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bioRxiv2025

Characterizing Co-Circulating Respiratory Virus Genomic Diversity in Switzerland with Hybrid-Capture Sequencing and Phylogenetic Reconstructions: Insights into the 2023/24 Season

Respiratory viruses circulate yearly with strain-specific patterns. Although SARS-CoV-2 and Influenza A/B genomic surveillance is well-developed, most respiratory viruses are unevenly monitored, lacking geographical diversity to capture wider population dynamics. Consequently, insights into respiratory virus evolution are limited. We investigated the genetic diversity of these viruses within one country. During the 2023/24 season, we conducted whole-genome sequencing of 1129 clinical samples using a hybrid-capture protocol. These samples were pre-tested by real-time PCR panels throughout Switzerland. Leveraging publicly-available full-length genomes, we constructed background datasets representative of geographical diversity and built phylogenies for all viruses with more than 40 new high-quality genomes from this study. We detected 981 viruses and recovered 461 high-quality genomes, including 18 co-infections, from 437 PCR-positive and 6 PCR-negative samples. All viruses detected by PCR were also detected by sequencing in 56% of samples. The four most prevalent viruses were Influenza A/H1N1, SARS-CoV-2, RSV-A, and HPIV-3, and their seasonal spread was consistent with wastewater monitoring and influenza-like illness reports. Swiss viral genomes were representative of the global genomic diversity, with evidence for multiple introductions into Switzerland, and we identified putative Swiss clusters. In this proof-of-concept study, we focus on 3 viruses (Influenza A/H1N1, RSV-A/B, and HPIV-3), and we demonstrate the streamlined implementation of a broad respiratory virus genomic surveillance workflow with an off-the-shelf protocol and publicly-available software. In addition, we highlight additional evolutionary insights that can only be derived from genomic surveillance. Going forward, this dataset will be a useful resource for future investigations into respiratory viral genomic diversity.

genetics↗

bioRxiv2020

Within-patient genetic diversity of SARS-CoV-2

SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, is evolving into different genetic variants by accumulating mutations as it spreads globally. In addition to this diversity of consensus genomes across patients, RNA viruses can also display genetic diversity within individual hosts, and co-existing viral variants may affect disease progression and the success of medical interventions. To systematically examine the intra-patient genetic diversity of SARS-CoV-2, we processed a large cohort of 3939 publicly-available deeply sequenced genomes with specialised bioinformatics software, along with 749 recently sequenced samples from Switzerland. We found that the distribution of diversity across patients and across genomic loci is very unbalanced with a minority of hosts and positions accounting for much of the diversity. For example, the D614G variant in the Spike gene, which is present in the consensus sequences of 67.4% of patients, is also highly diverse within hosts, with 29.7% of the public cohort being affected by this coexistence and exhibiting different variants. We also investigated the impact of several technical and epidemiological parameters on genetic heterogeneity and found that age, which is known to be correlated with poor disease outcomes, is a significant predictor of viral genetic diversity. Author SummarySince it arose in late 2019, the new coronavirus (SARS-CoV-2) behind the COVID-19 pandemic has mutated and evolved during its global spread. Individual patients may host different versions, or variants, of the virus, hallmarked by different mutations. We examine the diversity of genetic variants coexisting within patients across a cohort of 3939 publicly accessible samples and 749 recently sequenced samples from Switzerland. We find that a small number of patients carry most of the diversity, and that patients with more diversity tend to be older. We also find that most of the diversity is concentrated in certain regions and positions of the virus genome. In particular, we find that a variant reported to increase infectivity is among the most diverse positions. Our study provides a large-scale survey of within-patient diversity of the SARS-CoV-2 genome.

genomics↗