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

Abstract

Epidemiological and genomic analyses uncover viral mutational dynamics and transmission bottleneck size during the early COVID-19 pandemic in Austria.

Tracking and tracing SARS-CoV-2 mutations

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.

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 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.