Reconciling the efficacy and effectiveness of masking on epidemic outcomes.

During the COVID-19 pandemic, mask wearing in public settings has been a key control measure. However, the reported effectiveness of masking has been much lower than laboratory measures of efficacy, leading to doubts on the utility of masking. Here, we develop an agent-based model that comprehensively accounts for individual masking behaviours and infectious disease dynamics, and test the impact of masking on epidemic outcomes. Using realistic inputs of mask efficacy and contact data at the individual level, the model reproduces the lower effectiveness as reported in randomized controlled trials. Model results demonstrate that transmission within households, where masks are rarely used, can substantially lower effectiveness, and reveal the interaction of nonlinear epidemic dynamics, control measures and potential measurement biases. Overall, model results show that, at the individual level, consistent masking can reduce the risk of first infection and, over time, reduce the frequency of repeated infection. At the population level, masking can provide direct protection to mask wearers, as well as indirect protection to non-wearers, collectively reducing epidemic intensity. These findings suggest it is prudent for individuals to use masks during an epidemic, and for policymakers to recognize the less-than-ideal effectiveness of masking when devising public health interventions.

Age-specific transmission dynamics of SARS-CoV-2 during the first 2 years of the pandemic.

During its first 2 years, the SARS-CoV-2 pandemic manifested as multiple waves shaped by complex interactions between variants of concern, non-pharmaceutical interventions, and the immunological landscape of the population. Understanding how the age-specific epidemiology of SARS-CoV-2 has evolved throughout the pandemic is crucial for informing policy decisions. In this article, we aimed to develop an inference-based modeling approach to reconstruct the burden of true infections and hospital admissions in children, adolescents, and adults over the seven waves of four variants (wild-type, Alpha, Delta, and Omicron BA.1) during the first 2 years of the pandemic, using the Netherlands as the motivating example. We find that reported cases are a considerable underestimate and a generally poor predictor of true infection burden, especially because case reporting differs by age. The contribution of children and adolescents to total infection and hospitalization burden increased with successive variants and was largest during the Omicron BA.1 period. However, the ratio of hospitalizations to infections decreased with each subsequent variant in all age categories. Before the Delta period, almost all infections were primary infections occurring in naive individuals. During the Delta and Omicron BA.1 periods, primary infections were common in children but relatively rare in adults who experienced either reinfections or breakthrough infections. Our approach can be used to understand age-specific epidemiology through successive waves in other countries where random community surveys uncovering true SARS-CoV-2 dynamics are absent but basic surveillance and statistics data are available.

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.

Excess Mortality in the United States, 2020-21: County-level Estimates for Population Groups and Associations with Social Vulnerability.

To assess the excess mortality burden of Covid-19 in the United States, we estimated sex, age and race stratified all-cause excess deaths in each county of the US during 2020 and 2021. Using spatial Bayesian models trained on all recorded deaths between 2003-2019, we estimated 463,187 (95% uncertainty interval (UI): 426,139 - 497,526) excess deaths during 2020, and 544,105 (95% UI: 492,202 - 592,959) excess deaths during 2021 nationally, with considerable geographical heterogeneity. Excess mortality rate (EMR) nearly doubled for each 10-year increase in age and was consistently higher among men than women. EMR in the Black population was 1.5 times that of the White population nationally and as high as 3.8 times in some states. Among the 25-54 year population excess mortality was highest in the American Indian/Alaskan Native (AI/AN) population among the four racial groups studied, and in a few states was as high as 6 times that of the White population. Strong association of EMR with county-level social vulnerability was estimated, including positive associations with prevalence of disability (standardized effect: 40.6 excess deaths per 100,000), older population (37.6), poverty (23.6), and unemployment (18.5), whereas population density (-50), higher education (-38.6), and income (-35.4) were protective. Together, these estimates provide a more reliable and comprehensive understanding of the mortality burden of the pandemic in the US thus far. They suggest that Covid-19 amplified social and racial disparities. Short-term measures to protect more vulnerable groups in future Covid-19 waves and systemic corrective steps to address long-term societal inequities are necessary.

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.

System identifiability in a time-evolving agent-based model.

Mathematical models are a valuable tool for studying and predicting the spread of infectious agents. The accuracy of model simulations and predictions invariably depends on the specification of model parameters. Estimation of these parameters is therefore extremely important; however, while some parameters can be derived from observational studies, the values of others are difficult to measure. Instead, models can be coupled with inference algorithms (i.e., data assimilation methods, or statistical filters), which fit model simulations to existing observations and estimate unobserved model state variables and parameters. Ideally, these inference algorithms should find the best fitting solution for a given model and set of observations; however, as those estimated quantities are unobserved, it is typically uncertain whether the correct parameters have been identified. Further, it is unclear what 'correct' really means for abstract parameters defined based on specific model forms. In this work, we explored the problem of non-identifiability in a stochastic system which, when overlooked, can significantly impede model prediction. We used a network, agent-based model to simulate the transmission of Methicillin-resistant staphylococcus aureus (MRSA) within hospital settings and attempted to infer key model parameters using the Ensemble Adjustment Kalman Filter, an efficient Bayesian inference algorithm. We show that even though the inference method converged and that simulations using the estimated parameters produced an agreement with observations, the true parameters are not fully identifiable. While the model-inference system can exclude a substantial area of parameter space that is unlikely to contain the true parameters, the estimated parameter range still included multiple parameter combinations that can fit observations equally well. We show that analyzing synthetic trajectories can support or contradict claims of identifiability. While we perform this on a specific model system, this approach can be generalized for a variety of stochastic representations of partially observable systems. We also suggest data manipulations intended to improve identifiability that might be applicable in many systems of interest.

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.

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.

Evaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty.

Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections.

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.

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.

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.

Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub.

Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.

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.

The impact of COVID-19 vaccination in the US: Averted burden of SARS-COV-2-related cases, hospitalizations and deaths.

By August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.

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.

Trends in Crisis Hotline Call Rates and Suicide Mortality in the United States.

OBJECTIVE: Utilization of the 988 Suicide and Crisis Lifeline (Lifeline; formerly called the National Suicide Prevention Lifeline) was analyzed in relation to suicide deaths in U.S. states between 2007 and 2020 to identify states with potential unmet need for mental health crisis hotline services. METHODS: Annual state call rates were calculated from calls routed to the Lifeline during the 2007-2020 period (N=13.6 million). Annual state suicide mortality rates (standardized) were calculated from suicide deaths reported to the National Vital Statistics System (2007-2020 cumulative deaths=588,122). Call rate ratio (CRR) and mortality rate ratio (MRR) were estimated by state and year. RESULTS: Sixteen U.S. states demonstrated a consistently high MRR and a low CRR, suggesting high suicide burden and relatively low Lifeline use. Heterogeneity in state CRRs decreased over time. CONCLUSIONS: Prioritizing states with a high MRR and a low CRR for messaging and outreach regarding the availability of the Lifeline can ensure more equitable, need-based access to this critical resource.

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.