Increasing diversity of COVID-19 strains: insights into evolutionary divergence and public health

 To be clear, I am not a virologist, nor am I a public health expert. But I do know how to analyze patterns of evolutionary diversity. Research into the SARS-CoV-2 virus that has given rise to the COVID-19 pandemic has greatly enhanced our understanding of global disease dynamics, mRNA vaccines and public health responses to a global crisis. But the COVID-19 pandemic also has the potential to provide fundamental insights into basic ecological and evolutionary processes. 

While a lot has been written about how COVID-19 lock-downs have had noticeable repercussions on air quality and wildlife in cities, the virus lends itself as a microcosm into natural world dynamics. SARS-CoV-2 is now the most studied non-human organism on Earth, and we've witnessed its spread across the globe (which provides insights into invasion biology), it has spread exponentially in populations at times (showcasing the power of models to predict spread), and its rapid diversification is evolution in real time.

Understanding how SARS-CoV-2 strain diversity is generated is of fundamental importance for public health policies. And SARS-CoV-2 is evolving and diversifying. In Ontario, Canada, we have a wonderful resource from Public Health Ontario that publishes data on the evolution of strain diversity and provides a wonderful graphical interface. This interface focuses on the SARS-CoV-2 phylogeny (that is the evolutionary family tree connecting strains to their ancestors) in Ontario.

An example phylogeny

Using their open data, I addressed a simple question, is the evolutionary diversity (measured by the distances separating strains) increasing over time?

To test this, I calculated a statistical measure called the standardized effect size of the mean pairwise distances (SES.MPD) which quantifies the average distances separating strains standardized by random permutations (in this case 500 randomizations) so that a SES.MPD value of 0 means that the evolutionary diversity of a group of strains is no different than a same number of strains randomly selected from the phylogeny. Negative values mean that strains are more closely related on the phylogeny than you expect by chance (referred to as under-dispersed), and positive values mean strains are more distantly related (over-dispersed). I did these calculations for each month since the pandemic hit Ontario (March 2020) and for the seven different regions of Ontario.

Analysis of the standardized effect size of the mean pairwise distances (SES.MPD) of SARS-CoV-2 strains across the seven regions in Ontario since the start of the pandemic. The dashed horizontal line indicates a value of 0 (no different than random expectation) and points outside of the grey box are statistically significantly different than random.

What I found was that early on in the pandemic, the strains were under-dispersed, meaning that they were more closely related and genetically similar than expected by chance. But over time the dissimilarity between strains increases and by May 2021 (the last data in the graphs), many of Ontario's regions had significantly over-dispersed strains. This means that strains found in the populations in May 2021 were generally more dissimilar from one another than early on.

Why this matters is that vaccines and other treatments are typically developed on a single strain or from samples collected at a specific time point. If strains are relatively genetically similar, then it is highly probable that treatments will be successful across the strains. However, as strains diversify and become more dissimilar, then treatments might become less effective overall. 

Had the spreading infection been dominated by single strains, with very few newer strains replacing older ones, we would expect that the SES.MPD values remain below zero, and would make it easier to track strains and adapt treatments.

These patterns are also valuable for insights into ecology and evolution. We often look at SES.MPD values to interpret how different processes structure diversity (like competition, predation, pollution, etc.), but we often don't have good evidence of how historical evolutionary processes can drive SES.MPD differences. The plots above show that rapid evolutionary diversification results in linearly increasing SES.MPD values.

INTECOL & the future of community ecology for infectious diseases – August 21st 2013 - #INT13

This year's conference has a strong focus on infectious disease which included today's symposium Community ecology for infectious diseases organized by Joanne Lello.

Throughout the symposium a great deal of interesting questions related to host-parasite interactions being addressed with a diverse set of methods ranging from the mathematical biology of Andy Dobson, to the experimental C. elegans / pathogenic bacteria systems of Olivier Restif and Gregg Hurst, the wild rodent systems of Heike Lutermann, Andy Fenton, and Owen Petchey, and the next generation molecular techniques employed by Serge Morand.

However, it was Robert Poulin the keynote speaker who set the theme of the symposium to which many of the speakers kept returning: What are the future directions of parasite community ecology? Dr. Poulin began the session with an overview of the recent trends in parasite ecology over the last few decades and Lawton's view that community ecology is a mess (Oikos 1999 – 84: 177-192). The initial research done on host-parasite interactions was centred within the one host – one parasite framework, often dealing solely with the effect of the parasite on its host. This was then expanded to the one host – multi-parasite level, often investigating drivers of parasite species richness among hosts via comparative analyses and occasionally extending to parasite-parasite interactions though the use of null models. Although the data were available beforehand, only recently has the field moved into the domain of multi-host – multi-parasite interactions, now focusing on questions of infection dilution, meta-analyses of parasite richness, and describing the networks of interactions within these communities.

Looking ahead into the future of this discipline, Poulin suggested that researchers should expand beyond simple topological networks of associations to include the strength of interactions, potentially via energy flow, and the use of network analyses on smaller scales using individual hosts. Serge Morand also highlighted the need to develop and incorporate parasite phylogenies into these multi-host - multi-parasite communities. His talk highlighted recent advances in next generation sqeuenceing and how these techniques can be applied to parasite communities. One obvious advantage is that through molecular phylogenetics researchers will be able to define and quantify a higher degree of parasite diversity, but additionally molecular markers can be used to uncover unexpected host diversity or identify species that may be difficult to distinguish through traditional taxonomic keys. Morand continued to press the application of new techniques in immunogenetics and the integration of methods in molecular epidemiology with the theory of transmission and community ecology.

Finally Andy Dobson posited that in addition to pressing forward with our research into infectious disease, it is imperative that contemporary researchers revist the “best hits” of the past and address important issues that have fallen to the wayside. Primarily Dobson pointed out that mathematically, aggregation and virulence of parasites have been shown as important factors for determining parasite co-existence. However, the concept of aggregation is often left out of contemporary discussions although it will be important to determine natural forms of the aggregation distribution and also to attempt to make the link between immunity and aggregation of parasites in a multi-host – multi-parasite community.

Whether incorporating novel molecular and statistical techniques, exploring previously unstudied model systems, or revisiting the context of contemporary research, it is clear that community ecology and infectious disease has a promising future and that it has progressed greatly from the mess Lawton made it out to be in 1999.