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.

Podcast: Burrow-dwelling solitary bees and the winter of their demise

 

 

Guest podcast by UTSC Biology students: Gillian Sauder and Nyx Radu

Burrow-dwelling solitary bees determine their entry into winter diapause based solely based on temperature, this raises the question; are rising global temperatures delaying diapause in these bees? And how will these diapause delays impact their limited energy reserves and survival rates? Find out on the first and only episode of the hit podcast that one person described as "as educational and depressing as a real conservation biology degree" and which alien archaeologists will describe as "an exemplary demonstration of humanity's damning tendency to joke about their problems rather than fix them."  Life: How It's All Dying (Winter Edition) is available now on a blog near you.

 

 

COVID-19 and nature: Is wildlife conservation also in “lockdown”?

Guest post by Nina Adamo, Masters of Environmental Science Candidate at the University of Toronto-Scarborough

Within the surge of news coverage for the COVID-19 pandemic, you may have heard about the increase in the reporting of wildlife sightings in some urban areas across the globe, such as in this CBC article. With less people venturing outside of their homes in efforts to prevent the spread of the coronavirus, the media in multiple countries around the globe have been reporting more sightings of wildlife that are usually rarely or uncommonly seen in suburban and urban areas.^6,7 This was the case when a herd of Kashmir goats were seen strolling through the deserted streets of a town in Wales during the lockdown.⁷

A herd of Kashmir goats roaming the empty streets of a town in Wales.³

This also happened in Toronto, Canada this past summer, where foxes were seen denning in typically busy areas of the city during lockdown.² To read more about the Tale of Toronto’s boardwalk foxes, check out this article in Maclean’s magazine. What does this unusual and greater number of wildlife sightings in urbanized areas mean for wildlife behaviour and wildlife conservation as a whole?

Fox kits on the boardwalk of Woodbine beach in the city of Toronto, Canada.⁴

The “rolling lockdowns” implemented as strategies to contain the novel coronavirus have severely restricted human activities, and have had cascading effects through public health systems and economies.⁶ What is less clear however, is what impacts this sudden change in human behaviour may have on wildlife and what the long-term implications are for the fate of wildlife conservation across the globe and into the future. The interaction between our societal response to COVID-19 and wildlife is a novel and emerging topic that scientists have only just begun to investigate. Unsurprisingly, initial findings tell a complex story, where lockdowns have had both positive and negative impacts on wildlife and the conservation of biodiversity.^1,5,6

Initial positive effects of lockdowns on the environment, in general, include reductions in industrial activities and manufacturing, and restrictions on the transport of natural resources, leading to a decrease in global emissions and an increase in air and water quality.^1,5 Other studies report decreases in noise pollution leading to an increase in sightings of animals in cities and harbours, along with reduced numbers of animals being killed by ships in waterways and by vehicles on roads.^1,6 Similarly, a study conducted in Italy, the first country to implement a lockdown, found a greater proportion of sightings of species such as the crested porcupine in suburban and urban areas in 2020 compared to previous years.⁶ The same study also found evidence for an increase in the abundance and breeding success of certain species of birds during lockdown in urban areas, likely due to general decrease in the presence of humans.⁶

A crucial point to consider about all of these positive observed effects is that many of these effects, such as the presence of uncommon animals in urban areas, are likely to only be temporary and prone to reversal once restrictions are lifted and humans begin to revert back to pre-lockdown behaviours.^5,6 It is also worth noting that many observed increases in animal numbers under lockdown conditions could have resulted from an increase in observation effort with more people participating in hobbies such as birding due to restrictions on other activities during lockdowns.⁶ Similarly, the greater detection of bird species could have been attributed to an increase in detection rates because of a reduction of background traffic noise with less traffic volume in lockdown conditions.⁶

There is great concern that the COVID-19 pandemic will severely hinder efforts to conserve biodiversity in the present as well as in the long term.⁶ During lockdown, there have been substantial delays in both species at risk management efforts and invasive species control programs,⁶ reduced funding available for conservation because of overstressed economies, reductions in wildlife-based tourism due to travel restrictions, and governmental capacity generally being prioritized for COVID-19 relief measures.^1,5 The pandemic has undoubtedly put a strain on our capacity for conservation, and many initiatives will be playing catch-up to make up for precious lost time, where many of these conservation efforts are focused on species that are already teetering on the brink.

