How much should we sequence? An analysis of the Swiss SARS-CoV-2 surveillance effort
Author:
Wegner FannyORCID, Cabrera-Gil BlancaORCID, Araud Tanguy, Beckmann Christiane, Beerenwinkel NikoORCID, Bertelli Claire, Carrara Matteo, Cerutti Lorenzo, Chen ChaoranORCID, Cordey Samuel, Dumoulin Alexis, du Plessis Louis, Friedli Marc, Gerth Yannick, Greub Gilbert, Härri Adrian, Hirsch Hans, Howald Cedric, Huber Michael, Imhof Alexander, Kaiser Laurent, Kufner Verena, Leib Stephen L.ORCID, Leuzinger Karoline, Lleshi Etleva, Lucchini Gladys Martinetti, Mäusezahl Mirjam, Moraz Milo, Neher RichardORCID, Nolte Oliver, Ramette AlbanORCID, Redondo Maurice, Risch Lorenz, Rohner Lionel, Roloff Tim, Schläpfer Pascal, Schneider Katrin, Singer Franziska, Spina Valeria, Stadler Tanja, Studer Erik, Topolsky IvanORCID, Trkola Alexandra, Walther Daniel, Wohlwend Nadia, Zehnder Cinzia, Neves AitanaORCID, Egli AdrianORCID,
Abstract
AbstractBackgroundDuring the SARS-CoV-2 pandemic, many countries directed substantial resources towards genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats.AimWe aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic dataset from Switzerland, comprising more than 143k sequences.MethodsWe employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters.ResultsThe impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively.ConclusionA genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage dependent – something that is unknown at the time of sequencing – and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.
Publisher
Cold Spring Harbor Laboratory
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