Generative Bayesian modeling to nowcast the effective reproduction number from line list data with missing symptom onset dates.

The time-varying effective reproduction number Rt is a widely used indicator of transmission dynamics during infectious disease outbreaks. Timely estimates of Rt can be obtained from reported cases counted by their date of symptom onset, which is generally closer to the time of infection than the date of report. Case counts by date of symptom onset are typically obtained from line list data, however these data can have missing information and are subject to right truncation. Previous methods have addressed these problems independently by first imputing missing onset dates, then adjusting truncated case counts, and finally estimating the effective reproduction number. This stepwise approach makes it difficult to propagate uncertainty and can introduce subtle biases during real-time estimation due to the continued impact of assumptions made in previous steps. In this work, we integrate imputation, truncation adjustment, and Rt estimation into a single generative Bayesian model, allowing direct joint inference of case counts and Rt from line list data with missing symptom onset dates. We then use this framework to compare the performance of nowcasting approaches with different stepwise and generative components on synthetic line list data for multiple outbreak scenarios and across different epidemic phases. We find that under reporting delays realistic for hospitalization data (50% of reports delayed by more than a week), intermediate smoothing, as is common practice in stepwise approaches, can bias nowcasts of case counts and Rt, which is avoided in a joint generative approach due to shared regularization of all model components. On incomplete line list data, a fully generative approach enables the quantification of uncertainty due to missing onset dates without the need for an initial multiple imputation step. In a real-world comparison using hospitalization line list data from the COVID-19 pandemic in Switzerland, we observe the same qualitative differences between approaches. The generative modeling components developed in this work have been integrated and further extended in the R package epinowcast, providing a flexible and interpretable tool for real-time surveillance.

Best practices for estimating and reporting epidemiological delay distributions of infectious diseases.

Epidemiological delays are key quantities that inform public health policy and clinical practice. They are used as inputs for mathematical and statistical models, which in turn can guide control strategies. In recent work, we found that censoring, right truncation, and dynamical bias were rarely addressed correctly when estimating delays and that these biases were large enough to have knock-on impacts across a large number of use cases. Here, we formulate a checklist of best practices for estimating and reporting epidemiological delays. We also provide a flowchart to guide practitioners based on their data. Our examples are focused on the incubation period and serial interval due to their importance in outbreak response and modeling, but our recommendations are applicable to other delays. The recommendations, which are based on the literature and our experience estimating epidemiological delay distributions during outbreak responses, can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.

estimateR: an R package to estimate and monitor the effective reproductive number.

BACKGROUND: Accurate estimation of the effective reproductive number ([Formula: see text]) of epidemic outbreaks is of central relevance to public health policy and decision making. We present estimateR, an R package for the estimation of the reproductive number through time from delayed observations of infection events. Such delayed observations include confirmed cases, hospitalizations or deaths. The package implements the methodology of Huisman et al. but modularizes the [Formula: see text] estimation procedure to allow easy implementation of new alternatives to the currently available methods. Users can tailor their analyses according to their particular use case by choosing among implemented options. RESULTS: The estimateR R package allows users to estimate the effective reproductive number of an epidemic outbreak based on observed cases, hospitalization, death or any other type of event documenting past infections, in a fast and timely fashion. We validated the implementation with a simulation study: estimateR yielded estimates comparable to alternative publicly available methods while being around two orders of magnitude faster. We then applied estimateR to empirical case-confirmation incidence data for COVID-19 in nine countries and for dengue fever in Brazil; in parallel, estimateR is already being applied (i) to SARS-CoV-2 measurements in wastewater data and (ii) to study influenza transmission based on wastewater and clinical data in other studies. In summary, this R package provides a fast and flexible implementation to estimate the effective reproductive number for various diseases and datasets. CONCLUSIONS: The estimateR R package is a modular and extendable tool designed for outbreak surveillance and retrospective outbreak investigation. It extends the method developed for COVID-19 by Huisman et al. and makes it available for a variety of pathogens, outbreak scenarios, and observation types. Estimates obtained with estimateR can be interpreted directly or used to inform more complex epidemic models (e.g. for forecasting) on the value of [Formula: see text].

The methodologies to assess the effectiveness of non-pharmaceutical interventions during COVID-19: a systematic review.

Non-pharmaceutical interventions, such as school closures and stay-at-home orders, have been implemented around the world to control the spread of SARS-CoV-2. Their effectiveness in improving health-related outcomes has been the subject of numerous empirical studies. However, these studies show fairly large variation among methodologies in use, reflecting the absence of an established methodological framework. On the one hand, variation in methodologies may be desirable to assess the robustness of results; on the other hand, a lack of common standards can impede comparability among studies. To establish a comprehensive overview over the methodologies in use, we conducted a systematic review of studies assessing the effectiveness of non-pharmaceutical interventions between January 1, 2020 and January 12, 2021 (n = 248). We identified substantial variation in methodologies with respect to study setting, outcome, intervention, methodological approach, and effectiveness assessment. On this basis, we point to shortcomings of existing studies and make recommendations for the design of future studies.

