[Journal of Theoretical Biology, 20 December 2022]

COVID-19 remains a major public health concern, with large resurgences even where there has been widespread uptake of vaccines. Waning immunity and the emergence of new variants will shape the long-term burden and dynamics of COVID-19. We explore the transition to the endemic state, and the endemic incidence in British Columbia (BC), Canada and South Africa (SA), to compare low and high vaccination coverage settings with differing public health policies, using a combination of modelling approaches. We compare reopening (relaxation of public health measures) gradually and rapidly as well as at different vaccination levels. We examine how the eventual endemic state depends on the duration of immunity, the rate of importations, the efficacy of vaccines and the transmissibility. These depend on the evolution of the virus, which continues to undergo selection. Slower reopening leads to a lower peak level of incidence and fewer overall infections in the wave following reopening: as much as a 60% lower peak and a 10% lower total in some illustrative simulations; under realistic parameters, reopening when 70% of the population is vaccinated leads to a large resurgence in cases. The long-term endemic behaviour may stabilize as late as January 2023, with further waves of high incidence occurring depending on the transmissibility of the prevalent variant, duration of immunity, and antigenic drift. We find that long term endemic levels are not necessarily lower than current pandemic levels: in a population of 100,000 with representative parameter settings (Reproduction number 5, 1-year duration of immunity, vaccine efficacy at 80% and importations at 3 cases per 100K per day) there are over 100 daily incident cases in the model. Predicted prevalence at endemicity has increased more than twofold after the emergence and spread of Omicron. The consequent burden on health care systems depends on the severity of infection in immunized or previously infected individuals.

[eLife, 30 November 2022]

The role of schools in the spread of SARS-CoV-2 is controversial, with some claiming they are an important driver of the pandemic and others arguing that transmission in schools is negligible. School cluster reports that have been collected in various jurisdictions are a source of data about transmission in schools. These reports consist of the name of a school, a date, and the number of students known to be infected. We provide a simple model for the frequency and size of clusters in this data, based on random arrivals of index cases at schools who then infect their classmates with a highly variable rate, fitting the overdispersion evident in the data. We fit our model to reports from four Canadian provinces, providing estimates of mean and dispersion for cluster size, as well as the distribution of the instantaneous transmission parameter β, whilst factoring in imperfect ascertainment. According to our model with parameters estimated from the data, in all four provinces (i) more than 65% of non-index cases occur in the 20% largest clusters, and (ii) reducing instantaneous transmission rate and the number of contacts a student has at any given time are effective in reducing the total number of cases, whereas strict bubbling (keeping contacts consistent over time) does not contribute much to reduce cluster sizes. We predict strict bubbling to be more valuable in scenarios with substantially higher transmission rates.

[BMC Genomics, 19 October 2022]

Background: The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the accuracy and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada.

Results: We found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high accuracy when predicting epidemiologically informed clusters from sequence data.

Conclusions: Our new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.

[Vaccine, 16 September 2023]

Background: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2.

Methods: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively.

Discussion: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.

[Journal of Mathematical Biology, 6 November 2023]

Almost all models used in analysis of infectious disease outbreaks contain some notion of population size, usually taken as the census population size of the community in question. In many settings, however, the census population is not equivalent to the population likely to be exposed, for example if there are population structures, outbreak controls or other heterogeneities. Although these factors may be taken into account in the model: adding compartments to a compartmental model, variable mixing rates and so on, this makes fitting more challenging, especially if the population complexities are not fully known. In this work we consider the concept of effective population size in outbreak modelling, which we define as the size of the population involved in an outbreak, as an alternative to use of more complex models. Effective population size is an important quantity in genetics for estimation of genetic diversity loss in populations, but it has not been widely applied in epidemiology. Through simulation studies and application to data from outbreaks of COVID-19 in China, we find that simple SIR models with effective population size can provide a good fit to data which are not themselves simple or SIR.

[Science Advances, 3 November 2023]

The seasonal influenza (flu) vaccine is designed to protect against those influenza viruses predicted to circulate during the upcoming flu season, but identifying which viruses are likely to circulate is challenging. We use features from phylogenetic trees reconstructed from hemagglutinin (HA) and neuraminidase (NA) sequences, together with a support vector machine, to predict future circulation. We obtain accuracies of 0.75 to 0.89 (AUC 0.83 to 0.91) over 2016–2020. We explore ways to select potential candidates for a seasonal vaccine and find that the machine learning model has a moderate ability to select strains that are close to future populations. However, consensus sequences among the most recent 3 years also do well at this task. We identify similar candidate strains to those proposed by the World Health Organization, suggesting that this approach can help inform vaccine strain selection.

