The impact of long-term non-pharmaceutical interventions on COVID-19 epidemic dynamics and control: the value and limitations of early models.

Mathematical models of epidemics are important tools for predicting epidemic dynamics and evaluating interventions. Yet, because early models are built on limited information, it is unclear how long they will accurately capture epidemic dynamics. Using a stochastic SEIR model of COVID-19 fitted to reported deaths, we estimated transmission parameters at different time points during the first wave of the epidemic (March-June, 2020) in Santa Clara County, California. Although our estimated basic reproduction number ([Formula: see text]) remained stable from early April to late June (with an overall median of 3.76), our estimated effective reproduction number ([Formula: see text]) varied from 0.18 to 1.02 in April before stabilizing at 0.64 on 27 May. Between 22 April and 27 May, our model accurately predicted dynamics through June; however, the model did not predict rising summer cases after shelter-in-place orders were relaxed in June, which, in early July, was reflected in cases but not yet in deaths. While models are critical for informing intervention policy early in an epidemic, their performance will be limited as epidemic dynamics evolve. This paper is one of the first to evaluate the accuracy of an early epidemiological compartment model over time to understand the value and limitations of models during unfolding epidemics.

Evaluation of an open forecasting challenge to assess skill of West Nile virus neuroinvasive disease prediction.

BACKGROUND: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. METHODS: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. RESULTS: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. CONCLUSIONS: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases).

Not all mosquitoes are created equal: A synthesis of vector competence experiments reinforces virus associations of Australian mosquitoes.

The globalization of mosquito-borne arboviral diseases has placed more than half of the human population at risk. Understanding arbovirus ecology, including the role individual mosquito species play in virus transmission cycles, is critical for limiting disease. Canonical virus-vector groupings, such as Aedes- or Culex-associated flaviviruses, have historically been defined using virus detection in field-collected mosquitoes, mosquito feeding patterns, and vector competence, which quantifies the intrinsic ability of a mosquito to become infected with and transmit a virus during a subsequent blood feed. Herein, we quantitatively synthesize data from 68 laboratory-based vector competence studies of 111 mosquito-virus pairings of Australian mosquito species and viruses of public health concern to further substantiate existing canonical vector-virus groupings and quantify variation within these groupings. Our synthesis reinforces current canonical vector-virus groupings but reveals substantial variation within them. While Aedes species were generally the most competent vectors of canonical "Aedes-associated flaviviruses" (such as dengue, Zika, and yellow fever viruses), there are some notable exceptions; for example, Aedes notoscriptus is an incompetent vector of dengue viruses. Culex spp. were the most competent vectors of many traditionally Culex-associated flaviviruses including West Nile, Japanese encephalitis and Murray Valley encephalitis viruses, although some Aedes spp. are also moderately competent vectors of these viruses. Conversely, many different mosquito genera were associated with the transmission of the arthritogenic alphaviruses, Ross River, Barmah Forest, and chikungunya viruses. We also confirm that vector competence is impacted by multiple barriers to infection and transmission within the mesenteron and salivary glands of the mosquito. Although these barriers represent important bottlenecks, species that were susceptible to infection with a virus were often likely to transmit it. Importantly, this synthesis provides essential information on what species need to be targeted in mosquito control programs.

Chopping the tail: How preventing superspreading can help to maintain COVID-19 control.

