Andreas Walker

BACKGROUND: Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. METHODS: In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. RESULTS: Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. CONCLUSIONS: Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population.

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.

Oncology patients receiving cytostatic therapy used to be at high risk of HBV infection when HBV screening measures were less reliable. Infections acquired under these conditions often persist, like those acquired perinatally or during early infancy. We studied the long-term clinical outcomes, viral characteristics, and virus-specific T-cell immunity of chronic HBV infection acquired during chemotherapy. We examined 16 chronically HBV-infected former paediatric oncology patients who were infected during cytostatic treatment in the 1980s. Patients underwent physical examination, laboratory liver function testing, non-invasive measurement of liver stiffness, and determination of HBV serology and DNA levels. If the material was sufficient, HBV sub-genotype, drug resistance and immune escape mutations, and mutations associated with HBeAg negativity were analysed. The frequency of HBV core-specific CD8+ T cells was measured after in vitro antigen-specific expansion. All but one patient were chronically infected with detectable HBsAg but were HBeAg-negative, mostly with low viraemia. Four patients were under ongoing effective antiviral therapy, and four required treatment initiation due to high viraemia or advanced liver disease. Hepatic effects were predominantly observed in highly viraemic patients. No drug resistance or immune escape mutations were observed. In two highly viraemic patients, basal core promoter and precore region mutations reducing HBeAg expression were identified. HBV core-specific CD8+ T cells were detected in all patients, but their frequency was low. In conclusion, more than 30 years after primary HBV infection was acquired during chemotherapy, the course of infection still resembles that of perinatally acquired infections.

Abstract Understanding pathogen transmission is key to effective infection prevention. From February to December 2021, we implemented genomics-enhanced contact tracing for SARS-CoV-2 in Düsseldorf, Germany, integrating data on 32,380 cases, 49,906 contact tracing records, 162 outbreaks, and 8,028 viral genomes (sequencing coverage 24.5%). Combining epidemiological and genetic data, we found a putative infection source for 19% of sequenced and 44% of all cases. Household-associated transmission accounted for up to 40% of all cases; classical contact tracing had limited sensitivity for non-household contacts, and gastronomy, hospital, school and kindergarten contexts were genetically found to be likely enriched for undetected transmissions. Outbreaks were associated with 8% of cases; school, kindergarten and nightlife outbreaks were strongly connected to the community, with nightlife outbreaks showing a strong post-outbreak increase in genetically associated cases. Sequencing detected previously unrecognized links between school outbreaks and 18% additional outbreak-associated sequenced cases. In conclusion, in addition to classical contact tracing, SARS-CoV-2 sequencing was required to achieve an improved resolution of transmission dynamics; future implementations of genomics-enhanced contact tracing should aim for sequencing rates of at least 15% to enable effective characterization of infection contexts and outbreaks.

Abstract Integration of genomic surveillance with contact tracing provides a powerful tool for the reconstruction of person-to-person pathogen transmission chains. We report two large clusters of SARS-CoV-2 cases (“Delta” clade, 110 cases combined) detected in July 2021 by Integrated Genomic Surveillance in Düsseldorf. Structured interviews and deep contact tracing demonstrated an association to a single SARS-CoV-2 infected return traveller (Cluster 1) and to return travel from Catalonia and other European countries (Cluster 2), highlighting the importance of containing travel-imported SARS-CoV-2 infections.