Characterizing collective physical distancing in the U.S. during the first nine months of the COVID-19 pandemic.

The COVID-19 pandemic offers an unprecedented natural experiment providing insights into the emergence of collective behavioral changes of both exogenous (government mandated) and endogenous (spontaneous reaction to infection risks) origin. Here, we characterize collective physical distancing-mobility reductions, minimization of contacts, shortening of contact duration-in response to the COVID-19 pandemic in the pre-vaccine era by analyzing de-identified, privacy-preserving location data for a panel of over 5.5 million anonymized, opted-in U.S. devices. We define five indicators of users' mobility and proximity to investigate how the emerging collective behavior deviates from typical pre-pandemic patterns during the first nine months of the COVID-19 pandemic. We analyze both the dramatic changes due to the government mandated mitigation policies and the more spontaneous societal adaptation into a new (physically distanced) normal in the fall 2020. Using the indicators here defined we show that: a) during the COVID-19 pandemic, collective physical distancing displayed different phases and was heterogeneous across geographies, b) metropolitan areas displayed stronger reductions in mobility and contacts than rural areas; c) stronger reductions in commuting patterns are observed in geographical areas with a higher share of teleworkable jobs; d) commuting volumes during and after the lockdown period negatively correlate with unemployment rates; and e) increases in contact indicators correlate with future values of new deaths at a lag consistent with epidemiological parameters and surveillance reporting delays. In conclusion, this study demonstrates that the framework and indicators here presented can be used to analyze large-scale social distancing phenomena, paving the way for their use in future pandemics to analyze and monitor the effects of pandemic mitigation plans at the national and international levels.

Wastewater surveillance facilitates climate change-resilient pathogen monitoring.

Traditional disease surveillance systems are ill-equipped to handle climate change-driven shifts in pathogen dynamics. If paired with wastewater surveillance, a cost-effective and scalable approach for generating high-resolution health data, such next-generation systems can enable effective resource allocation and delivery of targeted interventions.

Wastewater monitoring can anchor global disease surveillance systems.

To inform the development of global wastewater monitoring systems, we surveyed programmes in 43 countries. Most programmes monitored predominantly urban populations. In high-income countries (HICs), composite sampling at centralised treatment plants was most common, whereas grab sampling from surface waters, open drains, and pit latrines was more typical in low-income and middle-income countries (LMICs). Almost all programmes analysed samples in-country, with an average processing time of 2·3 days in HICs and 4·5 days in LMICs. Whereas 59% of HICs regularly monitored wastewater for SARS-CoV-2 variants, only 13% of LMICs did so. Most programmes share their wastewater data internally, with partnering organisations, but not publicly. Our findings show the richness of the existing wastewater monitoring ecosystem. With additional leadership, funding, and implementation frameworks, thousands of individual wastewater initiatives can coalesce into an integrated, sustainable network for disease surveillance-one that minimises the risk of overlooking future global health threats.

COVID-19 amplified racial disparities in the US criminal legal system.

The criminal legal system in the USA drives an incarceration rate that is the highest on the planet, with disparities by class and race among its signature features1-3. During the first year of the coronavirus disease 2019 (COVID-19) pandemic, the number of incarcerated people in the USA decreased by at least 17%-the largest, fastest reduction in prison population in American history4. Here we ask how this reduction influenced the racial composition of US prisons and consider possible mechanisms for these dynamics. Using an original dataset curated from public sources on prison demographics across all 50 states and the District of Columbia, we show that incarcerated white people benefited disproportionately from the decrease in the US prison population and that the fraction of incarcerated Black and Latino people sharply increased. This pattern of increased racial disparity exists across prison systems in nearly every state and reverses a decade-long trend before 2020 and the onset of COVID-19, when the proportion of incarcerated white people was increasing amid declining numbers of incarcerated Black people5. Although a variety of factors underlie these trends, we find that racial inequities in average sentence length are a major contributor. Ultimately, this study reveals how disruptions caused by COVID-19 exacerbated racial inequalities in the criminal legal system, and highlights key forces that sustain mass incarceration. To advance opportunities for data-driven social science, we publicly released the data associated with this study at Zenodo6.

Forecasting hospital-level COVID-19 admissions using real-time mobility data.