[Nature Communications, 10 August 2023]

Serial intervals – the time between symptom onset in infector and infectee – are a fundamental quantity in infectious disease control. However, their estimation requires knowledge of individuals’ exposures, typically obtained through resource-intensive contact tracing efforts. We introduce an alternate framework using virus sequences to inform who infected whom and thereby estimate serial intervals. We apply our technique to SARS-CoV-2 sequences from case clusters in the first two COVID-19 waves in Victoria, Australia. We find that our approach offers high resolution, cluster-specific serial interval estimates that are comparable with those obtained from contact data, despite requiring no knowledge of who infected whom and relying on incompletely-sampled data. Compared to a published serial interval, cluster-specific serial intervals can vary estimates of the effective reproduction number by a factor of 2–3. We find that serial interval estimates in settings such as schools and meat processing/packing plants are shorter than those in healthcare facilities.

[Infection, Genetics and Evolution, 2 August 2023]

Objectives: Clustering pathogen sequence data is a common practice in epidemiology to gain insights into the genetic diversity and evolutionary relationships among pathogens. We can find groups of cases with a shared transmission history and common origin, as well as identifying transmission hotspots. Motivated by the experience of clustering SARS-CoV-2 cases using whole genome sequence data during the COVID-19 pandemic to aid with public health investigation, we investigated how differences in epidemiology and sampling can influence the composition of clusters that are identified.

Methods: We performed genomic clustering on simulated SARS-CoV-2 outbreaks produced with different transmission rates and levels of genomic diversity, along with varying the proportion of cases sampled.

Results: In single outbreaks with a low transmission rate, decreasing the sampling fraction resulted in multiple, separate clusters being identified where intermediate cases in transmission chains are missed. Outbreaks simulated with a high transmission rate were more robust to changes in the sampling fraction and largely resulted in a single cluster that included all sampled outbreak cases. When considering multiple outbreaks in a sampled jurisdiction seeded by different introductions, low genomic diversity between introduced cases caused outbreaks to be merged into large clusters. If the transmission and sampling fraction, and diversity between introductions was low, a combination of the spurious break-up of outbreaks and the linking of closely related cases in different outbreaks resulted in clusters that may appear informative, but these did not reflect the true underlying population structure. Conversely, genomic clusters matched the true population structure when there was relatively high diversity between introductions and a high transmission rate.

Conclusion: Differences in epidemiology and sampling can impact our ability to identify genomic clusters that describe the underlying population structure. These findings can help to guide recommendations for the use of pathogen clustering in public health investigations.

[Genome Research, 22 May 2023]

The reconstruction of phylogenetic networks is an important but challenging problem in phylogenetics and genome evolution, as the space of phylogenetic networks is vast and cannot be sampled well. One approach to the problem is to solve the minimum phylogenetic network problem, in which phylogenetic trees are first inferred, and then the smallest phylogenetic network that displays all the trees is computed. The approach takes advantage of the fact that the theory of phylogenetic trees is mature, and there are excellent tools available for inferring phylogenetic trees from a large number of biomolecular sequences. A tree–child network is a phylogenetic network satisfying the condition that every nonleaf node has at least one child that is of indegree one. Here, we develop a new method that infers the minimum tree–child network by aligning lineage taxon strings in the phylogenetic trees. This algorithmic innovation enables us to get around the limitations of the existing programs for phylogenetic network inference. Our new program, named ALTS, is fast enough to infer a tree–child network with a large number of reticulations for a set of up to 50 phylogenetic trees with 50 taxa that have only trivial common clusters in about a quarter of an hour on average.

[medRxiv, 10 June 2023]

Background: Vaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, associations between vaccine homophily, self-reported vaccination, COVID-19 prevention behaviours, contact network size, and self-reported COVID-19, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy.

Methods: Residents of British Columbia, Canada, aged ≥16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy.

Results: Vaccine homophily was observed among the 1304 respondents, but was lower among those with fewer doses (p<0.0001). Unvaccinated individuals had larger contact networks (p<0.0001), were more likely to report prior COVID-19 (p<0.0001), and reported lower compliance with COVID-19 prevention guidelines (p<0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Further, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as elevated force of infection from unvaccinated to vaccinated individuals under conditions of low vaccine efficacy.

