Marc Niebel

Background: Robust methods to track pathogens support public health surveillance. Both wastewater (WW) and individual whole genome sequencing (WGS) are used to assess viral variant diversity and spread. However, their relative performance and the information provided by each approach have not been sufficiently quantified. Therefore, we conducted a comparative evaluation using extensive individual and wastewater longitudinal SARS-CoV-2 WGS datasets in Northern Ireland (NI). Methods: WGS of SARS-CoV-2 was performed on >4k WW samples and >23k individuals across NI from 14 ^th November 2021 to 11 ^th March 2023. SARS-CoV-2 RNA was amplified using the ARTIC nCov-2019 protocol and sequenced on an Illumina MiSeq. Wastewater data were analysed using Freyja to determine variant compositions, which were compared to individual data through time series and correlation analyses. Inter-programme agreements were evaluated by mean absolute error (MAE) calculations. WW treatment plant (WWTP) performances were ranked by mean MAE. Volatile periods were identified using numerical derivative analyses. Geospatial spreading patterns were determined by horizontal curve shifting. Findings: Strong concordance was observed between wastewater and individual variant compositions and distributions, influenced by sequencing rate and variant diversity. Overall variant compositions derived from individual sequences and each WWTP were regionally clustered rather than dominated by local population size. Both individual and WW sequencing detected common nucleotide substitutions across many variants and complementary additional substitutions. Conserved spreading patterns were identified using both approaches. Interpretation: Both individual and wastewater WGS effectively monitor SARS-CoV-2 variant dynamics. Combining these approaches enhances confidence in predicting the composition and spread of major variants, particularly with higher sequencing rates. Each method detects unique mutations, and their integration improves overall genome surveillance. Funding: Individual sequencing was funded via the Belfast Health and Social Care Trust (Department of Health for Northern Ireland) and the COVID-19 Genomics UK (COG-UK) consortium, which was supported by the Medical Research Council (MRC), UK Research and Innovation (UKRI), the National Institute for Health Research (NIHR), the Department of Health and Social Care (DHSC), and the Wellcome Sanger Institute. The NI Wastewater Surveillance Programme was funded by the Department of Health for Northern Ireland. EPT was supported through the COG-UK Early Career Funding Scheme.

Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.