Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2

Popa, Alexandra; Genger, Jakob-Wendelin; Nicholson, Michael D.; Penz, Thomas; Schmid, Daniela; Aberle, Stephan W.; Agerer, Benedikt; Lercher, Alexander; Endler, Lukas; Colaço, Henrique; Smyth, Mark; Schuster, Michael; Grau, Miguel L.; Martínez-Jiménez, Francisco; Pich, Oriol; Borena, Wegene; Pawelka, Erich; Keszei, Zsofia; Senekowitsch, Martin; Laine, Jan; Aberle, Judith H.; Redlberger-Fritz, Monika; Karolyi, Mario; Zoufaly, Alexander; Maritschnik, Sabine; Borkovec, Martin; Hufnagl, Peter; Nairz, Manfred; Weiss, Günter; Wolfinger, Michael T.; von Laer, Dorothee; Superti-Furga, Giulio; Lopez-Bigas, Nuria; Puchhammer-Stöckl, Elisabeth; Allerberger, Franz; Michor, Franziska; Bock, Christoph; Bergthaler, Andreas

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 10(3) 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.