Characterization of SARS-CoV-2 genetic structure and infection clusters in a large German city based on integrated genomic surveillance, outbreak analysis, and contact tracing

Abstract

Viral genome sequencing can address key questions about SARS-CoV-2 evolution and viral transmission. Here, we present an integrated system of genomic surveillance in the German city of Düsseldorf, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) analysis of hospital outbreaks, d) integration of public health authority contact tracing data, and e) a user-friendly dashboard application as a central data analysis platform. The generated surveillance sequencing data (n = 320 SARS-CoV-2 genomes) showed that the development of the local viral population structure from August to December 2020 was consistent with European trends, with the notable absence of SARS-CoV-2 variants 20I/501Y.V1/B.1.1.7 and B.1.351 until the end of the local sampling period. Against a background of local surveillance and other publicly available SARS-CoV-2 data, four putative SARS-CoV-2 outbreaks at Düsseldorf University Hospital between October and December 2020 (n = 44 viral genomes) were investigated and confirmed as clonal, contributing to the development of improved infection control and prevention measures. An analysis of the generated surveillance sequencing data with respect to infection clusters in the population based on a greedy clustering algorithm identified five candidate clusters, all of which were subsequently confirmed by the integration of public health authority contact tracing data and shown to be represent transmission settings of particular relevance (schools, care homes). A joint analysis of outbreak and surveillance data identified a potential transmission of an outbreak strain from the local population into the hospital and back; and an in-depth analysis of one population infection cluster combining genetic with contact tracing data enabled the identification of a previously unrecognized population transmission chain involving a martial arts gym. Based on these results and a real-time sequencing experiment in which we demonstrated the feasibility of achieving sample-to-turnaround times of <30 hours with the Oxford Nanopore technology, we discuss the potential benefits of routine ultra-fast sequencing of all detected infections for contact tracing, infection cluster detection, and, ultimately, improved management of the SARS-CoV-2 pandemic.

SARS-CoV-2 Infection in Fully Vaccinated Individuals of Old Age Strongly Boosts the Humoral Immune Response

“… Phylogenetic tree of the outbreak sequences with local SASR-CoV2 isolates. Whole SARS-CoV-2 genome sequences from the outbreak were aligned with 506 local SARS-CoV-2 isolates sampled during the same week [provided by Walker et al ( 22 )] and a phylogenetic tree was calculated by the Neighbour-Joining method using the Tamura-Nei genetic distance model utilising the software Geneious R.10.2.6 and visualized with iTOL6.3 ( 23 ). The outbreak samples are highlighted in red.…”

“…This substitution has also not been associated with immune escape in the context of known variants of concern. In publicly available databases, this substitution has been described only in single isolates and is not present in 4095 isolates sequenced from regional infections ( 22 ). Although experimental confirmation is pending, we do not propose that the Q779K substitution promoted the outbreak after full vaccination.…”

SARS-CoV-2 infection in fully vaccinated individuals of old age strongly boosters the humoral immune response

“…Whole SARS-CoV-2 genome sequences from the outbreak were aligned with 506 local SARS-CoV-2 isolates sampled during the same week (provided by (Walker, Houwaart et al 2021)) and a phylogenetic tree was calculated by the Neighbor-Joining method using the Tamura-Nei genetic distance model utilizing the software Geneious R.10.2.6 and visulized with iTOL6.3 (Letunic and Bork 2016). The outbreak samples are highlighted in red.…”

“…This substitution has also not been associated with immune escape in the context of known variants of concern. In publicly available databases, this substitution has been described only in single isolates and is not present in 4095 isolates sequenced from regional infections (Walker, Houwaart et al 2021). Although experimental confirmation is pending, we do not propose that the Q779K substitution promoted the outbreak after full vaccination.…”

Integrated Genomic Surveillance reveals extensive onward transmission of travel-imported SARS-CoV-2 infections in the community

“…The system of Integrated Genomic Surveillance (IGS) in the city of Düsseldorf has been described elsewhere 3 . Briefly, the system involves rapid sequencing of a large proportion of local SARS-CoV-2 cases at the Centre for Medical Microbiology, Hospital Hygiene, and Virology of Heinrich Heine University Düsseldorf and an integration of genetic data with intensified backward contact tracing and structured case interviews at Düsseldorf Health Authority for the improved characterization of population transmission chains.…”