The response of Canada's clinical health research ecosystem to the COVID-19 pandemic.

BACKGROUND: The response of Canada's research community to the COVID-19 pandemic provides a unique opportunity to examine the country's clinical health research ecosystem. We sought to describe patterns of enrolment across Canadian Institutes of Health Research (CIHR)-funded studies on COVID-19. METHODS: We identified COVID-19 studies funded by the CIHR and that enrolled participants from Canadian acute care hospitals between January 2020 and April 2023. We collected information on study-and site-level variables from study leads, site investigators, and public domain sources. We described and evaluated factors associated with cumulative enrolment. RESULTS: We obtained information for 23 out of 26 (88%) eligible CIHR-funded studies (16 randomized controlled trials [RCTs] and 7 cohort studies). The 23 studies were managed by 12 Canadian and 3 international coordinating centres. Of 419 Canadian hospitals, 97 (23%) enrolled a total of 28 973 participants - 3876 in RCTs across 78 hospitals (median cumulative enrolment per hospital 30, interquartile range [IQR] 10-61), and 25 097 in cohort studies across 62 hospitals (median cumulative enrolment per hospital 158, IQR 6-348). Of 78 hospitals recruiting participants in RCTs, 13 (17%) enrolled 50% of all RCT participants, whereas 6 of 62 hospitals (9.7%) recruited 54% of participants in cohort studies. INTERPRETATION: A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and provides information for multiple key partners to consider ways to realize the full research potential of Canada's health systems.

Compressing the Chronology of a Temporal Network with Graph Commutators.

Studies of dynamics on temporal networks often represent the network as a series of "snapshots," static networks active for short durations of time. We argue that successive snapshots can be aggregated if doing so has little effect on the overlying dynamics. We propose a method to compress network chronologies by progressively combining pairs of snapshots whose matrix commutators have the smallest dynamical effect. We apply this method to epidemic modeling on real contact tracing data and find that it allows for significant compression while remaining faithful to the epidemic dynamics.

Temporal and probabilistic comparisons of epidemic interventions.

Forecasting disease spread is a critical tool to help public health officials design and plan public health interventions.However, the expected future state of an epidemic is not necessarily well defined as disease spread is inherently stochastic, contact patterns within a population are heterogeneous, and behaviors change. In this work, we use time-dependent probability generating functions (PGFs) to capture these characteristics by modeling a stochastic branching process of the spread of a disease over a network of contacts in which public health interventions are introduced over time. To achieve this, we define a general transmissibility equation to account for varying transmission rates (e.g. masking), recovery rates (e.g. treatment), contact patterns (e.g. social distancing) and percentage of the population immunized (e.g. vaccination). The resulting framework allows for a temporal and probabilistic analysis of an intervention's impact on disease spread, which match continuous-time stochastic simulations that are much more computationally expensive.To aid policy making, we then define several metrics over which temporal and probabilistic intervention forecasts can be compared: Looking at the expected number of cases and the worst-case scenario over time, as well as the probability of reaching a critical level of cases and of not seeing any improvement following an intervention.Given that epidemics do not always follow their average expected trajectories and that the underlying dynamics can change over time, our work paves the way for more detailed short-term forecasts of disease spread and more informed comparison of intervention strategies.

Nonlinear bias toward complex contagion in uncertain transmission settings.

Current epidemics in the biological and social domains are challenging the standard assumptions of mathematical contagion models. Chief among them are the complex patterns of transmission caused by heterogeneous group sizes and infection risk varying by orders of magnitude in different settings, like indoor versus outdoor gatherings in the COVID-19 pandemic or different moderation practices in social media communities. However, quantifying these heterogeneous levels of risk is difficult, and most models typically ignore them. Here, we include these features in an epidemic model on weighted hypergraphs to capture group-specific transmission rates. We study analytically the consequences of ignoring the heterogeneous transmissibility and find an induced superlinear infection rate during the emergence of a new outbreak, even though the underlying mechanism is a simple, linear contagion. The dynamics produced at the individual and group levels are therefore more similar to complex, nonlinear contagions, thus blurring the line between simple and complex contagions in realistic settings. We support this claim by introducing a Bayesian inference framework to quantify the nonlinearity of contagion processes. We show that simple contagions on real weighted hypergraphs are systematically biased toward the superlinear regime if the heterogeneity of the weights is ignored, greatly increasing the risk of erroneous classification as complex contagions. Our results provide an important cautionary tale for the challenging task of inferring transmission mechanisms from incidence data. Yet, it also paves the way for effective models that capture complex features of epidemics through nonlinear infection rates.