Interpretation: The uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

Citerank: (11) 679814Jonathan DushoffProfessor in the Department Of Biology at McMaster University.10019D3ABAB, 679875Sarah OttoProfessor in Zoology. Theoretical biologist, Canada Research Chair in Theoretical and Experimental Evolution, and Killam Professor at the University of British Columbia.10019D3ABAB, 685445Michael WZ LiMichael Li is Senior Scientist in the Public Health Risk Science Division (PHRS) of the Public Health Agency of Canada (PHAC) and a Research Associate at the South African Centre for Epidemiological Modelling and Analysis (SACEMA).10019D3ABAB, 701020CANMOD – PublicationsPublications by CANMOD Members144B5ACA0, 701023GenomicsWhile virus genomes can describe the global context of introductions and origins of local clusters of cases, CANMOD will focus on building methods for characterizing and modelling local transmission once it is established, and for surveillance for viral determinants of increased fitness and of enhanced risk of spillover, virulence and transmission.859FDEF6, 701037MfPH – Publications144B5ACA0, 704045Covid-19859FDEF6, 707634Gary Van DomselaarDr. Gary Van Domselaar, PhD (University of Alberta, 2003) is the Chief of the Bioinformatics Laboratory at the National Microbiology Laboratory in Winnipeg Canada, and Adjunct Professor in the Department of Medical Microbiology at the University of Manitoba.10019D3ABAB, 708734Genomics859FDEF6, 715277Covid-19Covid-19 » Relevance » Genomics10000FFFACD, 715329Nick OgdenNicholas Ogden is a senior research scientist and Director of the Public Health Risk Sciences Division within the National Microbiology Laboratory at the Public Health Agency of Canada.10019D3ABAB

[Canada Communicable Disease Report, 6 April 2022]

Genomic surveillance during the coronavirus disease 2019 (COVID-19) pandemic has been key to the timely identification of virus variants with important public health consequences, such as variants that can transmit among and cause severe disease in both vaccinated or recovered individuals. The rapid emergence of the Omicron variant highlighted the speed with which the extent of a threat must be assessed. Rapid sequencing and public health institutions’ openness to sharing sequence data internationally give an unprecedented opportunity to do this; however, assessing the epidemiological and clinical properties of any new variant remains challenging. Here we highlight a “band of four” key data sources that can help to detect viral variants that threaten COVID-19 management: 1) genetic (virus sequence) data; 2) epidemiological and geographic data; 3) clinical and demographic data; and 4) immunization data. We emphasize the benefits that can be achieved by linking data from these sources and by combining data from these sources with virus sequence data. The considerable challenges of making genomic data available and linked with virus and patient attributes must be balanced against major consequences of not doing so, especially if new variants of concern emerge and spread without timely detection and action.