Disease transmission is notoriously heterogeneous, and SARS-CoV-2 is no exception. A skewed distribution where few individuals or events are responsible for the majority of transmission can result in explosive, superspreading events, which produce rapid and volatile epidemic dynamics, especially early or late in epidemics. Anticipating and preventing superspreading events can produce large reductions in overall transmission rates. Here, we present a stochastic compartmental (SEIR) epidemiological model framework for estimating transmission parameters from multiple imperfectly observed data streams, including reported cases, deaths, and mobile phone-based mobility that incorporates individual-level heterogeneity in transmission using previous estimates for SARS-CoV-1 and SARS-CoV-2. We parameterize the model for COVID-19 epidemic dynamics by estimating a time-varying transmission rate that incorporates the impact of non-pharmaceutical intervention strategies that change over time, in five epidemiologically distinct settings-Los Angeles and Santa Clara Counties, California; Seattle (King County), Washington; Atlanta (Dekalb and Fulton Counties), Georgia; and Miami (Miami-Dade County), Florida. We find that the effective reproduction number (RE) dropped below 1 rapidly in all five locations following social distancing orders in mid-March, 2020, but that gradually increasing mobility starting around mid-April led to an RE once again above 1 in late May (Los Angeles, Miami, and Atlanta) or early June (Santa Clara County and Seattle). However, we find that increased social distancing starting in mid-July in response to epidemic resurgence once again dropped RE below 1 in all locations by August 14. We next used the fitted model to ask: how does truncating the individual-level transmission rate distribution (which removes periods of time with especially high individual transmission rates and thus models superspreading events) affect epidemic dynamics and control? We find that interventions that truncate the transmission rate distribution while partially relaxing social distancing are broadly effective, with impacts on epidemic growth on par with the strongest population-wide social distancing observed in April, 2020. Given that social distancing interventions will be needed to maintain epidemic control until a vaccine becomes widely available, "chopping off the tail" to reduce the probability of superspreading events presents a promising option to alleviate the need for extreme general social distancing.

Physiology and ecology combine to determine host and vector importance for Ross River virus.

Identifying the key vector and host species that drive the transmission of zoonotic pathogens is notoriously difficult but critical for disease control. We present a nested approach for quantifying the importance of host and vectors that integrates species' physiological competence with their ecological traits. We apply this framework to a medically important arbovirus, Ross River virus (RRV), in Brisbane, Australia. We find that vertebrate hosts with high physiological competence are not the most important for community transmission; interactions between hosts and vectors largely underpin the importance of host species. For vectors, physiological competence is highly important. Our results identify primary and secondary vectors of RRV and suggest two potential transmission cycles in Brisbane: an enzootic cycle involving birds and an urban cycle involving humans. The framework accounts for uncertainty from each fitted statistical model in estimates of species' contributions to transmission and has has direct application to other zoonotic pathogens.

Human-mediated impacts on biodiversity and the consequences for zoonotic disease spillover.

Human-mediated changes to natural ecosystems have consequences for both ecosystem and human health. Historically, efforts to preserve or restore 'biodiversity' can seem to be in opposition to human interests. However, the integration of biodiversity conservation and public health has gained significant traction in recent years, and new efforts to identify solutions that benefit both environmental and human health are ongoing. At the forefront of these efforts is an attempt to clarify ways in which biodiversity conservation can help reduce the risk of zoonotic spillover of pathogens from wild animals, sparking epidemics and pandemics in humans and livestock. However, our understanding of the mechanisms by which biodiversity change influences the spillover process is incomplete, limiting the application of integrated strategies aimed at achieving positive outcomes for both conservation and disease management. Here, we review the literature, considering a broad scope of biodiversity dimensions, to identify cases where zoonotic pathogen spillover is mechanistically linked to changes in biodiversity. By reframing the discussion around biodiversity and disease using mechanistic evidence - while encompassing multiple aspects of biodiversity including functional diversity, landscape diversity, phenological diversity, and interaction diversity - we work toward general principles that can guide future research and more effectively integrate the related goals of biodiversity conservation and spillover prevention. We conclude by summarizing how these principles could be used to integrate the goal of spillover prevention into ongoing biodiversity conservation initiatives.

Chopping the tail: how preventing superspreading can help to maintain COVID-19 control.

