothing can be said so far about the possible spread of these variants in Germany.

The sequencing of entire virus genomes and bioinformatic evaluation are time-consuming processes for which specific infrastructures are required, but which are not available everywhere. Therefore, current events are only inadequately recorded. An alternative is PCR methods for the targeted detection of the new SARS-CoV-2 variants, in order to be able to efficiently record the spread or spread of these variants by testing large numbers of samples. In addition, there are intensive efforts to improve the framework conditions for virus genome sequencing and thus molecular surveillance for SARS-CoV-2 in Germany.

According to a preliminary risk assessment by the European Centre for Disease Prevention and Control (ECDC), based on mathematical modelling[8], the new variant B1.1.7 may have a transmission rate up to 56% higher than previously circulating SARS-CoV-2 variants[9]. A study from the UK, which has not yet been peer-reviewed, also indicates a higher infection rate of SARS-CoV-2 variant B1.1.7[10]. However, this assessment must be verified in further studies. The GfV also points out that a more rapid spread of SARS-CoV-2 does not necessarily have to be accompanied by more severe courses of disease. However, it makes it clear once again that compliance with hygiene measures and contact reduction is urgently required. At the same time, the occurrence of virus variants shows that efforts for systematic molecular surveillance in Germany should be urgently intensified.

Mutations in SARS-CoV-2 can, in principle, have consequences for both vaccine efficacy and antibody therapy. A first study has shown that sera from 20 participants in the already published phase 3 study of the BioNTech/Pfizer vaccine BNT162b2 (Comirnaty) neutralised a SARS-CoV-2 virus with a mutation at position 501 (a key mutation of the B1.1.7 variant) to the same extent as the virus without this mutation. So far, there are only very preliminary studies on the possible effects of combinations of mutations as found in the above-mentioned variants. According to a publication that has not yet been peer-reviewed, the mutations in the B.1.351 variant from South Africa could clearly reduce the effectiveness of neutralising antibodies in the serum of people who have previously been infected with the original SARS-CoV-2[11]. This could mean that these individuals are at risk for re-infection with the South African variant. In addition, this study provides preliminary evidence that these mutations reduce the efficacy of therapeutic S-specific antibodies, sometimes significantly. However, these observations need to be assessed as preliminary and confirmed in further studies. They do, however, make the dynamics of SARS-CoV-2 and thus the need for rapid control of the pandemic very clear in order to minimise the risk of further variants emerging.

The Board of Directors of the Society of Virology

Prof. Dr. Ralf Bartenschlager, Heidelberg University Hospital

Prof. Dr. Thomas Stamminger, University Hospital Ulm

Prof. Dr. Ulf Dittmer, University Hospital Essen

Prof. Dr. Sandra Ciesek, University Hospital Frankfurt

Prof. Dr. Klaus Überla, Erlangen University Hospital

with the participation of:

Prof. Dr. Hartmut Hengel, University Hospital Freiburg

Sources

[1] Area where the SARS-CoV-2 binds to its human receptor ACE-2

[2] Zahradník et al: 2021: doi: https://doi.org/10.1101/2021.01.06.425392

[3] Kemp et al, 2021: doi: https://doi.org/10.1101/2020.12.14.422555

[4] Tegally et al, 2020: doi: https://doi.org/10.1101/2020.12.21.20248640

[5] Starr et al, 2020: https://www.biorxiv.org/content/10.1101/2020.11.30.405472v1

[6] Wang et al, 2021: doi: https://doi.org/10.1101/2021.01.15.426911

[7] https://civnb.info/sequences/ (as of 19.01.2021)

[8] https://cmmid.github.io/topics/covid19/uk-novel-variant.html

[9] Risk related to spread of new SARS-CoV-2 variants of concern in the EU/EEA; 29.12.2020; page 11

[10] Walker et al, 2021: doi: https://doi.org/10.1101/2021.01.13.21249721

[11] Wibmer et al, 2021: doi: https://doi.org/10.1101/2021.01.18.427166