Network analysis of patterns and relevance of enteric pathogen co-infections among infants in a diarrhea-endemic setting.

Despite significant progress in recent decades toward ameliorating the excess burden of diarrheal disease globally, childhood diarrhea remains a leading cause of morbidity and mortality in low-and-middle-income countries (LMICs). Recent large-scale studies of diarrhea etiology in these populations have revealed widespread co-infection with multiple enteric pathogens, in both acute and asymptomatic stool specimens. We applied methods from network science and ecology to better understand the underlying structure of enteric co-infection among infants in two large longitudinal birth cohorts in Bangladesh. We used a configuration model to establish distributions of expected random co-occurrence, based on individual pathogen prevalence alone, for every pathogen pair among 30 enteropathogens detected by qRT-PCR in both diarrheal and asymptomatic stool specimens. We found two pairs, Enterotoxigenic E. coli (ETEC) with Enteropathogenic E. coli (EPEC), and ETEC with Campylobacter spp., co-infected significantly more than expected at random (both pairs co-occurring almost 4 standard deviations above what one could expect due to chance alone). Furthermore, we found a general pattern that bacteria-bacteria pairs appear together more frequently than expected at random, while virus-bacteria pairs tend to appear less frequently than expected based on model predictions. Finally, infants co-infected with leading bacteria-bacteria pairs had more days of diarrhea in the first year of life compared to infants without co-infection (p-value <0.0001). Our methods and results help us understand the structure of enteric co-infection which can guide further work to identify and eliminate common sources of infection or determine biologic mechanisms that promote co-infection.

Temporal and Probabilistic Comparisons of Epidemic Interventions.

Forecasting disease spread is a critical tool to help public health officials design and plan public health interventions. However, the expected future state of an epidemic is not necessarily well defined as disease spread is inherently stochastic, contact patterns within a population are heterogeneous, and behaviors change. In this work, we use time-dependent probability generating functions (PGFs) to capture these characteristics by modeling a stochastic branching process of the spread of a disease over a network of contacts in which public health interventions are introduced over time. To achieve this, we define a general transmissibility equation to account for varying transmission rates (e.g. masking), recovery rates (e.g. treatment), contact patterns (e.g. social distancing) and percentage of the population immunized (e.g. vaccination). The resulting framework allows for a temporal and probabilistic analysis of an intervention's impact on disease spread, which match continuous-time stochastic simulations that are much more computationally expensive. To aid policy making, we then define several metrics over which temporal and probabilistic intervention forecasts can be compared: Looking at the expected number of cases and the worst-case scenario over time, as well as the probability of reaching a critical level of cases and of not seeing any improvement following an intervention. Given that epidemics do not always follow their average expected trajectories and that the underlying dynamics can change over time, our work paves the way for more detailed short-term forecasts of disease spread and more informed comparison of intervention strategies.

Operationalizing cultural adaptation to climate change: contemporary examples from United States agriculture.

