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Abstract

Background

Throughout the COVID-19 pandemic, SARS-CoV-2 genetic variants of concern (VOCs) have repeatedly and independently arisen. VOCs are characterised by increased transmissibility, increased virulence or reduced neutralisation by antibodies obtained from prior infection or vaccination. Tracking the introduction and transmission of VOCs relies on sequencing, typically whole genome sequencing of clinical samples. Wastewater surveillance is increasingly used to track the introduction and spread of SARS-CoV-2 variants through sequencing approaches.

Aim

Here, we adapt and apply a rapid, high-throughput method for detection and quantification of the relative frequency of two deletions characteristic of the Alpha, Beta, and Gamma VOCs in wastewater.

Methods

We developed drop-off RT-dPCR assays and an associated statistical approach implemented in the R package WWdPCR to analyse temporal dynamics of SARS-CoV-2 signature mutations (spike Δ69–70 and ORF1a Δ3675–3677) in wastewater and quantify transmission fitness advantage of the Alpha VOC.

Results

Based on analysis of Zurich wastewater samples, the estimated transmission fitness advantage of SARS-CoV-2 Alpha based on the spike Δ69–70 was 0.34 (95% confidence interval (CI): 0.30–0.39) and based on ORF1a Δ3675–3677 was 0.53 (95% CI: 0.49–0.57), aligning with the transmission fitness advantage of Alpha estimated by clinical sample sequencing in the surrounding canton of 0.49 (95% CI: 0.38–0.61).

Conclusion

Digital PCR assays targeting signature mutations in wastewater offer near real-time monitoring of SARS-CoV-2 VOCs and potentially earlier detection and inference on transmission fitness advantage than clinical sequencing.

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/content/10.2807/1560-7917.ES.2022.27.10.2100806
2022-03-10
2024-04-28
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2022.27.10.2100806
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Inferring transmission fitness advantage of SARS-CoV-2 variants of concern from wastewater samples using digital PCR, Switzerland, December 2020 through March 2021
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Lea+Caduff&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Caduff Lea</a>, <a href="/search?value1=David+Dreifuss&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Dreifuss David</a>, <a href="/search?value1=Tobias+Schindler&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Schindler Tobias</a>, <a href="/search?value1=Alexander+J+Devaux&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Devaux Alexander J</a>, <a href="/search?value1=Pravin+Ganesanandamoorthy&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Ganesanandamoorthy Pravin</a>, <a href="/search?value1=Anina+Kull&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Kull Anina</a>, <a href="/search?value1=Elyse+Stachler&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Stachler Elyse</a>, <a href="/search?value1=Xavier+Fernandez-Cassi&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fernandez-Cassi Xavier</a>, <a href="/search?value1=Niko+Beerenwinkel&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Beerenwinkel Niko</a>, <a href="/search?value1=Tamar+Kohn&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Kohn Tamar</a>, <a href="/search?value1=Christoph+Ort&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Ort Christoph</a>, <a href="/search?value1=Timothy+R+Julian&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Julian Timothy R</a></span>. Inferring transmission fitness advantage of SARS-CoV-2 variants of concern from wastewater samples using digital PCR, Switzerland, December 2020 through March 2021. <a href="/content/ecdc">Euro Surveill.</a> 2022;27(10):pii=2100806. <a href="https://doi.org/10.2807/1560-7917.ES.2022.27.10.2100806" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2022.27.10.2100806</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 02 Aug 2021;&nbsp;&nbsp; <span class="generated">Accepted</span>: 21 Jan 2022 </span> </p>
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