Virome Data Explorer: A web resource to longitudinally explore respiratory viral infections, their interactions with other pathogens and host transcriptomic changes in over 100 people.

Viral respiratory infections are an important public health concern due to their prevalence, transmissibility, and potential to cause serious disease. Disease severity is the product of several factors beyond the presence of the infectious agent, including specific host immune responses, host genetic makeup, and bacterial coinfections. To understand these interactions within natural infections, we designed a longitudinal cohort study actively surveilling respiratory viruses over the course of 19 months (2016 to 2018) in a diverse cohort in New York City. We integrated the molecular characterization of 800+ nasopharyngeal samples with clinical data from 104 participants. Transcriptomic data enabled the identification of respiratory pathogens in nasopharyngeal samples, the characterization of markers of immune response, the identification of signatures associated with symptom severity, individual viruses, and bacterial coinfections. Specific results include a rapid restoration of baseline conditions after infection, significant transcriptomic differences between symptomatic and asymptomatic infections, and qualitatively similar responses across different viruses. We created an interactive computational resource (Virome Data Explorer) to facilitate access to the data and visualization of analytical results.

Burden and characteristics of COVID-19 in the United States during 2020.

The COVID-19 pandemic disrupted health systems and economies throughout the world during 2020 and was particularly devastating for the United States, which experienced the highest numbers of reported cases and deaths during 20201-3. Many of the epidemiological features responsible for observed rates of morbidity and mortality have been reported4-8; however, the overall burden and characteristics of COVID-19 in the United States have not been comprehensively quantified. Here we use a data-driven model-inference approach to simulate the pandemic at county-scale in the United States during 2020 and estimate critical, time-varying epidemiological properties underpinning the dynamics of the virus. The pandemic in the United States during 2020 was characterized by national ascertainment rates that increased from 11.3% (95% credible interval (CI): 8.3-15.9%) in March to 24.5% (18.6-32.3%) during December. Population susceptibility at the end of the year was 69.0% (63.6-75.4%), indicating that about one third of the US population had been infected. Community infectious rates, the percentage of people harbouring a contagious infection, increased above 0.8% (0.6-1.0%) before the end of the year, and were as high as 2.4% in some major metropolitan areas. By contrast, the infection fatality rate fell to 0.3% by year's end.

Multimodeling approach to evaluating the efficacy of layering pharmaceutical and nonpharmaceutical interventions for influenza pandemics.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Geographic Variation, Economic Activity, and Labor Market Characteristics in Trajectories of Suicide in the United States, 2008-2020.

Suicide rates in the United States have increased over the past 15 years, with substantial geographic variation in these increases; yet there have been few attempts to cluster counties by the magnitude of suicide rate changes according to intercept and slope or to identify the economic precursors of increases. We used vital statistics data and growth mixture models to identify clusters of counties by their magnitude of suicide growth from 2008 to 2020 and examined associations with county economic and labor indices. Our models identified 5 clusters, each differentiated by intercept and slope magnitude, with the highest-rate cluster (4% of counties) being observed mainly in sparsely populated areas in the West and Alaska, starting the time series at 25.4 suicides per 100,000 population, and exhibiting the steepest increase in slope (0.69/100,000/year). There was no cluster for which the suicide rate was stable or declining. Counties in the highest-rate cluster were more likely to have agricultural and service economies and less likely to have urban professional economies. Given the increased burden of suicide, with no clusters of counties improving over time, additional policy and prevention efforts are needed, particularly targeted at rural areas in the West.

Clinical and economic outcomes of a pharmacogenomics-enriched comprehensive medication management program in a self-insured employee population.

Clinical and economic outcomes from a pharmacogenomics-enriched comprehensive medication management program were evaluated over 26 months in a self-insured U.S. employee population (n = 452 participants; n = 1500 controls) using propensity matched pre-post design with adjusted negative binomial and linear regression models. After adjusting for baseline covariates, program participation was associated with 39% fewer inpatient (p = 0.05) and 39% fewer emergency department (p = 0.002) visits, and with 21% more outpatient visits (p < 0.001) in the follow-up period compared to the control group. Results show pharmacogenomics-enriched comprehensive medication management can favorably impact healthcare utilization in a self-insured employer population by reducing emergency department and inpatient visits and can offer the potential for cost savings. Self-insured employers may consider implementing pharmacogenomics-enriched comprehensive medication management to improve the healthcare of their employees.