It has been proposed that climate adaptation research can benefit from an evolutionary approach. But related empirical research is lacking. We advance the evolutionary study of climate adaptation with two case studies from contemporary United States agriculture. First, we define 'cultural adaptation to climate change' as a mechanistic process of population-level cultural change. We argue this definition enables rigorous comparisons, yields testable hypotheses from mathematical theory and distinguishes adaptive change, non-adaptive change and desirable policy outcomes. Next, we develop an operational approach to identify 'cultural adaptation to climate change' based on established empirical criteria. We apply this approach to data on crop choices and the use of cover crops between 2008 and 2021 from the United States. We find evidence that crop choices are adapting to local trends in two separate climate variables in some regions of the USA. But evidence suggests that cover cropping may be adapting more to the economic environment than climatic conditions. Further research is needed to characterize the process of cultural adaptation, particularly the routes and mechanisms of cultural transmission. Furthermore, climate adaptation policy could benefit from research on factors that differentiate regions exhibiting adaptive trends in crop choice from those that do not. This article is part of the theme issue 'Climate change adaptation needs a science of culture'.

Accurately summarizing an outbreak using epidemiological models takes time.

Recent outbreaks of Mpox and Ebola, and worrying waves of COVID-19, influenza and respiratory syncytial virus, have all led to a sharp increase in the use of epidemiological models to estimate key epidemiological parameters. The feasibility of this estimation task is known as the practical identifiability (PI) problem. Here, we investigate the PI of eight commonly reported statistics of the classic susceptible-infectious-recovered model using a new measure that shows how much a researcher can expect to learn in a model-based Bayesian analysis of prevalence data. Our findings show that the basic reproductive number and final outbreak size are often poorly identified, with learning exceeding that of individual model parameters only in the early stages of an outbreak. The peak intensity, peak timing and initial growth rate are better identified, being in expectation over 20 times more probable having seen the data by the time the underlying outbreak peaks. We then test PI for a variety of true parameter combinations and find that PI is especially problematic in slow-growing or less-severe outbreaks. These results add to the growing body of literature questioning the reliability of inferences from epidemiological models when limited data are available.

Multidisciplinary learning through collective performance favors decentralization.

Many models of learning in teams assume that team members can share solutions or learn concurrently. However, these assumptions break down in multidisciplinary teams where team members often complete distinct, interrelated pieces of larger tasks. Such contexts make it difficult for individuals to separate the performance effects of their own actions from the actions of interacting neighbors. In this work, we show that individuals can overcome this challenge by learning from network neighbors through mediating artifacts (like collective performance assessments). When neighbors' actions influence collective outcomes, teams with different networks perform relatively similarly to one another. However, varying a team's network can affect performance on tasks that weight individuals' contributions by network properties. Consequently, when individuals innovate (through "exploring" searches), dense networks hurt performance slightly by increasing uncertainty. In contrast, dense networks moderately help performance when individuals refine their work (through "exploiting" searches) by efficiently finding local optima. We also find that decentralization improves team performance across a battery of 34 tasks. Our results offer design principles for multidisciplinary teams within which other forms of learning prove more difficult.

TRACE-Omicron: Policy Counterfactuals to Inform Mitigation of COVID-19 Spread in the United States.

The Omicron wave was the largest wave of COVID-19 pandemic to date, more than doubling any other in terms of cases and hospitalizations in the United States. In this paper, we present a large-scale agent-based model of policy interventions that could have been implemented to mitigate the Omicron wave. Our model takes into account the behaviors of individuals and their interactions with one another within a nationally representative population, as well as the efficacy of various interventions such as social distancing, mask wearing, testing, tracing, and vaccination. We use the model to simulate the impact of different policy scenarios and evaluate their potential effectiveness in controlling the spread of the virus. Our results suggest the Omicron wave could have been substantially curtailed via a combination of interventions comparable in effectiveness to extreme and unpopular singular measures such as widespread closure of schools and workplaces, and highlight the importance of early and decisive action.

The unintended consequences of inconsistent closure policies and mobility restrictions during epidemics.