Increased human threats to nature are also expected to occur as a result of the lockdowns.^5,6 As more people, especially in rural areas, are forced to navigate pandemic-driven economic downturns, they may have no choice but to turn to protected areas for resources.⁵ In addition to this, the reduced funding available for hiring patrol staff such as park rangers in protected areas can result in a lower likelihood of detecting poachers and can lead to an increase in illegal killing of wildlife, which has been the pattern already observed in multiple places across the globe including Europe, Africa, and Asia.^1,5,6

Schematic of the potential impacts of the COVID-19 pandemic on different areas related to the conservation of wildlife in Africa, with the arrows indicating the directionality of these impacts.⁵

The surge of research examining the interaction between societal response to COVID-19 and wildlife tells a complex story.⁶ Although there were some positive effects of the lockdown observed on wildlife, these will likely only be temporary until restrictions are lifted, but the potential negative impacts could have long-lasting effects on the conservation of biodiversity.^5,6 Furthermore, activities focused on the conservation of species and habitats can also help to reduce the risk of future pandemics as the restrictions put in place to protect certain species and their habitats can help to reduce our exposure to species that are a high risk for virus transfer to humans, leading to a lower risk of future outbreaks and subsequent pandemics.⁵

Overall, although the COVID-19 lockdowns have shown some initial positive impacts on the environment and wildlife, there are significant risks associated with these lockdowns that may negatively impact the effectiveness of wildlife conservation. In order to effectively prevent the accelerated loss of biodiversity that could result from lockdowns, countries must ensure funding for conservation actions is not neglected.

  

References

1. Bates, A. E., Primack, R. B., Moraga, P., & Duarte, C. M. (2020). COVID-19 pandemic and associated lockdown as a “Global Human Confinement Experiment” to investigate biodiversity conservation. Biological Conservation, 248, 108665. https://doi.org/10.1016/j.biocon.2020.108665
2. Dhopade, P. (2020, July 7). The tale of Toronto’s boardwalk foxes. Retrieved from https://www.macleans.ca/society/environment/toronto-boardwalk-foxes-coronavirus-lockdown/  
3. Furlong, C. (2020, April 5). A herd of Kashmir goats invaded a Welsh seaside resort after the coronavirus lockdown left the streets deserted. Wildlife take to the streets as people stay indoors. [Getty Images]. Retrieved October 26, 2020 from https://www.cbc.ca/news/world/photos-wildlife-animals-take-to-streets-as-people-take-shelter-indoors-1.5519538
4. Lautens, R. (2020, July 7). A few of the young kits at Woodbine Beach in Toronto; when passersby began taking selfies with the animals, a local wildlife centre intervened. The tale of Toronto’s boardwalk foxes. [Image]. Retrieved October 23, 2020 from https://www.macleans.ca/society/environment/toronto-boardwalk-foxes-coronavirus-lockdown/
5. Lindsey, P., Allan, J., Brehony, P., Dickman, A., Robson, A., Begg, C., Bhammar, H., Blanken, L., Breuer, T., Fitzgerald, K., Flyman, M., Gandiwa, P., Giva, N., Kaelo, D., Nampindo, S., Nyambe, N., Steiner, K., Parker, A., Roe, D., … Tyrrell, P. (2020). Conserving Africa’s wildlife and wildlands through the COVID-19 crisis and beyond. Nature Ecology & Evolution, 4(10), 1300–1310. https://doi.org/10.1038/s41559-020-1275-6
6. Manenti, R., Mori, E., Di Canio, V., Mercurio, S., Picone, M., Caffi, M., Brambilla, M., Ficetola, G. F., & Rubolini, D. (2020). The good, the bad and the ugly of COVID-19 lockdown effects on wildlife conservation: Insights from the first European locked down country. Biological Conservation, 249, 108728. https://doi.org/10.1016/j.biocon.2020.108728
7. Wildlife take to the streets as people stay indoors. (2020, April 5). Retrieved from https://www.cbc.ca/news/world/photos-wildlife-animals-take-to-streets-as-people-take-shelter-indoors-1.5519538

The fork in the road: science versus denialism and conspiracy theories

The world is awash in information. Never before have people had as much access to humanity’s collective knowledge as we do today. You want to know when the Normans conquered England? How many people use Weibo? Or what Machu Picchu would have looked like in its glory days? Simply pull out your phone and ask Siri. 

 

This cornucopia of knowledge should mean that people are in the position to make the best decisions possible. From the insurance plans that best fit their needs to voting for candidates or political parties that support policies that return optimal outcomes for individuals and society as a whole. Beyond individuals, this wealth of information should mean that evidence-based policy would be easy to pursue and outcomes for nations continually improving.

 

However, this is clearly not the case. The availability of knowledge doesn’t mean that evidence, fact and truth are utilized. Preconceived belief and ideology are important filters through which evidence is evaluated. Yet, what is really disheartening about the use of knowledge and evidence is how others (individuals and organizations) with political and economic agendas filter and manipulate what is channelled to various audiences.

 

While we might naively refer to the modern era as one based on information and the democratization of evidence and knowledge, the reality is that we live in the era of disinformation. Disinformation is the active and knowing creation and spread of false information, like politicians saying a fair election was stolen. Misinformation is the cancerous offspring of disinformation, where this false information is shared by those unaware of its nefarious origins. Disinformation and misinformation have the power to derail robust democracies and motivate atrocities.