Disease transmission is notoriously heterogeneous, and SARS-CoV-2 is no exception. A skewed distribution where few individuals or events are responsible for the majority of transmission can result in explosive, superspreading events, which produce rapid and volatile epidemic dynamics, especially early or late in epidemics. Anticipating and preventing superspreading events can produce large reductions in overall transmission rates. Here, we present a compartmental (SEIR) epidemiological model framework for estimating transmission parameters from multiple imperfectly observed data streams, including reported cases, deaths, and mobile phone-based mobility that incorporates individual-level heterogeneity in transmission using previous estimates for SARS-CoV-1 and SARS-CoV-2. We parameterize the model for COVID-19 epidemic dynamics by estimating a time-varying transmission rate that incorporates the impact of non-pharmaceutical intervention strategies that change over time, in five epidemiologically distinct settings---Los Angeles and Santa Clara Counties, California; Seattle (King County), Washington; Atlanta (Dekalb and Fulton Counties), Georgia; and Miami (Miami-Dade County), Florida. We find the effective reproduction number R E dropped below 1 rapidly following social distancing orders in mid-March, 2020 and remained there into June in Santa Clara County and Seattle, but climbed above 1 in late May in Los Angeles, Miami, and Atlanta, and has trended upward in all locations since April. With the fitted model, we ask: how does truncating the tail of the individual-level transmission rate distribution affect epidemic dynamics and control? We find interventions that truncate the transmission rate distribution while partially relaxing social distancing are broadly effective, with impacts on epidemic growth on par with the strongest population-wide social distancing observed in April, 2020. Given that social distancing interventions will be needed to maintain epidemic control until a vaccine becomes widely available, "chopping off the tail" to reduce the probability of superspreading events presents a promising option to alleviate the need for extreme general social distancing.

The impact of long-term non-pharmaceutical interventions on COVID-19 epidemic dynamics and control.

Non-pharmaceutical interventions to combat COVID-19 transmission have worked to slow the spread of the epidemic but can have high socio-economic costs. It is critical we understand the efficacy of non-pharmaceutical interventions to choose a safe exit strategy. Many current models are not suitable for assessing exit strategies because they do not account for epidemic resurgence when social distancing ends prematurely (e.g., statistical curve fits) nor permit scenario exploration in specific locations. We developed an SEIR-type mechanistic epidemiological model of COVID-19 dynamics to explore temporally variable non-pharmaceutical interventions. We provide an interactive tool and code to estimate the transmission parameter, ß, and the effective reproduction number, R eff . We fit the model to Santa Clara County, California, where an early epidemic start date and early shelter-in-place orders could provide a model for other regions. As of April 22, 2020, we estimate an R eff of 0.982 (95% CI: 0.849 - 1.107) in Santa Clara County. After June 1 (the end-date for Santa Clara County shelter-in-place as of April 27), we estimate a shift to partial social distancing, combined with rigorous testing and isolation of symptomatic individuals, is a viable alternative to indefinitely maintaining shelter-in-place. We also estimate that if Santa Clara County had waited one week longer before issuing shelter-in-place orders, 95 additional people would have died by April 22 (95% CI: 7 - 283). Given early life-saving shelter-in-place orders in Santa Clara County, longer-term moderate social distancing and testing and isolation of symptomatic individuals have the potential to contain the size and toll of the COVID-19 pandemic in Santa Clara County, and may be effective in other locations.

Predicting West Nile virus transmission in North American bird communities using phylogenetic mixed effects models and eBird citizen science data.

