Abstract
Superspreading events shaped the coronavirus disease 2019 (COVID-19) pandemic, and their rapid identification and containment are essential for disease control. Here, we provide a national-scale analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading during the first wave of infections in Austria, a country that played a major role in initial virus transmissions in Europe. Capitalizing on Austria's well-developed epidemiological surveillance system, we identified major SARS-CoV-2 clusters during the first wave of infections and performed deep whole-genome sequencing of more than 500 virus samples. Phylogenetic-epidemiological analysis enabled the reconstruction of superspreading events and charts a map of tourism-related viral spread originating from Austria in spring 2020. Moreover, we exploited epidemiologically well-defined clusters to quantify SARS-CoV-2 mutational dynamics, including the observation of low-frequency mutations that progressed to fixation within the infection chain. Time-resolved virus sequencing unveiled viral mutation dynamics within individuals with COVID-19, and epidemiologically validated infector-infectee pairs enabled us to determine an average transmission bottleneck size of 103 SARS-CoV-2 particles. In conclusion, this study illustrates the power of combining epidemiological analysis with deep viral genome sequencing to unravel the spread of SARS-CoV-2 and to gain fundamental insights into mutational dynamics and transmission properties.
Highlights
The SARS-CoV-2 pandemic has already infected more than 20 million people in 188 countries, causing 737,285 deaths globally as of August 11, 2020 and extraordinary disruptions to daily life and national economies [1, 2]
Unprecedented global research efforts are underway to counter the COVID-19 pandemic around the globe and its pervasive impact on health and socioeconomics. These efforts include the genetic characterization of SARS-CoV-2 to track viral spread and to investigate the viral genome as it undergoes changes in the human population
We leveraged deep viral genome sequencing in combination with nationalscale epidemiological workup to reconstruct Austrian SARSCoV-2 clusters that played a substantial role in the international spread of the virus
Summary
The SARS-CoV-2 pandemic has already infected more than 20 million people in 188 countries, causing 737,285 deaths globally as of August 11, 2020 and extraordinary disruptions to daily life and national economies [1, 2]. The international research community rapidly defined pathophysiological characteristics of the Coronavirus Disease. Clustered outbreaks and superspreading events of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a particular challenge to pandemic control [7,8,9,10]. We still know comparatively little about fundamental properties of SARS-CoV-2 genome. First release: 23 November 2020 stm.sciencemag.org (Page numbers not final at time of first release) 1 evolution and transmission dynamics within the human population. Low-frequency mutations and their changes over time within individual patients can provide insights into the dynamics of intra-host evolution. The resulting intra-host viral populations represent groups of variants with different frequencies, whose genetic diversity contributes to fundamental properties of infection and pathogenesis [15, 16]
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