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COVID-19 forecasting models have been critical in guiding decision-making on surveillance testing, social distancing, and vaccination requirements. Beyond influencing public health policies, an accurate COVID-19 forecasting model can impact community spread by enabling employers and university leaders to adapt worksite policies and practices to contain or mitigate outbreaks. While many such models have been developed for COVID-19 forecasting at the national, state, county, or city level, only a few models have been developed for workplaces and universities. Furthermore, COVID-19 forecasting models have rarely been validated against real COVID-19 case data. Here we present the systematic parameter fitting and validation of an agent-based compartment model for the forecasting of daily COVID-19 cases in single-site workplaces and universities with real-world data. Our approaches include manual fitting, where initial model parameters are chosen based on historical data, and automated fitting, where parameters are chosen based on candidate case trajectory simulations that result in best fit to prevalence estimation data. We use a 14-day fitting window and validate our approaches on 7- and 14-day testing windows with real COVID-19 case data from one employer. Our manual and automated fitting approaches accurately predicted COVID-19 case trends and outperformed the baseline model (no parameter fitting) across multiple scenarios, including a rising case trajectory (RMSLE values: 2.627 for baseline, 0.562 for manual fitting, 0.399 for automated fitting) and a decreasing case trajectory (RMSLE values: 1.155 for baseline, 0.537 for manual fitting, 0.778 for automated fitting). Our COVID-19 case forecasting model allows decision-makers at workplaces and universities to proactively respond to case trend forecasts, mitigate outbreaks, and promote safety.

As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educational institutions in a manner that is safe, ethical, grounded in science, and takes into account the unique factors and needs of each organization and community. In this paper, we introduce an epidemiological model (the “Community-Workplace” model) that accounts for SARS-CoV-2 transmission within the workplace, within the surrounding community, and between them. We use this multi-group deterministic compartmental model to consider various testing strategies that, together with symptom screening, exposure tracking, and nonpharmaceutical interventions (NPI) such as mask wearing and physical distancing, aim to reduce disease spread in the workplace. Our framework is designed to be adaptable to a variety of specific workplace environments to support planning efforts as reopenings continue. Using this model, we consider a number of case studies, including an office workplace, a factory floor, and a university campus. Analysis of these cases illustrates that continuous testing can help a workplace avoid an outbreak by reducing undetected infectiousness even in high-contact environments. We find that a university setting, where individuals spend more time on campus and have a higher contact load, requires more testing to remain safe, compared to a factory or office setting. Under the modeling assumptions, we find that maintaining a prevalence below 3% can be achieved in an office setting by testing its workforce every two weeks, whereas achieving this same goal for a university could require as much as fourfold more testing (i.e., testing the entire campus population twice a week). Our model also simulates the dynamics of reduced spread that result from the introduction of mitigation measures when test results reveal the early stages of a workplace outbreak. We use this to show that a vigilant university that has the ability to quickly react to outbreaks can be justified in implementing testing at the same rate as a lower-risk office workplace. Finally, we quantify the devastating impact that an outbreak in a small-town college could have on the surrounding community, which supports the notion that communities can be better protected by supporting their local places of business in preventing onsite spread of disease.

Clinical sleep evaluations currently require multimodal data collection and manual review by human experts, making them expensive and unsuitable for longer term studies. Sleep staging using cardiac rhythm is an active area of research because it can be measured much more easily using a wide variety of both medical and consumer-grade devices. In this study, we applied deep learning methods to create an algorithm for automated sleep stage scoring using the instantaneous heart rate (IHR) time series extracted from the electrocardiogram (ECG). We trained and validated an algorithm on over 10,000 nights of data from the Sleep Heart Health Study (SHHS) and Multi-Ethnic Study of Atherosclerosis (MESA). The algorithm has an overall performance of 0.77 accuracy and 0.66 kappa against the reference stages on a held-out portion of the SHHS dataset for classifying every 30 s of sleep into four classes: wake, light sleep, deep sleep, and rapid eye movement (REM). Moreover, we demonstrate that the algorithm generalizes well to an independent dataset of 993 subjects labeled by American Academy of Sleep Medicine (AASM) licensed clinical staff at Massachusetts General Hospital that was not used for training or validation. Finally, we demonstrate that the stages predicted by our algorithm can reproduce previous clinical studies correlating sleep stages with comorbidities such as sleep apnea and hypertension as well as demographics such as age and gender.

Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules. Paradoxically, the pneumococcal capsule sensitizes the bacterium to antimicrobial peptides found on epithelial surfaces. Here we show that upon interaction with antimicrobial peptides, encapsulated pneumococci survive by removing capsule from the cell surface within minutes in a process dependent on the suicidal amidase autolysin LytA. In contrast to classical bacterial autolysis, during capsule shedding, LytA promotes bacterial survival and is dispersed circumferentially around the cell. However, both autolysis and capsule shedding depend on the cell wall hydrolytic activity of LytA. Capsule shedding drastically increases invasion of epithelial cells and is the main pathway by which pneumococci reduce surface bound capsule during early acute lung infection of mice. The previously unrecognized role of LytA in removing capsule to combat antimicrobial peptides may explain why nearly all clinical isolates of pneumococci conserve this enzyme despite the lethal selective pressure of antibiotics. Pneumococci produce a carbohydrate capsule that protects them against components of the host immune system but sensitizes them to host antimicrobial peptides. Here, Kietzman et al. show that pneumococci respond to antimicrobial peptides by capsule shedding, which requires the main autolysin LytA.