Background: Controlling the spread of infectious diseases-even when safe, transmission-blocking vaccines are available-may require the effective use of non-pharmaceutical interventions (NPIs), e.g., mask wearing, testing, limits on group sizes, venue closure. During the SARS-CoV-2 pandemic, many countries implemented NPIs inconsistently in space and time. This inconsistency was especially pronounced for policies in the United States of America (US) related to venue closure. Methods: Here, we investigate the impact of inconsistent policies associated with venue closure using mathematical modeling and high-resolution human mobility, Google search, and county-level SARS-CoV-2 incidence data from the USA. Specifically, we look at high-resolution location data and perform a US-county-level analysis of nearly 8 million SARS-CoV-2 cases and 150 million location visits, including 120 million church visitors across 184,677 churches, 14 million grocery visitors across 7662 grocery stores, and 13.5 million gym visitors across 5483 gyms. Results: Analyzing the interaction between venue closure and changing mobility using a mathematical model shows that, across a broad range of model parameters, inconsistent or partial closure can be worse in terms of disease transmission as compared to scenarios with no closures at all. Importantly, changes in mobility patterns due to epidemic control measures can lead to increase in the future number of cases. In the most severe cases, individuals traveling to neighboring jurisdictions with different closure policies can result in an outbreak that would otherwise have been contained. To motivate our mathematical models, we turn to mobility data and find that while stay-at-home orders and closures decreased contacts in most areas of the USA, some specific activities and venues saw an increase in attendance and an increase in the distance visitors traveled to attend. We support this finding using search query data, which clearly shows a shift in information seeking behavior concurrent with the changing mobility patterns. Conclusions: While coarse-grained observations are not sufficient to validate our models, taken together, they highlight the potential unintended consequences of inconsistent epidemic control policies related to venue closure and stress the importance of balancing the societal needs of a population with the risk of an outbreak growing into a large epidemic. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-023-00028-z.

Immunity-induced criticality of the genotype network of influenza A (H3N2) hemagglutinin.

Seasonal influenza kills hundreds of thousands every year, with multiple constantly changing strains in circulation at any given time. A high mutation rate enables the influenza virus to evade recognition by the human immune system, including immunity acquired through past infection and vaccination. Here, we capture the genetic similarity of influenza strains and their evolutionary dynamics with genotype networks. We show that the genotype networks of influenza A (H3N2) hemagglutinin are characterized by heavy-tailed distributions of module sizes and connectivity indicative of critical behavior. We argue that (i) genotype networks are driven by mutation and host immunity to explore a subspace of networks predictable in structure and (ii) genotype networks provide an underlying structure necessary to capture the rich dynamics of multistrain epidemic models. In particular, inclusion of strain-transcending immunity in epidemic models is dependent upon the structure of an underlying genotype network. This interplay is consistent with self-organized criticality where the epidemic dynamics of influenza locates critical regions of its genotype network. We conclude that this interplay between disease dynamics and network structure might be key for future network analysis of pathogen evolution and realistic multistrain epidemic models.

Spatial epidemiology and adaptive targeted sampling to manage the Chagas disease vector Triatoma dimidiata.

Widespread application of insecticide remains the primary form of control for Chagas disease in Central America, despite only temporarily reducing domestic levels of the endemic vector Triatoma dimidiata and having little long-term impact. Recently, an approach emphasizing community feedback and housing improvements has been shown to yield lasting results. However, the additional resources and personnel required by such an intervention likely hinders its widespread adoption. One solution to this problem would be to target only a subset of houses in a community while still eliminating enough infestations to interrupt disease transfer. Here we develop a sequential sampling framework that adapts to information specific to a community as more houses are visited, thereby allowing us to efficiently find homes with domiciliary vectors while minimizing sampling bias. The method fits Bayesian geostatistical models to make spatially informed predictions, while gradually transitioning from prioritizing houses based on prediction uncertainty to targeting houses with a high risk of infestation. A key feature of the method is the use of a single exploration parameter, α, to control the rate of transition between these two design targets. In a simulation study using empirical data from five villages in southeastern Guatemala, we test our method using a range of values for α, and find it can consistently select fewer homes than random sampling, while still bringing the village infestation rate below a given threshold. We further find that when additional socioeconomic information is available, much larger savings are possible, but that meeting the target infestation rate is less consistent, particularly among the less exploratory strategies. Our results suggest new options for implementing long-term T. dimidiata control.

Source-sink behavioural dynamics limit institutional evolution in a group-structured society.