Development of Accurate Long-lead COVID-19 Forecast.

Coronavirus disease 2019 (COVID-19) will likely remain a major public health burden; accurate forecast of COVID-19 epidemic outcomes several months into the future is needed to support more proactive planning. Here, we propose strategies to address three major forecast challenges, i.e., error growth, the emergence of new variants, and infection seasonality. Using these strategies in combination we generate retrospective predictions of COVID-19 cases and deaths 6 months in the future for 10 representative US states. Tallied over >25,000 retrospective predictions through September 2022, the forecast approach using all three strategies consistently outperformed a baseline forecast approach without these strategies across different variant waves and locations, for all forecast targets. Overall, probabilistic forecast accuracy improved by 64% and 38% and point prediction accuracy by 133% and 87% for cases and deaths, respectively. Real-time 6-month lead predictions made in early October 2022 suggested large attack rates in most states but a lower burden of deaths than previous waves during October 2022 -March 2023; these predictions are in general accurate compared to reported data. The superior skill of the forecast methods developed here demonstrate means for generating more accurate long-lead forecast of COVID-19 and possibly other infectious diseases.

Inference of transmission dynamics and retrospective forecast of invasive meningococcal disease.

The pathogenic bacteria Neisseria meningitidis, which causes invasive meningococcal disease (IMD), predominantly colonizes humans asymptomatically; however, invasive disease occurs in a small proportion of the population. Here, we explore the seasonality of IMD and develop and validate a suite of models for simulating and forecasting disease outcomes in the United States. We combine the models into multi-model ensembles (MME) based on the past performance of the individual models, as well as a naive equally weighted aggregation, and compare the retrospective forecast performance over a six-month forecast horizon. Deployment of the complete vaccination regimen, introduced in 2011, coincided with a change in the periodicity of IMD, suggesting altered transmission dynamics. We found that a model forced with the period obtained by local power wavelet decomposition best fit and forecast observations. In addition, the MME performed the best across the entire study period. Finally, our study included US-level data until 2022, allowing study of a possible IMD rebound after relaxation of non-pharmaceutical interventions imposed in response to the COVID-19 pandemic; however, no evidence of a rebound was found. Our findings demonstrate the ability of process-based models to retrospectively forecast IMD and provide a first analysis of the seasonality of IMD before and after the complete vaccination regimen.

Hindcasts and forecasts of suicide mortality in US: A modeling study.

Deaths by suicide, as well as suicidal ideations, plans and attempts, have been increasing in the US for the past two decades. Deployment of effective interventions would require timely, geographically well-resolved estimates of suicide activity. In this study, we evaluated the feasibility of a two-step process for predicting suicide mortality: a) generation of hindcasts, mortality estimates for past months for which observational data would not have been available if forecasts were generated in real-time; and b) generation of forecasts with observational data augmented with hindcasts. Calls to crisis hotline services and online queries to the Google search engine for suicide-related terms were used as proxy data sources to generate hindcasts. The primary hindcast model (auto) is an Autoregressive Integrated Moving average model (ARIMA), trained on suicide mortality rates alone. Three regression models augment hindcast estimates from auto with call rates (calls), GHT search rates (ght) and both datasets together (calls_ght). The 4 forecast models used are ARIMA models trained with corresponding hindcast estimates. All models were evaluated against a baseline random walk with drift model. Rolling monthly 6-month ahead forecasts for all 50 states between 2012 and 2020 were generated. Quantile score (QS) was used to assess the quality of the forecast distributions. Median QS for auto was better than baseline (0.114 vs. 0.21. Median QS of augmented models were lower than auto, but not significantly different from each other (Wilcoxon signed-rank test, p > .05). Forecasts from augmented models were also better calibrated. Together, these results provide evidence that proxy data can address delays in release of suicide mortality data and improve forecast quality. An operational forecast system of state-level suicide risk may be feasible with sustained engagement between modelers and public health departments to appraise data sources and methods as well as to continuously evaluate forecast accuracy.

A two-variant model of SARS-COV-2 transmission: estimating the characteristics of a newly emerging strain.

BACKGROUND: The Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses. METHODS: This paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference. RESULTS: The model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15-0.29) and transmission rate of 5.0 (95% CI 2.4-6.6) for the Omicron variant. CONCLUSIONS: The study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses.

