RT Journal Article SR Electronic T1 Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2 JF Science Translational Medicine FD American Association for the Advancement of Science SP eabe2555 DO 10.1126/scitranslmed.abe2555 VO 12 IS 573 A1 Popa, Alexandra A1 Genger, Jakob-Wendelin A1 Nicholson, Michael D. A1 Penz, Thomas A1 Schmid, Daniela A1 Aberle, Stephan W. A1 Agerer, Benedikt A1 Lercher, Alexander A1 Endler, Lukas A1 Colaço, Henrique A1 Smyth, Mark A1 Schuster, Michael A1 Grau, Miguel L. A1 Martínez-Jiménez, Francisco A1 Pich, Oriol A1 Borena, Wegene A1 Pawelka, Erich A1 Keszei, Zsofia A1 Senekowitsch, Martin A1 Laine, Jan A1 Aberle, Judith H. A1 Redlberger-Fritz, Monika A1 Karolyi, Mario A1 Zoufaly, Alexander A1 Maritschnik, Sabine A1 Borkovec, Martin A1 Hufnagl, Peter A1 Nairz, Manfred A1 Weiss, Günter A1 Wolfinger, Michael T. A1 von Laer, Dorothee A1 Superti-Furga, Giulio A1 Lopez-Bigas, Nuria A1 Puchhammer-Stöckl, Elisabeth A1 Allerberger, Franz A1 Michor, Franziska A1 Bock, Christoph A1 Bergthaler, Andreas YR 2020 UL http://stm.sciencemag.org/content/12/573/eabe2555.abstract AB Austria was an early hotspot of SARS-CoV-2 transmission due to winter tourism. By integrating viral genomic and phylogenetic analyses with time-resolved contact tracing data, Popa et al. examined the fine-scale dynamics of viral spread within and from Austria in the spring of 2020. Epidemiologically defined phylogenetic clusters and viral mutational profiles provided evidence of the ongoing fixation of two viral alleles within transmission chains and enabled estimation of the SARS-CoV-2 bottleneck size. This study provides an epidemiologically contextualized, high-resolution picture of SARS-CoV-2 mutational dynamics in an early international transmission hub.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.