BACKGROUND: For each of the COVID-19 pandemic waves, hospitals have had to plan for deploying surge capacity and resources to manage large but transient increases in COVID-19 admissions. While a lot of effort has gone into predicting regional trends in COVID-19 cases and hospitalizations, there are far fewer successful tools for creating accurate hospital-level forecasts. METHODS: Large-scale, anonymized mobile phone data has been shown to correlate with regional case counts during the first two waves of the pandemic (spring 2020, and fall/winter 2021). Building off this success, we developed a multi-step, recursive forecasting model to predict individual hospital admissions; this model incorporates the following data: (i) hospital-level COVID-19 admissions, (ii) statewide test positivity data, and (iii) aggregate measures of large-scale human mobility, contact patterns, and commuting volume. RESULTS: Incorporating large-scale, aggregate mobility data as exogenous variables in prediction models allows us to make hospital-specific COVID-19 admission forecasts 21 days ahead. We show this through highly accurate predictions of hospital admissions for five hospitals in Massachusetts during the first year of the COVID-19 pandemic. CONCLUSIONS: The high predictive capability of the model was achieved by combining anonymized, aggregated mobile device data about users' contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data. Mobility-informed forecasting models can increase the lead-time of accurate predictions for individual hospitals, giving managers valuable time to strategize how best to allocate resources to manage forthcoming surges.

During the COVID-19 pandemic, hospitals have needed to make challenging decisions around staffing and preparedness based on estimates of the number of admissions multiple weeks ahead. Forecasting techniques using methods from machine learning have been successfully applied to predict hospital admissions statewide, but the ability to accurately predict individual hospital admissions has proved elusive. Here, we incorporate details of the movement of people obtained from mobile phone data into a model that makes accurate predictions of the number of people who will be hospitalized 21 days ahead. This model will be useful for administrators and healthcare workers to plan staffing and discharge of patients to ensure adequate capacity to deal with forthcoming hospital admissions.

The ensemble of gene regulatory networks at mutation-selection balance.

The evolution of diverse phenotypes both involves and is constrained by molecular interaction networks. When these networks influence patterns of expression, we refer to them as gene regulatory networks (GRNs). Here, we develop a model of GRN evolution analogous to work from quasi-species theory, which is itself essentially the mutation-selection balance model from classical population genetics extended to multiple loci. With this GRN model, we prove that-across a broad spectrum of selection pressures-the dynamics converge to a stationary distribution over GRNs. Next, we show from first principles how the frequency of GRNs at equilibrium is related to the topology of the genotype network, in particular, via a specific network centrality measure termed the eigenvector centrality. Finally, we determine the structural characteristics of GRNs that are favoured in response to a range of selective environments and mutational constraints. Our work connects GRN evolution to quasi-species theory-and thus to classical populations genetics-providing a mechanistic explanation for the observed distribution of GRNs evolving in response to various evolutionary forces, and shows how complex fitness landscapes can emerge from simple evolutionary rules.

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.

A Family of Fitness Landscapes Modeled through Gene Regulatory Networks.

Fitness landscapes are a powerful metaphor for understanding the evolution of biological systems. These landscapes describe how genotypes are connected to each other through mutation and related through fitness. Empirical studies of fitness landscapes have increasingly revealed conserved topographical features across diverse taxa, e.g., the accessibility of genotypes and "ruggedness". As a result, theoretical studies are needed to investigate how evolution proceeds on fitness landscapes with such conserved features. Here, we develop and study a model of evolution on fitness landscapes using the lens of Gene Regulatory Networks (GRNs), where the regulatory products are computed from multiple genes and collectively treated as phenotypes. With the assumption that regulation is a binary process, we prove the existence of empirically observed, topographical features such as accessibility and connectivity. We further show that these results hold across arbitrary fitness functions and that a trade-off between accessibility and ruggedness need not exist. Then, using graph theory and a coarse-graining approach, we deduce a mesoscopic structure underlying GRN fitness landscapes where the information necessary to predict a population's evolutionary trajectory is retained with minimal complexity. Using this coarse-graining, we develop a bottom-up algorithm to construct such mesoscopic backbones, which does not require computing the genotype network and is therefore far more efficient than brute-force approaches. Altogether, this work provides mathematical results of high-dimensional fitness landscapes and a path toward connecting theory to empirical studies.

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.

Higher education responses to COVID-19 in the United States: Evidence for the impacts of university policy.

With a dataset of testing and case counts from over 1,400 institutions of higher education (IHEs) in the United States, we analyze the number of infections and deaths from SARS-CoV-2 in the counties surrounding these IHEs during the Fall 2020 semester (August to December, 2020). We find that counties with IHEs that remained primarily online experienced fewer cases and deaths during the Fall 2020 semester; whereas before and after the semester, these two groups had almost identical COVID-19 incidence. Additionally, we see fewer cases and deaths in counties with IHEs that reported conducting any on-campus testing compared to those that reported none. To perform these two comparisons, we used a matching procedure designed to create well-balanced groups of counties that are aligned as much as possible along age, race, income, population, and urban/rural categories-demographic variables that have been shown to be correlated with COVID-19 outcomes. We conclude with a case study of IHEs in Massachusetts-a state with especially high detail in our dataset-which further highlights the importance of IHE-affiliated testing for the broader community. The results in this work suggest that campus testing can itself be thought of as a mitigation policy and that allocating additional resources to IHEs to support efforts to regularly test students and staff would be beneficial to mitigating the spread of COVID-19 in a pre-vaccine environment.