Social change in any society entails changes in both behaviours and institutions. We model a group-structured society in which the transmission of individual behaviour occurs in parallel with the selection of group-level institutions. We consider a cooperative behaviour that generates collective benefits for groups but does not spread between individuals on its own. Groups exhibit institutions that increase the diffusion of the behaviour within the group, but also incur a group cost. Groups adopt institutions in proportion to their fitness. Finally, the behaviour may also spread globally. We find that behaviour and institutions can be mutually reinforcing. But the model also generates behavioural source-sink dynamics when behaviour generated in institutionalized groups spreads to non-institutionalized groups and boosts their fitness. Consequently, the global diffusion of group-beneficial behaviour creates a pattern of institutional free-riding that limits the evolution of group-beneficial institutions. Our model suggests that, in a group-structured society, large-scale beneficial social change can be best achieved when the relevant behaviour and institutions remain correlated.

The role of directionality, heterogeneity and correlations in epidemic risk and spread.

Most models of epidemic spread, including many designed specifically for COVID-19, implicitly assume mass-action contact patterns and undirected contact networks, meaning that the individuals most likely to spread the disease are also the most at risk to receive it from others. Here, we review results from the theory of random directed graphs which show that many important quantities, including the reproduction number and the epidemic size, depend sensitively on the joint distribution of in- and out-degrees ("risk" and "spread"), including their heterogeneity and the correlation between them. By considering joint distributions of various kinds, we elucidate why some types of heterogeneity cause a deviation from the standard Kermack-McKendrick analysis of SIR models, i.e., so-called mass-action models where contacts are homogeneous and random, and some do not. We also show that some structured SIR models informed by realistic complex contact patterns among types of individuals (age or activity) are simply mixtures of Poisson processes and tend not to deviate significantly from the simplest mass-action model. Finally, we point out some possible policy implications of this directed structure, both for contact tracing strategy and for interventions designed to prevent superspreading events. In particular, directed graphs have a forward and backward version of the classic "friendship paradox" -- forward edges tend to lead to individuals with high risk, while backward edges lead to individuals with high spread -- such that a combination of both forward and backward contact tracing is necessary to find superspreading events and prevent future cascades of infection.

Coordinated support for local action: Modeling strategies to facilitate behavior adoption in urban-poor communities of Liberia for sustained COVID-19 suppression.

BACKGROUND: Long-term suppression of SARS-CoV-2 transmission will involve strategies that recognize the heterogeneous capacity of communities to undertake public health recommendations. We highlight the epidemiological impact of barriers to adoption and the potential role of community-led coordination of support for cases and high-risk contacts in urban slums. METHODS: A compartmental model representing transmission of SARS-CoV-2 in urban poor versus less socioeconomically vulnerable subpopulations was developed for Montserrado County, Liberia. Adoption of home-isolation behavior was assumed to be related to the proportion of each subpopulation residing in housing units with multiple rooms and with access to sanitation, water, and food. We evaluated the potential impact of increasing the maximum attainable proportion of adoption among urban poor following the scheduled lifting of the state of emergency. RESULTS: Without intervention, the model estimated higher overall infection burden but fewer severe cases among urban poor versus the less socioeconomically vulnerable population. With self-isolation by mildly symptomatic individuals, median reductions in cumulative infections, severe cases, and maximum daily incidence were 7.6% (IQR: 2.2%-20.9%), 7.0% (2.0%-18.5%), and 9.9% (2.5%-31.4%), respectively, in the urban poor subpopulation and 16.8% (5.5%-29.3%), 15.0% (5.0%-26.4%), and 28.1% (9.3%-47.8%) in the less socioeconomically vulnerable population. An increase in the maximum attainable percentage of behavior adoption by the urban slum subpopulation was associated with median reductions of 19.2% (10.1%-34.0%), 21.1% (13.3%-34.2%), and 26.0% (11.5%-48.9%) relative to the status quo scenario. CONCLUSIONS: Post-lockdown recommendations that prioritize home-isolation by confirmed cases are limited by resource constraints. Investing in community-based initiatives that coordinate support for self-identified cases and their contacts could more effectively suppress COVID-19 in settings with socioeconomic vulnerabilities.