Citerank: (22) 679703EIDM?The Emerging Infectious Diseases Modelling Initiative (EIDM) – by the Public Health Agency of Canada and NSERC – aims to establish multi-disciplinary network(s) of specialists across the country in modelling infectious diseases to be applied to public needs associated with emerging infectious diseases and pandemics such as COVID-19. [1]7F1CEB7, 679769Christopher CottonChristopher Cotton is a Professor of Economics at Queen’s University where he holds the Jarislowsky-Deutsch Chair in Economic & Financial Policy.10019D3ABAB, 679776David EarnProfessor of Mathematics and Faculty of Science Research Chair in Mathematical Epidemiology at McMaster University.10019D3ABAB, 679797Huaiping ZhuProfessor of mathematics at the Department of Mathematics and Statistics at York University, a York Research Chair (YRC Tier I) in Applied Mathematics, the Director of the Laboratory of Mathematical Parallel Systems at the York University (LAMPS), the Director of the Canadian Centre for Diseases Modelling (CCDM) and the Director of the One Health Modelling Network for Emerging Infections (OMNI-RÉUNIS). 10019D3ABAB, 679806Jane HeffernanJane Heffernan is a professor of infectious disease modelling in the Mathematics & Statistics Department at York University. She is a co-director of the Canadian Centre for Disease Modelling, and she leads national and international networks in mathematical immunology and the modelling of waning and boosting immunity.10019D3ABAB, 679812Jianhong WuProfessor Jianhong Wu is a University Distinguished Research Professor and Senior Canada Research Chair in industrial and applied mathematics at York University. He is also the NSERC Industrial Research Chair in vaccine mathematics, modelling, and manufacturing. 10019D3ABAB, 679826Laura CowenAssociate Professor in the Department of Mathematics and Statistics at the University of Victoria.10019D3ABAB, 679842Mark LewisProfessor Mark Lewis, Kennedy Chair in Mathematical Biology at the University of Victoria and Emeritus Professor at the University of Alberta.10019D3ABAB, 679858Patrick BrownAssociate Professor in the Centre for Global Health Research at St. Michael’s Hospital, and in the Department of Statistical Sciences at the University of Toronto.10019D3ABAB, 679859Patrick LeightonPatrick Leighton is a Professor of Epidemiology and Public Health at the Faculty of Veterinary Medicine, University of Montreal, and an active member of the Epidemiology of Zoonoses and Public Health Research Group (GREZOSP) and the Centre for Public Health Research (CReSP). 10019D3ABAB, 679869Rob DeardonAssociate Professor in the Department of Production Animal Health in the Faculty of Veterinary Medicine and the Department of Mathematics and Statistics in the Faculty of Science at the University of Calgary.10019D3ABAB, 679875Sarah OttoProfessor in Zoology. Theoretical biologist, Canada Research Chair in Theoretical and Experimental Evolution, and Killam Professor at the University of British Columbia.10019D3ABAB, 679890Troy DayTroy Day is a Professor and the Associate Head of the Department of Mathematics and Statistics at Queen’s University. He is an applied mathematician whose research focuses on dynamical systems, optimization, and game theory, applied to models of infectious disease dynamics and evolutionary biology.10019D3ABAB, 679893Kumar MurtyProfessor Kumar Murty is in the Department of Mathematics at the University of Toronto. His research fields are Analytic Number Theory, Algebraic Number Theory, Arithmetic Algebraic Geometry and Information Security. He is the founder of the GANITA lab, co-founder of Prata Technologies and PerfectCloud. His interest in mathematics ranges from the pure study of the subject to its applications in data and information security.10019D3ABAB, 686724Ellen RaffertyDr. Ellen Rafferty has a Master of Public Health and a PhD in epidemiology and health economics from the University of Saskatchewan. Dr. Rafferty’s research focuses on the epidemiologic and economic impact of public health policies, such as estimating the cost-effectiveness of immunization programs. She is interested in the incorporation of economics into immunization decision-making, and to that aim has worked with a variety of provincial and national organizations.10019D3ABAB, 701020CANMOD – PublicationsPublications by CANMOD Members144B5ACA0, 701037MfPH – Publications144B5ACA0, 701071OSN – Publications144B5ACA0, 701222OMNI – Publications144B5ACA0, 704045Covid-19859FDEF6, 714608Charting a FutureCharting a Future for Emerging Infectious Disease Modelling in Canada – April 2023 [1] 2794CAE1, 715387SMMEID – Publications144B5ACA0

We propose an independent institute of emerging infectious disease modellers and policy experts, with an academic core, capable of renewing itself as needed. This institute will combine science and knowledge translation to inform decision-makers at all levels of government and ensure the highest level of preparedness (and readiness) for the next public health emergency. The Public Health Modelling Institute will provide cost-effective, science-based modelling for public policymakers in an easily visualizable, integrated framework, which can respond in an agile manner to changing needs, questions, and data. To be effective, the Institute must link to modelling groups within government, who are best able to pose questions and convey results for use by public policymakers.

Under the implementation of non-pharmaceutical interventions such as social distancing and lockdowns, household transmission has been shown to be significant for COVID-19, posing challenges for reducing incidence in settings where people are asked to self-isolate at home and to spend increasing amounts of time at home due to distancing measures. Accordingly, characteristics of households in a region have been shown to relate to transmission heterogeneity of the virus. We introduce a stochastic epidemiological model to examine the impact of the household size distribution in a region on the transmission dynamics. We choose parameters to reflect incidence in two health regions of the Greater Vancouver area in British Columbia and simulate the impact of distancing measures on transmission, with household size distribution the only different parameter between simulations for the two regions. Our result suggests that the dissimilarity in household size distribution alone can cause significant differences in incidence of the two regions, and the distributions drive distinct dynamics that match reported cases. Furthermore, our model suggests that offering individuals a place to isolate outside their household can speed the decline in cases, and does so more effectively where there are more larger households.