 

The study of the origins and valuation of knowledge is a complex, convoluted and challenging area to say the least. But it is not esoteric nor just academic. Knowledge and understanding are the cornerstone of societal well-being, technological development and ultimately underpin democracy. Public policy driven by misinformation and dismissal of basic facts is simply ill-equipped to deal with many of the problems we face. This is easily showcased by the dismal, and frankly embarrassing, chaotic COVID-19 response in the United States -a clear failure for proponents of evidence-based policy.

 

Knowledge and belief arise through a number of different endeavours that span social influences, logic and reasoning, and, importantly, the empirical claims of science. Science is the process by which we assess testable claims about the world. Scientists use accumulated knowledge and evidence to formulate questions or predictions and then ultimately assess these against experiments and observation. We commonly ascribe science to the scientific method, but what scientists actually do and how they go about developing explanations and testing them is actually quite a bit more complicated. Philosophers of science, from Popper to Kuhn to Lakatos and on to Lauden have argued about what demarcates science from other knowledge-gaining exercises and these debates have, in some ways, been mired by the reliance on a scientific method that may or may not exist (see Lee McIntyre’s The Scientific Attitude for a wonderful overview).

 

The best way to think about science is to use McIntyre’s lead, where science is both a process and worldview. It is a process because it has rules in place to guide how we assess claims about the world. Perhaps more importantly, as a worldview that scientists subscribe to, we are willing to test our explanations against fair and unbiased evidence and are willing to alter our belief in light of countervailing evidence. Explanation and belief are constantly assessed and refined, or in some cases completely dropped, because we allow the real world to correct us. I’ve certainly gone through this process and have changed my thinking about the theories that I work on. More than once.

 

 

As the figure above indicates, there are multiple avenues to gain knowledge and empirical science is one of them. I take a broad view of science, so that it would include a lot of what is done in social sciences. Economics, for example, can certainly answer the question, based on more than 80 years of empirical evidence from neoliberal policies, of whether tax cuts or infrastructure investment result in greater economic growth (it’s the latter).

 

Science is one route to knowledge, insight and introspection about ourselves and our place in the universe. However, on matters of the observable world, it is the most important. Science starts with testable questions which necessitate the collection and assessment of evidence (‘facts’), but something can go wrong here. People who don’t follow the rules of science (like objectivity, honesty and transparency) and have a pre-ordained conclusion can simply use only evidence that confirms their belief (confirmation bias) while downplaying damning evidence that shoots their theory full of holes (refutation bias). Once we hit this fork, we go down the path to denialism, pseudoscience and conspiracy theory.

 

We throw around these last three terms a lot when talking about anti-science and anti-fact movements like QAnon, anti-vaccine movements and flat-Earth proponents, but they are not actually synonyms. Though these three terms are clearly interrelated, and many irrational movements invoke all three.

 

Denialism refers to the refusal to believe empirical evidence that casts doubt on one’s belief or ideology. No amount of negative evidence can change the mind of an adherent. Positive evidence is given extremely high weight, often without critically examining the origins of evidence.  But evidence is often not an important ingredient, it is just convenient when it reinforces belief. 

 

Pseudoscience uses the language of science and even purports to uses empirical evidence and experimentation. However, the preferred explanation is assumed to be true, and all that is required is the evidence support it. Opposing explanations are assumed to be wrong, regardless of empirical support. A classic example was the shift from young-Earth creationism (which usually fell firmly in the Denialism camp) to intelligent design (ID). ID attempted to avoid the language of creationism and instead used technical-sounding concepts like ‘irreducible complexity’ to conclude that a creator was a necessary ingredient to explain life. Unfortunately, for ID, proponents’ claims have not been able to withstand rigorous testing, but proponents will still cling to fragile evidence to support their beliefs. 

 

Finally, conspiracy theory has much in common with denialism, and it can be argued that you need to be a denialist in order to truly be a conspiracy theorist. However, in order to support their claims, they go a step further and see a vast collusion of nefarious actors whose primary agenda is to undermine the ‘truth’. Take for example the recent claims of election fraud in the USA. Adherents to this conspiracy theory are willing to believe that dead dictators, Democrat leaders and a vast network of thousands of election volunteers are all part of an organized attempt to change the outcome of an election. Without e-mails. Or social media posts. Or any other evidence. Compare this to the fact that average people could easily figure out the identities of members of the mob that stormed Congress because of extensive social media threads and verbal communication with friends and neighbours. This strange juxtaposition can only lead us to one of two conclusions. Either there was no election rigging conspiracy, or those who stormed the Capital are idiots and the thousands of election stealers are just so much smarter.

