Dreifuss David, Huisman Jana S, Rusch Johannes C, Caduff Lea, Ganesanandamoorthy Pravin, Devaux Alexander J, Gan Charles, Stadler Tanja, Kohn Tamar, Ort Christoph, Beerenwinkel Niko, Julian Timothy R
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Nat Commun. 2025 Aug 12;16(1):7456. doi: 10.1038/s41467-025-62790-y.
The COVID-19 pandemic has accelerated the development and adoption of wastewater-based epidemiology. Wastewater samples can provide genomic information for detecting and assessing the spread of SARS-CoV-2 variants in communities and for estimating important epidemiological parameters such as the selection advantage of a viral variant. However, despite demonstrated successes, epidemiological data derived from wastewater suffers from potential biases. Of particular concern are shedding profiles, which can affect the relationship between true viral incidence and viral loads in wastewater. Changes in shedding between variants may decouple the established relationship between wastewater loads and clinical test data. Using mathematical modeling, simulations, and Swiss surveillance data, we demonstrate that estimates of the selection advantage of a variant are not biased by shedding profiles. We show that they are robust to differences in shedding between variants under a wide range of assumptions, and identify specific conditions under which this robustness may break down. Additionally, we demonstrate that differences in shedding only briefly affect estimates of the effective reproduction number. Thus, estimates of selective advantage and reproduction numbers derived from wastewater maintain their advantages over traditional clinical data, even when there are differences in shedding among variants.
新冠疫情加速了基于废水的流行病学的发展与应用。废水样本能够提供基因组信息，用于检测和评估严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体在社区中的传播情况，并估算重要的流行病学参数，如病毒变体的选择优势。然而，尽管已取得显著成效，但源自废水的流行病学数据仍存在潜在偏差。尤其值得关注的是病毒排放模式，它可能会影响废水中真实病毒发病率与病毒载量之间的关系。变体之间病毒排放的变化可能会使废水载量与临床试验数据之间已确立的关系脱节。通过数学建模、模拟以及瑞士的监测数据，我们证明变体选择优势的估计不会因病毒排放模式而产生偏差。我们表明，在广泛的假设条件下，它们对于变体之间病毒排放在差异具有稳健性，并确定了这种稳健性可能失效的具体条件。此外，我们证明病毒排放的差异只会短暂影响有效繁殖数的估计。因此，即使变体之间存在病毒排放差异，源自废水的选择优势和繁殖数估计相对于传统临床数据仍保持其优势。
