LAPIS is a fast web API for massive open virus sequencing data.

BACKGROUND: Recent epidemic outbreaks such as the SARS-CoV-2 pandemic and the mpox outbreak in 2022 have demonstrated the value of genomic sequencing data for tracking the origin and spread of pathogens. Laboratories around the globe generated new sequences at unprecedented speed and volume and bioinformaticians developed new tools and dashboards to analyze this wealth of data. However, a major challenge that remains is the lack of simple and efficient approaches for accessing and processing sequencing data. RESULTS: The Lightweight API for Sequences (LAPIS) facilitates rapid retrieval and analysis of genomic sequencing data through a REST API. It supports complex mutation- and metadata-based queries and can perform aggregation operations on massive datasets. LAPIS is optimized for typical questions relevant to genomic epidemiology. Using a newly-developed in-memory database engine, it has a high speed and throughput: between 25 January and 4 February 2023, the SARS-CoV-2 instance of LAPIS, which contains 14.5 million sequences, processed over 20 million requests with a mean response time of 411 ms and a median response time of 1 ms. LAPIS is the core engine behind our dashboards on genspectrum.org and we currently maintain public LAPIS instances for SARS-CoV-2 and mpox. CONCLUSIONS: Powered by an optimized database engine and available through a web API, LAPIS enhances the accessibility of genomic sequencing data. It is designed to serve as a common backend for dashboards and analyses with the potential to be integrated into common database platforms such as GenBank.

Rapid escape of new SARS-CoV-2 Omicron variants from BA.2 directed antibody responses

In November 2021 Omicron BA.1, containing a raft of new spike mutations emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or SARS-CoV-2 infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional RBD amino-acid substitutions compared to BA.2. We describe a panel of 25 potent mAbs generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titre of vaccine or BA.1, BA.2 or BA.4/5 immune serum. Graphical Dijokaite-Guraliuc et al. analyse potently neutralizing antibodies from vaccinated individuals with BA.2 breakthrough infections. The antibodies bind 3 sites on the receptor binding domain, 2 in common with early pandemic antibodies. Mutations in more recent variants map closely to these sites leading to reduced neutralization in all but one mAb.

Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.

CoV-Spectrum: Analysis of Globally Shared SARS-CoV-2 Data to Identify and Characterize New Variants.

SUMMARY: The CoV-Spectrum website supports the identification of new SARS-CoV-2 variants of concern and the tracking of known variants. Its flexible amino acid and nucleotide mutation search allows querying of variants before they are designated by a lineage nomenclature system. The platform brings together SARS-CoV-2 data from different sources and applies analyses. Results include the proportion of different variants over time, their demographic and geographic distributions, common mutations, hospitalization and mortality probabilities, estimates for transmission fitness advantage and insights obtained from wastewater samples. AVAILABILITY AND IMPLEMENTATION: CoV-Spectrum is available at https://cov-spectrum.ethz.ch. The code is released under the GPL-3.0 license at https://github.com/cevo-public/cov-spectrum-website.

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa.

Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa's fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69-70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08-0.09) and 0.10 (95% CI: 0.09-0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.