 

In all three of these cases, some form of authority or ideology is given more weight than reality. I have a couple of hypotheses why this happens, and especially in the USA, where the nationalistic hubris creates a large gap between the belief about how great one is compared to their reality, and so instead of accepting reality, feelings and scapegoats trump fact.

 

The dismissal of evidence has become commonplace in political life. No one said it better than Newt Gringerich. He basically says that conservative voters believe America is more dangerous today than in the past, and when the newsperson confronts him with the fact that crime has been on a downward trajectory for a long time and that we are statistically safer today than a couple of decades ago, he responds that ‘Liberals’ might have facts that are theoretically true, but his facts are true too. Remember Sean Spicer’s ‘alternative facts’, and this thinking has been around for a while. Have conclusion, need fact.

 

Christmas day 2020, Wisconsin pharmacist Steven Brandenburg purposely destroyed hundreds of dosesof the Moderna COVID19 vaccine. Turns out that Mr. Brandenburg believes that the world is flat and that the Moderna vaccine was designed to harm people and also includes microchips for tracking. While we might chuckle at the absurdity of these believes, there is a deeper, more troubling issue at play. Mr. Brandenburg is a pharmacist. Meaning that he not only has scientific training, but also needs to make evidence-based decisions to help patients. As a supposedly scientifically literate person, he could have easily devised ways of testing his claims. For example, take a plane to Asia, then another to Europe, and then back to the USA. There, the world is not flat. As for microchips in vaccines, a simple compound microscope ought to be enough to observe these.

 

So, if a pharmacist is not willing to put the effort into testing easily refutable claims, why would we expect our bank teller, auto mechanic or Ted Cruz? This goes to the core of the problem. Given the politics of Truth and fact, science and scientists no longer have any authority for many people. In fact, just being a scientist might be enough to get you dismissed as an agenda peddler or a member of some number of absurd conspiracy theories.

 

There is no doubt that vaccines have saved more lives than almost any other medical technology. Yet no other medical treatment or intervention has elicited more skepticism and outright rage than vaccines. And yet there is no rational reason for this, the evidence is very clear. But, there is a denialist and alarmist reason that plays on parents’ anxiety about the health of their children and mistrust of science. 

 

In 1998, Andrew Wakefield published a paper in the prestigious journal, Lancet, in which he reported a link between MMR vaccines and autism. This paper should have never been published. It was based on a sample size of 12 children, and from which there was evidence that Wakefield altered data and records. This paper was retracted by the journal, which is pretty much the worst public humiliation a scientist can experience. It is a recognition that you broke the sacred rules of science and it is a shame you wear for the rest of your career. Despite this public shaming, non-scientific audiences gravitated to his messaging in books and paid lectures.

 

Today, many thousands of people believe that vaccines are bad for children and might cause autism. Of course, these same people would probably have no problem taking antibiotics for an infection, receiving chemotherapy for cancer or eating a hotdog when hungry, despite the fact they probably can’t tell you what exactly is in these. Why vaccines? That is an interesting question. Maybe it’s just serendipity that this was the fraud target of Wakefield, or maybe it’s because of the violation of having a needle pierce your skin, or maybe it is because of the undeniable success of vaccines.

 

This vaccine denialism not only resulted in the re-emergence of nearly eradicated childhood diseases in places like Paris and Los Angeles, but it wasted money and time that could have been put to better use research new therapies. The response required ever increasing numbers of studies to show that there were no links between vaccines and autism. In one of the largest assessments, Anders Hviid and colleagues examined and analyzed the health records of more than 650,000 Danish children for more than 10 years and they simply didnot find any links between MMR vaccines and autism.

 

If you happen to be one that doubts the safety and efficacy of vaccines, ask yourself why, and where you are getting your information from. Then ask yourself if you were, unfortunately, diagnosed with cancer, would you trust your doctor’s request that you start radiation or chemotherapy? If so, despite not really understanding what constitutes ‘chemotherapy’, you’d trust your doctor's knowledge and expertise. Why would you dismiss this same doctor when it came to vaccine advice? You can’t have it both ways, that is irrational.

 

So, where does this leave us? In a quagmire for sure. But it also means that those of us who practice, use or teach empirical science have the knowledge and scientific understanding to engage in dialogues about important issues, whether that is about climate change or vaccines. It doesn’t mean we need to be political (but we should engage with political structures), and we don’t need to be dismissive. We can ask questions to understand peoples’ mistrust or where they are getting their information from. I find that the best way to engage is to be affirmational and dispassionate (which can be hard for me). I recently engaged in a conversation with someone who wasn’t going to get a COVID vaccine and asked a bunch of ‘why’ questions and then started my statements with phrases like “I can understand why you’d be unsure…” and I laid out the medical and public health facts about vaccines.

 

The only way to counter disinformation is with the light of evidence. Not everyone will abandon their conspiracy theories, but many have been fed misinformation, and scientific understanding and fact can really help people make better decisions for themselves.