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

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
emergingMutations
Epidemiologically validated infector-infectee pairs
Bottleneck size values of infector-infectee pairs
Intra-patient viral populations

Supplementary Data

Data fileDescription
S1Sample and sequencing information of the 572 samples and the controls.
S2Acknowledgements for SARS-CoV-2 genome sequences derived from GISAID. 
S3Epidemiological clusters referred to in this study. 
S4Transmission chain and sample information for ClusterA/ClusterAL and family-related cases. 
S5Clinical information of patients with COVID-19 relating to Figure 5 and Figure S5. 

Data Availability

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

Code availability

ScriptsDescription
Pipeline for sample processingMapping, Genome Reconstruction and Low Frequency Variant Calling.
Pipeline for phylogenetic analysesScripts for the reconstruction of global phylogeny (Global), phylogeny of Austrian strains (OnlyAustrian) and phylogeny of early European strains (EarlyEuropean).
Mutational profile along the genomesThe code to compute the mutational profile across the genome as well as the rate of mutation according to genomics context.
Variant analysisInput data, R markdown script and output data for sample characteristics figures and all the analyses concerning low frequency variants across samples.
Bottleneck size computationsThe 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