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

Study overview

Superspreading events shape the COVID-19 pandemic. Their rapid identification and containment are essential for disease control. Here we provide a national-scale analysis of SARS-CoV-2 superspreading 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 the mutational dynamics, including the observation of a low-frequency mutation that progressed to fixation within the infection chain. Time-resolved virus sequencing unveiled viral mutation dynamics within individual COVID-19 patients, while 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.

Phylogenetic-epidemiological analyses reveal clusters of infection

Emergence and spreading of a new mutation

Epidemiologically validated infector-infectee pairs

Bottleneck size values of infector-infectee pairs

Intra-patient viral populations

Supplementary Data

Data file	Description
S1	Sample and sequencing information of the 572 samples and the controls.
S2	Acknowledgements for SARS-CoV-2 genome sequences derived from GISAID.
S3	Epidemiological clusters referred to in this study.
S4	Transmission chain and sample information for ClusterA/ClusterAL and family-related cases.
S5	Clinical information of patients with COVID-19 relating to Figure 5 and Figure S5.

Data Availability

Data	Description
SARS-CoV-2 consensus sequences	All the consensus sequences in this study have been submitted to GISAID (Data file S2).
BAM files	The BAM files of reads mapped to the SARS-CoV-2 genome are deposited at EBI under the project number PRJEB39849.
Phylogenetic tree of Austrian samples	Metadata and phylogenetic tree information can be downloaded here.
Phylogenetic tree of European samples	Metadata and phylogenetic tree information can be downloaded here.
Phylogenetic tree of Global build.	Metadata and phylogenetic tree information can be downloaded here.

Code availability

Scripts	Description
Pipeline for sample processing	Mapping, Genome Reconstruction and Low Frequency Variant Calling.
Pipeline for phylogenetic analyses	Scripts for the reconstruction of global phylogeny (Global), phylogeny of Austrian strains (OnlyAustrian) and phylogeny of early European strains (EarlyEuropean).
Mutational profile along the genomes	The code to compute the mutational profile across the genome as well as the rate of mutation according to genomics context.
Variant analysis	Input data, R markdown script and output data for sample characteristics figures and all the analyses concerning low frequency variants across samples.
Bottleneck size computations	The scripts for computing bottleneck sizes between infector-infectee pairs.

Citation

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

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

^† - Equal contribution
^‡ - Equal contribution
* - Corresponding author: abergthaler@cemm.oeaw.ac.at