Evaluating completion rates of COVID-19 contact tracing surveys in New York City.

IMPORTANCE: Contact tracing is the process of identifying people who have recently been in contact with someone diagnosed with an infectious disease. During an outbreak, data collected from contact tracing can inform interventions to reduce the spread of infectious diseases. Understanding factors associated with completion rates of contact tracing surveys can help design improved interview protocols for ongoing and future programs. OBJECTIVE: To identify factors associated with completion rates of COVID-19 contact tracing surveys in New York City (NYC) and evaluate the utility of a predictive model to improve completion rates, we analyze laboratory-confirmed and probable COVID-19 cases and their self-reported contacts in NYC from October 1st 2020 to May 10th 2021. METHODS: We analyzed 742,807 case investigation calls made during the study period. Using a log-binomial regression model, we examined the impact of age, time of day of phone call, and zip code-level demographic and socioeconomic factors on interview completion rates. We further developed a random forest model to predict the best phone call time and performed a counterfactual analysis to evaluate the change of completion rates if the predicative model were used. RESULTS: The percentage of contact tracing surveys that were completed was 79.4%, with substantial variations across ZIP code areas. Using a log-binomial regression model, we found that the age of index case (an individual who has tested positive through PCR or antigen testing and is thus subjected to a case investigation) had a significant effect on the completion of case investigation - compared with young adults (the reference group,24 years old < age < = 65 years old), the completion rate for seniors (age > 65 years old) were lower by 12.1% (95%CI: 11.1% - 13.3%), and the completion rate for youth group (age < = 24 years old) were lower by 1.6% (95%CI: 0.6% -2.6%). In addition, phone calls made from 6 to 9 pm had a 4.1% (95% CI: 1.8% - 6.3%) higher completion rate compared with the reference group of phone calls attempted from 12 and 3 pm. We further used a random forest algorithm to assess its potential utility for selecting the time of day of phone call. In counterfactual simulations, the overall completion rate in NYC was marginally improved by 1.2%; however, certain ZIP code areas had improvements up to 7.8%. CONCLUSION: These findings suggest that age and time of day of phone call were associated with completion rates of case investigations. It is possible to develop predictive models to estimate better phone call time for improving completion rates in certain communities.

Identifying asymptomatic spreaders of antimicrobial-resistant pathogens in hospital settings.

Antimicrobial-resistant organisms (AMROs) can colonize people without symptoms for long periods of time, during which these agents can spread unnoticed to other patients in healthcare systems. The accurate identification of asymptomatic spreaders of AMRO in hospital settings is essential for supporting the design of interventions against healthcare-associated infections (HAIs). However, this task remains challenging because of limited observations of colonization and the complicated transmission dynamics occurring within hospitals and the broader community. Here, we study the transmission of methicillin-resistant Staphylococcus aureus (MRSA), a prevalent AMRO, in 66 Swedish hospitals and healthcare facilities with inpatients using a data-driven, agent-based model informed by deidentified real-world hospitalization records. Combining the transmission model, patient-to-patient contact networks, and sparse observations of colonization, we develop and validate an individual-level inference approach that estimates the colonization probability of individual hospitalized patients. For both model-simulated and historical outbreaks, the proposed method supports the more accurate identification of asymptomatic MRSA carriers than other traditional approaches. In addition, in silica control experiments indicate that interventions targeted to inpatients with a high-colonization probability outperform heuristic strategies informed by hospitalization history and contact tracing.

Association Between Prosuicide Website Searches Through Google and Suicide Death in the United States From 2010 to 2021: Lagged Time-Series Analysis.