[medRxiv, 29 September 2023]

COVID-19 has become endemic, with dynamics that reflect the waning of immunity and re-exposure, by contrast to the epidemic phase driven by exposure in immunologically naïve populations. Endemic does not, however, mean constant. Further evolution of SARS-CoV-2, as well as changes in behaviour and public health policy, continue to play a major role in the endemic load of disease and mortality. In this paper, we analyse evolutionary models to explore the impact that newly arising variants can have on the short-term and longer-term endemic load, characterizing how these impacts depend on the transmission and immunological properties of variants. We describe how evolutionary changes in the virus will increase the endemic load most for persistently immune-escape variants, by an intermediate amount for more transmissible variants, and least for transiently immune-escape variants. Balancing the tendency for evolution to favour variants that increase the endemic load, we explore the impact of vaccination strategies and non-pharmaceutical interventions (NPIs) that can counter these increases in the impact of disease. We end with some open questions about the future of COVID-19 as an endemic disease.

Citerank: (11) 679770Christopher McCabeDr. Christopher McCabe is the CEO and Executive Director of the Institute of Health Economics (IHE).10019D3ABAB, 679862Paul TupperProfessor in the Department of Mathematics at Simon Fraser University.10019D3ABAB, 685420Hospitals16289D5D4, 686720Erin KirwinErin Kirwin (she/her) is a Health Economist at the Institute of Health Economics (IHE) in Alberta, Canada. She holds a Bachelor of Arts (Honours) in Economics and International Development Studies from McGill University and a Master of Arts in Economics from the University of Alberta. Prior to joining the IHE, Erin was the Manager of Advanced Analytics at Alberta Health. Erin is a PhD candidate at the University of Manchester.10019D3ABAB, 701020CANMOD – PublicationsPublications by CANMOD Members144B5ACA0, 704041Vaccination859FDEF6, 704045Covid-19859FDEF6, 708794Health economics859FDEF6, 714608Charting a FutureCharting a Future for Emerging Infectious Disease Modelling in Canada – April 2023 [1] 2794CAE1, 715454Workforce impact859FDEF6, 715952Long covid859FDEF6

[PLOS Global Public Health, 13 October 2021]

In vaccination campaigns against COVID-19, many jurisdictions are using age-based rollout strategies, reflecting the much higher risk of severe outcomes of infection in older groups. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection, we show that such strategies are less effective than strategies that prioritize essential workers. This conclusion holds across numerous outcomes, including cases, hospitalizations, Long COVID (cases with symptoms lasting longer than 28 days), deaths and net monetary benefit. Our analysis holds in regions where the vaccine supply is limited, and rollout is prolonged for several months. In such a setting with a population of 5M, we estimate that vaccinating essential workers sooner prevents over 200,000 infections, over 600 deaths, and produces a net monetary benefit of over $500M.

[Epidemics, 6 December 2023]

The serial interval of an infectious disease is an important variable in epidemiology. It is defined as the period of time between the symptom onset times of the infector and infectee in a direct transmission pair. Under partially sampled data, purported infector–infectee pairs may actually be separated by one or more unsampled cases in between. Misunderstanding such pairs as direct transmissions will result in overestimating the length of serial intervals. On the other hand, two cases that are infected by an unseen third case (known as coprimary transmission) may be classified as a direct transmission pair, leading to an underestimation of the serial interval. Here, we introduce a method to jointly estimate the distribution of serial intervals factoring in these two sources of error. We simultaneously estimate the distribution of the number of unsampled intermediate cases between purported infector–infectee pairs, as well as the fraction of such pairs that are coprimary. We also extend our method to situations where each infectee has multiple possible infectors, and show how to factor this additional source of uncertainty into our estimates. We assess our method’s performance on simulated data sets and find that our method provides consistent and robust estimates. We also apply our method to data from real-life outbreaks of four infectious diseases and compare our results with published results. With similar accuracy, our method of estimating serial interval distribution provides unique advantages, allowing its application in settings of low sampling rates and large population sizes, such as widespread community transmission tracked by routine public health surveillance.

[PLoS Computational Biology, 28 December 2023]

The mechanisms behind vaccine-induced strain replacement in the pneumococcus remain poorly understood. There is emerging evidence that distinct pneumococcal lineages can co-colonise for significant time periods, and that novel recombinants can readily emerge during natural colonisation. Despite this, patterns of post-vaccine replacement are indicative of competition between specific lineages. Here, we develop a multiscale transmission model to investigate explicitly how within host dynamics shape observed ecological patterns, both pre- and post-vaccination. Our model framework explores competition between and within strains defined by distinct antigenic, metabolic and resistance profiles. We allow for strains to freely co-colonise and recombine within hosts, and consider how each of these types may contribute to a strain’s overall fitness. Our results suggest that antigenic and resistance profiles are key drivers of post-vaccine success.

