January 8, 2021

expert reaction to study using genomic epidemiology to look at COVID-19 transmission chains during the first wave in the UK

A study published in Science uses genomic epidemiology to trace COVID-19 transmission chains during the first wave in the UK through time and space.

Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“Various members of this team have been applying similar phylogenetic techniques to other viruses – including influenza, HIV, Ebola, Zika  over the years, and some of this work was shown earlier on their virological.org website.

“It is nice to see that very few of the UK transmission chains, overall (0.4%) were actually imported from China, with most being imported instead from other European countries (Spain, France, Italy) – as many Chinese students and members of the community received varying degrees of abuse for ‘bringing the virus into the UK’ during the early stages of the pandemic – which now seems unjustified.

“Another part of the study (page 6) was interesting – if expressed rather diplomatically: “These observations indicate substantial dissemination of a subset of lineages across the UK and suggest many regions experienced a series of introductions of new lineages from elsewhere, potentially hindering the impact of local interventions”.  Which potentially suggests less than optimal adherence to local travel restrictions during the first pandemic wave and national lockdown in the UK.

“Such viral phylogenetic studies are always limited by the sampling method used, and the team here quite rightly state that the proportion of samples sequenced for analysis across the multiple countries was relatively low, so there is always a risk of the unsampled or unsequenced  ‘missing link’ being absent in the dataset.

“Also, the sampling was not random, with some locations/countries being able to contribute more samples for sequencing than others (like the UK) – and being potentially over-represented in the final dataset/analysis.

“But this is the most comprehensive analysis so far with this type of data, and is still likely to be a fairly accurate description of how this virus was spreading across the UK during the first pandemic wave.”

Prof Ed Feil, Professor of Microbial Evolution, University of Bath, said:

“This study by du Plessis and colleagues provides a superb illustration of the power of genomics, when combined with other lines of evidence, for dissecting out the mechanics of an epidemic in unprecedented detail.  By retrospectively identifying and characterising all the lineages that spread within the UK population over the early weeks of the epidemic, the authors address the “black hole” in epidemiological surveillance that exists between very fine-scaled dynamics (short-transmission chains between individuals) and the big-picture trends of the outbreak as a whole.

“A few key patterns stand out.  Firstly, the variation in lineage size follows a ‘power law’ distribution, which means that a high proportion of transmission events (and hence cases) are associated with a small number of very abundant lineages.  Conversely, there are a large number of very rare lineages.  The rare lineages are much more geographically restricted and more much more prone to extinction after the March lockdown.  It is important to note that the authors are not suggesting that there were any biological differences between the lineages at this point (in contrast to the new variant that arose later), but that these patterns are a consequence of the underlying mathematics of disease spread.

“The authors are also able to compare the contributions of community spread with the introduction of new lineages (both are important, but at different times) and regional differences that are likely due to the ‘connectedness’ of different cities.

“The authors also propose a novel measure (the estimated importation intensity) which combines the amount of opportunity for an introduction to occur from elsewhere (i.e. the amount of travel) with the chance that an introduction will happen (determined by the case load).  They use this index to show how importations changed over time from different countries, and also the lag time between when an introduction likely occurred and when it was first picked up by sampling and sequencing.

“With respect to the current outbreak, the work confirms the importance of early interventions in snuffing out newly introduced lineages before they get a chance to become widespread.  Perhaps more importantly, however, the analysis provides an excellent roadmap and exemplar for how large genome sequence datasets can help lay bare in exquisite detail the anatomy of an epidemic.”

‘Establishment & lineage dynamics of the SARS-CoV-2 epidemic in the UK’ by Louis du Plessis et al. was published in Science at 15:00 UK time on Friday 8 January 2021.

Declared interests

None received.