BACKGROUND:  The rate of suicide death has been increasing, making understanding risk factors of growing importance. While exposure to explicit suicide-related media, such as description of means in news reports or sensationalized fictional portrayal, is known to increase population suicide rates, it is not known whether prosuicide website forums, which often promote or facilitate information about fatal suicide means, are related to change in suicide deaths overall or by specific means. OBJECTIVE:  This study aimed to estimate the association of the frequency of Google searches of known prosuicide web forums and content with death by suicide over time in the United States, by age, sex, and means of death. METHODS:  National monthly Google search data for names of common prosuicide websites between January 2010 and December 2021 were extracted from Google Health Trends API (application programming interface). Suicide deaths were identified using the CDC (Centers for Disease Control and Prevention) National Vital Statistics System (NVSS), and 3 primary means of death were identified (poisoning, suffocation, and firearm). Distributed lag nonlinear models (DLNMs) were then used to estimate the lagged association between the number of Google searches on suicide mortality, stratified by age, sex, and means, and adjusted for month. Sensitivity analyses, including using autoregressive integrated moving average (ARIMA) modeling approaches, were also conducted. RESULTS:  Months in the United States in which search rates for prosuicide websites increased had more documented deaths by intentional poisoning and suffocation among both adolescents and adults. For example, the risk of poisoning suicide among youth and young adults (age 10-24 years) was 1.79 (95% CI 1.06-3.03) times higher in months with 22 searches per 10 million as compared to 0 searches. The risk of poisoning suicide among adults aged 25-64 was 1.10 (95% CI 1.03-1.16) times higher 1 month after searches reached 9 per 10 million compared with 0 searches. We also observed that increased search rates were associated with fewer youth suicide deaths by firearms with a 3-month time lag for adolescents. These models were robust to sensitivity tests. CONCLUSIONS:  Although more analysis is needed, the findings are suggestive of an association between increased prosuicide website access and increased suicide deaths, specifically deaths by poisoning and suffocation. These findings emphasize the need to further investigate sites containing potentially dangerous information and their associations with deaths by suicide, as they may affect vulnerable individuals.

Internet Search Activity for Intentional Self-Harm Forums After a High-Profile News Publication: Interrupted Time Series Analysis.

Searches for "pro-suicide" websites in the United States peaked during the week a high-profile news story was published and remained elevated for 6 months afterward, highlighting the need to avoid mentioning specific sources of explicit suicide instructions in media publications.

Waterborne Infectious Diseases Associated with Exposure to Tropical Cyclonic Storms, United States, 1996-2018.

In the United States, tropical cyclones cause destructive flooding that can lead to adverse health outcomes. Storm-driven flooding contaminates environmental, recreational, and drinking water sources, but few studies have examined effects on specific infections over time. We used 23 years of exposure and case data to assess the effects of tropical cyclones on 6 waterborne diseases in a conditional quasi-Poisson model. We separately defined storm exposure for windspeed, rainfall, and proximity to the storm track. Exposure to storm-related rainfall was associated with a 48% (95% CI 27%-69%) increase in Shiga toxin-producing Escherichia coli infections 1 week after storms and a 42% (95% CI 22%-62%) in increase Legionnaires' disease 2 weeks after storms. Cryptosporidiosis cases increased 52% (95% CI 42%-62%) during storm weeks but declined over ensuing weeks. Cyclones are a risk to public health that will likely become more serious with climate change and aging water infrastructure systems.

Longitudinal Association of COVID-19 Hospitalization and Death with Online Search for Loss of Smell or Taste.

Surveillance of COVID-19 is challenging but critical for mitigating disease, particularly if predictive of future disease burden. We report a robust multiyear lead-lag association between internet search activity for loss of smell or taste and COVID-19-associated hospitalization and deaths. These search data could help predict COVID-19 surges.

Challenges in Forecasting Antimicrobial Resistance.

Antimicrobial resistance is a major threat to human health. Since the 2000s, computational tools for predicting infectious diseases have been greatly advanced; however, efforts to develop real-time forecasting models for antimicrobial-resistant organisms (AMROs) have been absent. In this perspective, we discuss the utility of AMRO forecasting at different scales, highlight the challenges in this field, and suggest future research priorities. We also discuss challenges in scientific understanding, access to high-quality data, model calibration, and implementation and evaluation of forecasting models. We further highlight the need to initiate research on AMRO forecasting using currently available data and resources to galvanize the research community and address initial practical questions.

Inference and dynamic simulation of malaria using a simple climate-driven entomological model of malaria transmission.