[Journal of Theoretical Biology, 8 December 2023]

We investigated the implications of employing a circular approximation of split systems in the calculation of maximum diversity subsets of a set of taxa in a conservation biology context where diversity is measured using Split System Diversity (SSD). We conducted a comparative analysis between the maximum SSD score and the maximum SSD set(s) of size k, efficiently determined using a circular approximation, and the true results obtained through brute-force search based on the original data. Through experimentation on simulated datasets and SNP data across 50 Atlantic Salmon populations, our findings demonstrate that employing a circular approximation can lead to the generation of an incorrect max-SSD set(s). We built a graph-based split system whose circular approximation led to a max-SSD set of size k=4 that was less than the true max-SSD set by 17.6%. This discrepancy increased to 25% for k=11 when we used a hypergraph-based split system. The same comparison on the Atlantic salmon dataset revealed a mere 1% difference. However, noteworthy disparities emerged in the population composition between the two sets. These findings underscore the importance of assessing the suitability of circular approximations in conservation biology systems. Caution is advised when relying solely on circular approximations to determine sets of maximum diversity, and careful consideration of the data characteristics is crucial for accurate results in conservation biology applications.

[Mathematics of Public Health, 7 August 2023]

The continuous emergence and spread of new variants of SARS-CoV-2 has added an extra layer of complexity in the effort to effectively control the pandemic. The long-term impact of the new variants, and how they will interplay with population immunity and other factors to shape future resurgence of infection, is not fully understood. To provide some insight on this, we simulate future SARS-CoV-2 variants assuming Poisson process arrival times in British Columbia, Canada, sampling their transmissibility and immune escape capacity from a multivariate log-normal distribution. Using a two-strain deterministic model that incorporates waning of immunity and breakthrough infection, we explore the long-term dynamics of COVID-19 in British Columbia. Our model predicts multiple waves of resurgence of SARS-CoV-2 infection modulated by transmissibility, immune escape capacity and variants’ arrival rates, without achieving stable endemicity within the next 3 years. The peak and rate of resurgence of infection waves can be reduced by continuous boosting of immunity with efficacious vaccines, while proactive measures are employed to encourage booster uptake.

[Evolution, 1 June 2024]

COVID-19 has become endemic, with dynamics that reflect the waning of immunity and re-exposure, by contrast to the epidemic phase driven by exposure in immunologically naïve populations. Endemic does not, however, mean constant. Further evolution of SARS-CoV-2, as well as changes in behavior and public health policy, continue to play a major role in the endemic load of disease and mortality. In this article, we analyze evolutionary models to explore the impact that a newly arising variant can have on the short-term and longer-term endemic load, characterizing how these impacts depend on the transmission and immunological properties of the variants. We describe how evolutionary changes in the virus will increase the endemic load most for a persistently immune-escape variant, by an intermediate amount for a more transmissible variant, and least for a transiently immune-escape variant. Balancing the tendency for evolution to favor variants that increase the endemic load, we explore the impact of vaccination strategies and non-pharmaceutical interventions that can counter these increases in the impact of disease. We end with some open questions about the future of COVID-19 as an endemic disease.

[bioRxiv, 15 July 2024]

We introduce and apply Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories (BREATH), a method to simultaneously construct phylogenetic trees and transmission trees using sequence data for a person-to-person outbreak. BREATH’s transmission process that accounts for a flexible natural history of infection (including a latent period if desired) and a separate process for sampling. It allows for unsampled individuals and for individuals to have diverse within-host infections. BREATH also accounts for the fact that an outbreak may still be ongoing at the time of analysis, using a recurrent events approach to account for right truncation. We perform a simulation study to verify our implementation, and apply BREATH to a previously-described 13-year outbreak of tuber-culosis. We find that using a transmission process to inform the phylogenetic reconstruction results in better resolution of the phylogeny (in topology, branch length and tree height) and a more precise estimate of the time of origin of the outbreak. Considerable uncertainty remains about transmission events in the outbreak, but our reconstructed transmission network resolves two major waves of transmission consistent with the previously-described epidemiology, estimates the numbers of unsampled individuals, and describes some highprobability transmission pairs.

An open source implementation of BREATH is available from:

https://github.com/rbo...

…as the BREATH package to BEAST 2.