SARS-CoV-2 transmission routes from genetic data: A Danish case study

Abstract

Background: The first cases of COVID-19 caused by the SARS-CoV-2 virus were reported in China in December 2019. The disease has since spread globally. Many countries have instated measures to slow the spread of the virus. Information about the spread of the virus in a country can inform the gradual reopening of a country and help to avoid a second wave of infections. Our study focuses on Denmark, which is opening up when this study is performed (end-May 2020) after a lockdown in mid-March.

Methods: We perform a phylogenetic analysis of 742 publicly available Danish SARS-CoV-2 genome sequences and put them into context using sequences from other countries.

Results: Our findings are consistent with several introductions of the virus to Denmark from independent sources. We identify several chains of mutations that occurred in Denmark. In at least one case we find evidence that the virus spread from Denmark to other countries. A number of the mutations found in Denmark are non-synonymous, and in general there is a considerable variety of strains. The proportions of the most common haplotypes remain stable after lockdown.

Conclusion: Employing phylogenetic methods on Danish genome sequences of SARS-CoV-2, we exemplify how genetic data can be used to trace the introduction of a virus to a country. This provides alternative means for verifying existing assumptions. For example, our analysis supports the hypothesis that the virus was brought to Denmark by skiers returning from Ischgl. On the other hand, we identify transmission routes which suggest that Denmark was part of a network of countries among which the virus was being transmitted. This challenges the common narrative that Denmark only got infected from abroad. Our analysis concerning the ratio of haplotypes does not indicate that the major haplotypes appearing in Denmark have a different degree of virality.

Fig 1. The tree building process as a flow chart.

Fig 2. Haplotypes over time.

Top panel: relative frequencies of major haplotypes in Denmark over time; bottom panel: total number of sequences over time. Both graphs are based on seven-day rolling averages.

Fig 3

(a) Phylogenetic tree for sequences containing mutation C15842A. From the representation one can read of the chain mutations starting at C15842A. The second mutation shown is C15842A, followed by C12781T. After that, it trifurcates into G22103C, A23975G and C25499T. (b) Chain of mutations starting at C15842A.

Fig 4. Phylogenetic tree for sequences containing mutation C1302T.

From the representation one can read of the chain mutations starting at C1302T. The second mutation is C11074T, followed by C29095T. Subsequently, the chain bifurcates into C619T and A9280G followed by C7164T.

Fig 5

(a) Spread of the strain with haplotype C1302T. The figure shows the likely spread of the strain with haplotype C1302T from Denmark to other Northern European countries. Within Denmark, it also mutated further and gave rise to the chain of mutations displayed in (b). (b) Chain of mutations starting at C1302T.