Universal Nonlinear Infection Kernel from Heterogeneous Exposure on Higher-Order Networks.

The collocation of individuals in different environments is an important prerequisite for exposure to infectious diseases on a social network. Standard epidemic models fail to capture the potential complexity of this scenario by (1) neglecting the higher-order structure of contacts that typically occur through environments like workplaces, restaurants, and households, and (2) assuming a linear relationship between the exposure to infected contacts and the risk of infection. Here, we leverage a hypergraph model to embrace the heterogeneity of environments and the heterogeneity of individual participation in these environments. We find that combining heterogeneous exposure with the concept of minimal infective dose induces a universal nonlinear relationship between infected contacts and infection risk. Under nonlinear infection kernels, conventional epidemic wisdom breaks down with the emergence of discontinuous transitions, superexponential spread, and hysteresis.

The effectiveness of backward contact tracing in networks.

Effective control of an epidemic relies on the rapid discovery and isolation of infected individuals. Because many infectious diseases spread through interaction, contact tracing is widely used to facilitate case discovery and control. However, what determines the efficacy of contact tracing has not been fully understood. Here we reveal that, compared with 'forward' tracing (tracing to whom disease spreads), 'backward' tracing (tracing from whom disease spreads) is profoundly more effective. The effectiveness of backward tracing is due to simple but overlooked biases arising from the heterogeneity in contacts. We argue that, even if the directionality of infection is unknown, it is possible to perform backward-aiming contact tracing. Using simulations on both synthetic and high-resolution empirical contact datasets, we show that strategically executed contact tracing can prevent a substantial fraction of transmissions with a higher efficiency-in terms of prevented cases per isolation-than case isolation alone. Our results call for a revision of current contact-tracing strategies so that they leverage all forms of bias. It is particularly crucial that we incorporate backward and deep tracing in a digital context while adhering to the privacy-preserving requirements of these new platforms.

Adaptive staffing can mitigate essential worker disease and absenteeism in an emerging epidemic.

Essential worker absenteeism has been a pressing problem in the COVID-19 pandemic. Nearly 20% of US hospitals experienced staff shortages, exhausting replacement pools and at times requiring COVID-positive healthcare workers to remain at work. To our knowledge there are no data-informed models examining how different staffing strategies affect epidemic dynamics on a network in the context of rising worker absenteeism. Here we develop a susceptible-infected-quarantined-recovered adaptive network model using pair approximations to gauge the effects of worker replacement versus redistribution of work among remaining healthy workers in the early epidemic phase. Parameterized with hospital data, the model exhibits a time-varying trade-off: Worker replacement minimizes peak prevalence in the early phase, while redistribution minimizes final outbreak size. Any "ideal" strategy requires balancing the need to maintain a baseline number of workers against the desire to decrease total number infected. We show that one adaptive strategy-switching from replacement to redistribution at epidemic peak-decreases disease burden by 9.7% and nearly doubles the final fraction of healthy workers compared to pure replacement.

A review and agenda for integrated disease models including social and behavioural factors.

Social and behavioural factors are critical to the emergence, spread and containment of human disease, and are key determinants of the course, duration and outcomes of disease outbreaks. Recent epidemics of Ebola in West Africa and coronavirus disease 2019 (COVID-19) globally have reinforced the importance of developing infectious disease models that better integrate social and behavioural dynamics and theories. Meanwhile, the growth in capacity, coordination and prioritization of social science research and of risk communication and community engagement (RCCE) practice within the current pandemic response provides an opportunity for collaboration among epidemiological modellers, social scientists and RCCE practitioners towards a mutually beneficial research and practice agenda. Here, we provide a review of the current modelling methodologies and describe the challenges and opportunities for integrating them with social science research and RCCE practice. Finally, we set out an agenda for advancing transdisciplinary collaboration for integrated disease modelling and for more robust policy and practice for reducing disease transmission.