Sensor-based remote monitoring could help better track Parkinson’s disease (PD) progression, and measure patients’ response to putative disease-modifying therapeutic interventions. To be useful, the remotely-collected measurements should be valid, reliable, and sensitive to change, and people with PD must engage with the technology. We developed a smartwatch-based active assessment that enables unsupervised measurement of motor signs of PD. Participants with early-stage PD ( N  = 388, 64% men, average age 63) wore a smartwatch for a median of 390 days. Participants performed unsupervised motor tasks both in-clinic (once) and remotely (twice weekly for one year). Dropout rate was 5.4%. Median wear-time was 21.1 h/day, and 59% of per-protocol remote assessments were completed. Analytical validation was established for in-clinic measurements, which showed moderate-to-strong correlations with consensus MDS-UPDRS Part III ratings for rest tremor (⍴ = 0.70), bradykinesia (⍴ = −0.62), and gait (⍴ = −0.46). Test-retest reliability of remote measurements, aggregated monthly, was good-to-excellent (ICC = 0.75–0.96). Remote measurements were sensitive to the known effects of dopaminergic medication (on vs off Cohen’s d = 0.19–0.54). Of note, in-clinic assessments often did not reflect the patients’ typical status at home. This demonstrates the feasibility of smartwatch-based unsupervised active tests, and establishes the analytical validity of associated digital measurements. Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally. Sensitivity to medication-induced change and improved reliability imply that these methods could help reduce sample sizes needed to demonstrate a response to therapeutic interventions or disease progression.

Background: Although effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, and scalable way to capture real-world data from patients that could augment clinical decision-making and move the field of mental health closer to measurement-based care. Objective: This study tests the feasibility of a fully remote study on individuals with self-reported depression using an Android-based smartphone app to collect subjective and objective measures associated with depression severity. The goals of this pilot study are to develop an engaging user interface for high task adherence through user-centered design; test the quality of collected data from passive sensors; start building clinically relevant behavioral measures (features) from passive sensors and active inputs; and preliminarily explore connections between these features and depression severity. Methods: A total of 600 participants were asked to download the study app to join this fully remote, observational 12-week study. The app passively collected 20 sensor data streams (eg, ambient audio level, location, and inertial measurement units), and participants were asked to complete daily survey tasks, weekly voice diaries, and the clinically validated Patient Health Questionnaire (PHQ-9) self-survey. Pairwise correlations between derived behavioral features (eg, weekly minutes spent at home) and PHQ-9 were computed. Using these behavioral features, we also constructed an elastic net penalized multivariate logistic regression model predicting depressed versus nondepressed PHQ-9 scores (ie, dichotomized PHQ-9). Results: A total of 415 individuals logged into the app. Over the course of the 12-week study, these participants completed 83.35% (4151/4980) of the PHQ-9s. Applying data sufficiency rules for minimally necessary daily and weekly data resulted in 3779 participant-weeks of data across 384 participants. Using a subset of 34 behavioral features, we found that 11 features showed a significant (P<.001 Benjamini-Hochberg adjusted) Spearman correlation with weekly PHQ-9, including voice diary–derived word sentiment and ambient audio levels. Restricting the data to those cases in which all 34 behavioral features were present, we had available 1013 participant-weeks from 186 participants. The logistic regression model predicting depression status resulted in a 10-fold cross-validated mean area under the curve of 0.656 (SD 0.079). Conclusions: This study finds a strong proof of concept for the use of a smartphone-based assessment of depression outcomes. Behavioral features derived from passive sensors and active tasks show promising correlations with a validated clinical measure of depression (PHQ-9). Future work is needed to increase scale that may permit the construction of more complex (eg, nonlinear) predictive models and better handle data missingness.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Introduction Heart rate is well-known to be modulated by sleep stages. If clinically useful sleep scoring can be performed using only cardiac rhythms, then existing medical and consumer-grade devices that can measure heart rate can enable low-cost sleep evaluations. Methods We trained a neural network which uses dilated convolutional blocks to learn both local and long range features of heart rate extracted from ECG R-wave timing to predict for every non-overlapping 30s epoch of the input the probabilities of the epoch being in one of four classes—wake, light sleep, deep sleep or REM. The largest probability is chosen as the network’s class prediction and used to form the hypnogram. We used the Sleep Heart Health Study (SHHS) and Multi-Ethnic Study of Atherosclerosis Study (MESA) and Physionet Computing in Cardiology (CinC) dataset (over 10000 nights) for training and evaluation. Then we deployed the algorithm on PPG based heart rate measured by a wrist-worn device worn by subjects in a free-living setting. Results On the held out test SHHS dataset (800 nights, 561 subjects), the overall 4-class staging accuracy was 77% and Cohen’s kappa was 0.66. On the CinC dataset (993 nights, 993 subjects), the overall 4 class accuracy was 72% and Cohen’s kappa was 0.55. The study on free-living subjects is underway and these novel results will be collated and presented upon completion. Conclusion We hope these results build more trust in automated heart rate based sleep staging and encourage further research into its clinical application in screening and diagnosis of sleep disorders. Low cost, high efficacy devices which can be used in longitudinal studies can lead to breakthroughs in clinical applications of sleep staging for early diagnosis of chronic conditions and novel treatment endpoints. Support (if any) We recently published the training/testing of the algorithm as well a population level analysis showing differences in predicted sleep stages between disease cohorts. The article was published in NPJ Digital Medicine in Aug 2020. The study on free living subjects is currently underway and these new results will be presented at the sleep conference. Preliminary results indicate high concordance with our published results.