Estimating the effect of mobility on SARS-CoV-2 transmission during the first and second wave of the COVID-19 epidemic, Switzerland, March to December 2020.

IntroductionHuman mobility was considerably reduced during the COVID-19 pandemic. To support disease surveillance, it is important to understand the effect of mobility on transmission.AimWe compared the role of mobility during the first and second COVID-19 wave in Switzerland by studying the link between daily travel distances and the effective reproduction number (Rt) of SARS-CoV-2.MethodsWe used aggregated mobile phone data from a representative panel survey of the Swiss population to measure human mobility. We estimated the effects of reductions in daily travel distance on Rt via a regression model. We compared mobility effects between the first (2 March-7 April 2020) and second wave (1 October-10 December 2020).ResultsDaily travel distances decreased by 73% in the first and by 44% in the second wave (relative to February 2020). For a 1% reduction in average daily travel distance, Rt was estimated to decline by 0.73% (95% credible interval (CrI): 0.34-1.03) in the first wave and by 1.04% (95% CrI: 0.66-1.42) in the second wave. The estimated mobility effects were similar in both waves for all modes of transport, travel purposes and sociodemographic subgroups but differed for movement radius.ConclusionMobility was associated with SARS-CoV-2 Rt during the first two epidemic waves in Switzerland. The relative effect of mobility was similar in both waves, but smaller mobility reductions in the second wave corresponded to smaller overall reductions in Rt. Mobility data from mobile phones have a continued potential to support real-time surveillance of COVID-19.

Effectiveness assessment of non-pharmaceutical interventions: lessons learned from the COVID-19 pandemic.

Effectiveness of non-pharmaceutical interventions (NPIs), such as school closures and stay-at-home orders, during the COVID-19 pandemic has been assessed in many studies. Such assessments can inform public health policies and contribute to evidence-based choices of NPIs during subsequent waves or future epidemics. However, methodological issues and no standardised assessment practices have restricted the practical value of the existing evidence. Here, we present and discuss lessons learned from the COVID-19 pandemic and make recommendations for standardising and improving assessment, data collection, and modelling. These recommendations could contribute to reliable and policy-relevant assessments of the effectiveness of NPIs during future epidemics.

A Scalable Risk-Scoring System Based on Consumer-Grade Wearables for Inpatients With COVID-19: Statistical Analysis and Model Development.

BACKGROUND: To provide effective care for inpatients with COVID-19, clinical practitioners need systems that monitor patient health and subsequently allow for risk scoring. Existing approaches for risk scoring in patients with COVID-19 focus primarily on intensive care units (ICUs) with specialized medical measurement devices but not on hospital general wards. OBJECTIVE: In this paper, we aim to develop a risk score for inpatients with COVID-19 in general wards based on consumer-grade wearables (smartwatches). METHODS: Patients wore consumer-grade wearables to record physiological measurements, such as the heart rate (HR), heart rate variability (HRV), and respiration frequency (RF). Based on Bayesian survival analysis, we validated the association between these measurements and patient outcomes (ie, discharge or ICU admission). To build our risk score, we generated a low-dimensional representation of the physiological features. Subsequently, a pooled ordinal regression with time-dependent covariates inferred the probability of either hospital discharge or ICU admission. We evaluated the predictive performance of our developed system for risk scoring in a single-center, prospective study based on 40 inpatients with COVID-19 in a general ward of a tertiary referral center in Switzerland. RESULTS: First, Bayesian survival analysis showed that physiological measurements from consumer-grade wearables are significantly associated with patient outcomes (ie, discharge or ICU admission). Second, our risk score achieved a time-dependent area under the receiver operating characteristic curve (AUROC) of 0.73-0.90 based on leave-one-subject-out cross-validation. CONCLUSIONS: Our results demonstrate the effectiveness of consumer-grade wearables for risk scoring in inpatients with COVID-19. Due to their low cost and ease of use, consumer-grade wearables could enable a scalable monitoring system. TRIAL REGISTRATION: Clinicaltrials.gov NCT04357834; https://www.clinicaltrials.gov/ct2/show/NCT04357834.

Estimating the effects of non-pharmaceutical interventions on the number of new infections with COVID-19 during the first epidemic wave.

The novel coronavirus (SARS-CoV-2) has rapidly developed into a global epidemic. To control its spread, countries have implemented non-pharmaceutical interventions (NPIs), such as school closures, bans of small gatherings, or even stay-at-home orders. Here we study the effectiveness of seven NPIs in reducing the number of new infections, which was inferred from the reported cases of COVID-19 using a semi-mechanistic Bayesian hierarchical model. Based on data from the first epidemic wave of n = 20 countries (i.e., the United States, Canada, Australia, the EU-15 countries, Norway, and Switzerland), we estimate the relative reduction in the number of new infections attributed to each NPI. Among the NPIs considered, bans of large gatherings were most effective, followed by venue and school closures, whereas stay-at-home orders and work-from-home orders were least effective. With this retrospective cross-country analysis, we provide estimates regarding the effectiveness of different NPIs during the first epidemic wave.