Given the crucial role of climate in malaria transmission, many mechanistic models of malaria represent vector biology and the parasite lifecycle as functions of climate variables in order to accurately capture malaria transmission dynamics. Lower dimension mechanistic models that utilize implicit vector dynamics have relied on indirect climate modulation of transmission processes, which compromises investigation of the ecological role played by climate in malaria transmission. In this study, we develop an implicit process-based malaria model with direct climate-mediated modulation of transmission pressure borne through the Entomological Inoculation Rate (EIR). The EIR, a measure of the number of infectious bites per person per unit time, includes the effects of vector dynamics, resulting from mosquito development, survivorship, feeding activity and parasite development, all of which are moderated by climate. We combine this EIR-model framework, which is driven by rainfall and temperature, with Bayesian inference methods, and evaluate the model's ability to simulate local transmission across 42 regions in Rwanda over four years. Our findings indicate that the biologically-motivated, EIR-model framework is capable of accurately simulating seasonal malaria dynamics and capturing of some of the inter-annual variation in malaria incidence. However, the model unsurprisingly failed to reproduce large declines in malaria transmission during 2018 and 2019 due to elevated anti-malaria measures, which were not accounted for in the model structure. The climate-driven transmission model also captured regional variation in malaria incidence across Rwanda's diverse climate, while identifying key entomological and epidemiological parameters important to seasonal malaria dynamics. In general, this new model construct advances the capabilities of implicitly-forced lower dimension dynamical malaria models by leveraging climate drivers of malaria ecology and transmission.

Epidemic management and control through risk-dependent individual contact interventions.

Testing, contact tracing, and isolation (TTI) is an epidemic management and control approach that is difficult to implement at scale because it relies on manual tracing of contacts. Exposure notification apps have been developed to digitally scale up TTI by harnessing contact data obtained from mobile devices; however, exposure notification apps provide users only with limited binary information when they have been directly exposed to a known infection source. Here we demonstrate a scalable improvement to TTI and exposure notification apps that uses data assimilation (DA) on a contact network. Network DA exploits diverse sources of health data together with the proximity data from mobile devices that exposure notification apps rely upon. It provides users with continuously assessed individual risks of exposure and infection, which can form the basis for targeting individual contact interventions. Simulations of the early COVID-19 epidemic in New York City are used to establish proof-of-concept. In the simulations, network DA identifies up to a factor 2 more infections than contact tracing when both harness the same contact data and diagnostic test data. This remains true even when only a relatively small fraction of the population uses network DA. When a sufficiently large fraction of the population (≳ 75%) uses network DA and complies with individual contact interventions, targeting contact interventions with network DA reduces deaths by up to a factor 4 relative to TTI. Network DA can be implemented by expanding the computational backend of existing exposure notification apps, thus greatly enhancing their capabilities. Implemented at scale, it has the potential to precisely and effectively control future epidemics while minimizing economic disruption.

Community transmission of SARS-CoV-2 during the Delta wave in New York City.

BACKGROUND: Understanding community transmission of SARS-CoV-2 variants of concern (VOCs) is critical for disease control in the post pandemic era. The Delta variant (B.1.617.2) emerged in late 2020 and became the dominant VOC globally in the summer of 2021. While the epidemiological features of the Delta variant have been extensively studied, how those characteristics shaped community transmission in urban settings remains poorly understood. METHODS: Using high-resolution contact tracing data and testing records, we analyze the transmission of SARS-CoV-2 during the Delta wave within New York City (NYC) from May 2021 to October 2021. We reconstruct transmission networks at the individual level and across 177 ZIP code areas, examine network structure and spatial spread patterns, and use statistical analysis to estimate the effects of factors associated with COVID-19 spread. RESULTS: We find considerable individual variations in reported contacts and secondary infections, consistent with the pre-Delta period. Compared with earlier waves, Delta-period has more frequent long-range transmission events across ZIP codes. Using socioeconomic, mobility and COVID-19 surveillance data at the ZIP code level, we find that a larger number of cumulative cases in a ZIP code area is associated with reduced within- and cross-ZIP code transmission and the number of visitors to each ZIP code is positively associated with the number of non-household infections identified through contact tracing and testing. CONCLUSIONS: The Delta variant produced greater long-range spatial transmission across NYC ZIP code areas, likely caused by its increased transmissibility and elevated human mobility during the study period. Our findings highlight the potential role of population immunity in reducing transmission of VOCs. Quantifying variability of immunity is critical for identifying subpopulations susceptible to future VOCs. In addition, non-pharmaceutical interventions limiting human mobility likely reduced SARS-CoV-2 spread over successive pandemic waves and should be encouraged for reducing transmission of future VOCs.