Spatiotemporal invasion dynamics of SARS-CoV-2 lineage B.1.1.7 emergence.

Understanding the causes and consequences of the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is crucial to pandemic control yet difficult to achieve because they arise in the context of variable human behavior and immunity. We investigated the spatial invasion dynamics of lineage B.1.1.7 by jointly analyzing UK human mobility, virus genomes, and community-based polymerase chain reaction data. We identified a multistage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7's increased intrinsic transmissibility. We further explored how B.1.1.7 spread was shaped by nonpharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates.

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.

Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model.

About 20-25% of dengue virus (DENV) infections become symptomatic ranging from self-limiting fever to shock. Immune gene expression changes during progression to severe dengue have been documented in hospitalized patients; however, baseline or kinetic information is difficult to standardize in natural infection. Here we profile the host immunotranscriptome response in humans before, during, and after infection with a partially attenuated rDEN2Δ30 challenge virus (ClinicalTrials.gov NCT02021968). Inflammatory genes including type I interferon and viral restriction pathways are induced during DENV2 viremia and return to baseline after viral clearance, while others including myeloid, migratory, humoral, and growth factor immune regulation factors pathways are found at non-baseline levels post-viremia. Furthermore, pre-infection baseline gene expression is useful to predict rDEN2Δ30-induced immune responses and the development of rash. Our results suggest a distinct immunological profile for mild rDEN2Δ30 infection and offer new potential biomarkers for characterizing primary DENV infection.

The effect of eviction moratoria on the transmission of SARS-CoV-2.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.

Seeding COVID-19 across Sub-Saharan Africa: An Analysis of Reported Importation Events across 49 Countries.

The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. Whereas case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events in the SSA region. To capture epidemiological details related to early transmission events into and within countries, a line list was developed from publicly available data on institutional websites, situation reports, press releases, and social media accounts. The availability of indicators-gender, age, travel history, date of arrival in country, reporting date of confirmation, and how detected-for each imported case was assessed. We evaluated the relationship between the time to first reported importation and the Global Health Security Index (GHSI) overall score; 13,201 confirmed cases of COVID-19 were reported by 48 countries in SSA during the 54 days following the first known introduction to the region. Of the 2,516 cases for which travel history information was publicly available, 1,129 (44.9%) were considered importation events. Imported cases tended to be male (65.0%), with a median age of 41.0 years (range: 6 weeks-88 years; IQR: 31-54 years). A country's time to report its first importation was not related to the GHSI overall score, after controlling for air traffic. Countries in SSA generally reported with less publicly available detail over time and tended to have greater information on imported than local cases.

Mask-wearing and control of SARS-CoV-2 transmission in the USA: a cross-sectional study.

BACKGROUND: Face masks have become commonplace across the USA because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. Although evidence suggests that masks help to curb the spread of the disease, there is little empirical research at the population level. We investigate the association between self-reported mask-wearing, physical distancing, and SARS-CoV-2 transmission in the USA, along with the effect of statewide mandates on mask uptake. METHODS: Serial cross-sectional surveys were administered via a web platform to randomly surveyed US individuals aged 13 years and older, to query self-reports of face mask-wearing. Survey responses were combined with instantaneous reproductive number (Rt) estimates from two publicly available sources, the outcome of interest. Measures of physical distancing, community demographics, and other potential sources of confounding (from publicly available sources) were also assessed. We fitted multivariate logistic regression models to estimate the association between mask-wearing and community transmission control (Rt<1). Additionally, mask-wearing in 12 states was evaluated 2 weeks before and after statewide mandates. FINDINGS: 378 207 individuals responded to the survey between June 3 and July 27, 2020, of which 4186 were excluded for missing data. We observed an increasing trend in reported mask usage across the USA, although uptake varied by geography. A logistic model controlling for physical distancing, population demographics, and other variables found that a 10% increase in self-reported mask-wearing was associated with an increased odds of transmission control (odds ratio 3·53, 95% CI 2·03-6·43). We found that communities with high reported mask-wearing and physical distancing had the highest predicted probability of transmission control. Segmented regression analysis of reported mask-wearing showed no statistically significant change in the slope after mandates were introduced; however, the upward trend in reported mask-wearing was preserved. INTERPRETATION: The widespread reported use of face masks combined with physical distancing increases the odds of SARS-CoV-2 transmission control. Self-reported mask-wearing increased separately from government mask mandates, suggesting that supplemental public health interventions are needed to maximise adoption and help to curb the ongoing epidemic. FUNDING: Flu Lab, Google.org (via the Tides Foundation), National Institutes for Health, National Science Foundation, Morris-Singer Foundation, MOOD, Branco Weiss Fellowship, Ending Pandemics, Centers for Disease Control and Prevention (USA).

The effect of eviction moratoria on the transmission of SARS-CoV-2.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess municipal eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.