BACKGROUND: West Nile virus (WNV) is a mosquito-transmitted disease of birds that has caused bird population declines and can spill over into human populations. Previous research has identified bird species that infect a large fraction of the total pool of infected mosquitoes and correlate with human infection risk; however, these analyses cover small spatial regions and cannot be used to predict transmission in bird communities in which these species are rare or absent. Here we present a mechanistic model for WNV transmission that predicts WNV spread (R0) in any bird community in North America by scaling up from the physiological responses of individual birds to transmission at the level of the community. We predict unmeasured bird species' responses to infection using phylogenetic imputation, based on these species' phylogenetic relationships with bird species with measured responses. RESULTS: We focused our analysis on Texas, USA, because it is among the states with the highest total incidence of WNV in humans and is well sampled by birders in the eBird database. Spatio-temporal patterns: WNV transmission is primarily driven by temperature variation across time and space, and secondarily by bird community composition. In Texas, we predicted WNV R0 to be highest in the spring and fall when temperatures maximize the product of mosquito transmission and survival probabilities. In the most favorable months for WNV transmission (April, May, September and October), we predicted R0 to be highest in the "Piney Woods" and "Oak Woods & Prairies" ecoregions of Texas, and lowest in the "High Plains" and "South Texas Brush County" ecoregions. Dilution effect: More abundant bird species are more competent hosts for WNV, and predicted WNV R0 decreases with increasing species richness. Keystone species: We predicted that northern cardinals (Cardinalis cardinalis) are the most important hosts for amplifying WNV and that mourning doves (Zenaida macroura) are the most important sinks of infection across Texas. CONCLUSIONS: Despite some data limitations, we demonstrate the power of phylogenetic imputation in predicting disease transmission in heterogeneous host communities. Our mechanistic modeling framework shows promise both for assisting future analyses on transmission and spillover in heterogeneous multispecies pathogen systems and for improving model transparency by clarifying assumptions, choices and shortcomings in complex ecological analyses.

Anti-predator behavioral variation among Physa acuta in response to temporally fluctuating predation risk by Procambarus.

Research in behavioral ecology routinely quantifies individual variation in behavior using transitions between discrete environments, for example prey moving from a no predator to predator treatment. This research often ignores behavioral variation in response to temporal fluctuations in environmental conditions around an unchanging mean environment. In this study we evaluate the effects of temporal fluctuations in predation risk (predator cue concentration of Procambarus spp.), without the confounding effects of a changing mean, on among-individual variation in anti-predator behavior in freshwater snails (Physa acuta). We also evaluate how the interaction between environmental and individual variation affects snail survival and reproduction by exposing snails to lethal predators following the behavioral assays. Our analyses revealed a trend towards higher among-individual variation in mean behavior when snails were exposed to intermediate levels of environmental variation compared to highly variable or constant environments. However, because of large uncertainty in estimates of among-individual variation, differences among treatments were indistinguishable from noise for most, but not all behaviors. In the lethal predator trials, snail survival and time to mortality was the lowest in the high variation environment. Also, as environmental variation increased snail egg production decreased and snails laid more of their eggs underneath a provided shelter.

A practical guide and power analysis for GLMMs: detecting among treatment variation in random effects.

In ecology and evolution generalized linear mixed models (GLMMs) are becoming increasingly used to test for differences in variation by treatment at multiple hierarchical levels. Yet, the specific sampling schemes that optimize the power of an experiment to detect differences in random effects by treatment/group remain unknown. In this paper we develop a blueprint for conducting power analyses for GLMMs focusing on detecting differences in variance by treatment. We present parameterization and power analyses for random-intercepts and random-slopes GLMMs because of their generality as focal parameters for most applications and because of their immediate applicability to emerging questions in the field of behavioral ecology. We focus on the extreme case of hierarchically structured binomial data, though the framework presented here generalizes easily to any error distribution model. First, we determine the optimal ratio of individuals to repeated measures within individuals that maximizes power to detect differences by treatment in among-individual variation in intercept, among-individual variation in slope, and within-individual variation in intercept. Second, we explore how power to detect differences in target variance parameters is affected by total variation. Our results indicate heterogeneity in power across ratios of individuals to repeated measures with an optimal ratio determined by both the target variance parameter and total sample size. Additionally, power to detect each variance parameter was low overall (in most cases >1,000 total observations per treatment needed to achieve 80% power) and decreased with increasing variance in non-target random effects. With growing interest in variance as the parameter of inquiry, these power analyses provide a crucial component for designing experiments focused on detecting differences in variance. We hope to inspire novel experimental designs in ecology and evolution investigating the causes and implications of individual-level phenotypic variance, such as the adaptive significance of within-individual variation.