Advancing Precision Vaccinology by Molecular and Genomic Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 in Germany, 2021.

BACKGROUND: Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern led to an expansion of genomic sequencing activities in Germany. METHODS: At Robert Koch Institute (RKI), the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance at the national scale, SARS-CoV-2-positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI. RESULTS: We report analyses of 3623 SARS-CoV-2 genomes collected between December 2020 and December 2021, of which 3282 were randomly sampled. All variants of concern were identified in the sequenced sample set, at ratios equivalent to those in the 100-fold larger German GISAID sequence dataset from the same time period. Phylogenetic analysis confirmed variant assignments. Multiple mutations of concern emerged during the observation period. To model vaccine effectiveness in vitro, we employed authentic-virus neutralization assays, confirming that both the Beta and Zeta variants are capable of immune evasion. The IMS-SC2 sequence dataset facilitated an estimate of the SARS-CoV-2 incidence based on genetic evolution rates. Together with modeled vaccine efficacies, Delta-specific incidence estimation indicated that the German vaccination campaign contributed substantially to a deceleration of the nascent German Delta wave. CONCLUSIONS: SARS-CoV-2 molecular and genomic surveillance may inform public health policies including vaccination strategies and enable a proactive approach to controlling coronavirus disease 2019 spread as the virus evolves.

CovRadar: continuously tracking and filtering SARS-CoV-2 mutations for genomic surveillance.

SUMMARY: The ongoing pandemic caused by SARS-CoV-2 emphasizes the importance of genomic surveillance to understand the evolution of the virus, to monitor the viral population, and plan epidemiological responses. Detailed analysis, easy visualization and intuitive filtering of the latest viral sequences are powerful for this purpose. We present CovRadar, a tool for genomic surveillance of the SARS-CoV-2 Spike protein. CovRadar consists of an analytical pipeline and a web application that enable the analysis and visualization of hundreds of thousand sequences. First, CovRadar extracts the regions of interest using local alignment, then builds a multiple sequence alignment, infers variants and consensus and finally presents the results in an interactive app, making accessing and reporting simple, flexible and fast. AVAILABILITY AND IMPLEMENTATION: CovRadar is freely accessible at https://covradar.net, its open-source code is available at https://gitlab.com/dacs-hpi/covradar. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Rise and Fall of SARS-CoV-2 Lineage A.27 in Germany.

Here, we report on the increasing frequency of the SARS-CoV-2 lineage A.27 in Germany during the first months of 2021. Genomic surveillance identified 710 A.27 genomes in Germany as of 2 May 2021, with a vast majority identified in laboratories from a single German state (Baden-Wuerttemberg, n = 572; 80.5%). Baden-Wuerttemberg is located near the border with France, from where most A.27 sequences were entered into public databases until May 2021. The first appearance of this lineage based on sequencing in a laboratory in Baden-Wuerttemberg can be dated to early January '21. From then on, the relative abundance of A.27 increased until the end of February but has since declined-meanwhile, the abundance of B.1.1.7 increased in the region. The A.27 lineage shows a mutational pattern typical of VOIs/VOCs, including an accumulation of amino acid substitutions in the Spike glycoprotein. Among those, L18F, L452R and N501Y are located in the epitope regions of the N-terminal- (NTD) or receptor binding domain (RBD) and have been suggested to result in immune escape and higher transmissibility. In addition, A.27 does not show the D614G mutation typical for all VOIs/VOCs from the B lineage. Overall, A.27 should continue to be monitored nationally and internationally, even though the observed trend in Germany was initially displaced by B.1.1.7 (Alpha), while now B.1.617.2 (Delta) is on the rise.