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      Inferring the effective reproductive number from deterministic and semi-deterministic compartmental models using incidence and mobility data

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      PLoS Computational Biology
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          Abstract

          The effective reproduction number (ℜ t ) is a theoretical indicator of the course of an infectious disease that allows policymakers to evaluate whether current or previous control efforts have been successful or whether additional interventions are necessary. This metric, however, cannot be directly observed and must be inferred from available data. One approach to obtaining such estimates is fitting compartmental models to incidence data. We can envision these dynamic models as the ensemble of structures that describe the disease’s natural history and individuals’ behavioural patterns. In the context of the response to the COVID-19 pandemic, the assumption of a constant transmission rate is rendered unrealistic, and it is critical to identify a mathematical formulation that accounts for changes in contact patterns. In this work, we leverage existing approaches to propose three complementary formulations that yield similar estimates for ℜ t based on data from Ireland’s first COVID-19 wave. We describe these Data Generating Processes (DGP) in terms of State-Space models. Two (DGP1 and DGP2) correspond to stochastic process models whose transmission rate is modelled as Brownian motion processes (Geometric and Cox-Ingersoll-Ross). These DGPs share a measurement model that accounts for incidence and transmission rates, where mobility data is assumed as a proxy of the transmission rate. We perform inference on these structures using Iterated Filtering and the Particle Filter. The final DGP (DGP3) is built from a pool of deterministic models that describe the transmission rate as information delays. We calibrate this pool of models to incidence reports using Hamiltonian Monte Carlo. By following this complementary approach, we assess the tradeoffs associated with each formulation and reflect on the benefits/risks of incorporating proxy data into the inference process. We anticipate this work will help evaluate the implications of choosing a particular formulation for the dynamics and observation of the time-varying transmission rate.

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          Policymakers use the effective reproduction number (ℜ t ) to determine whether an epidemic is growing (ℜ t > 1) or shrinking (ℜ t < 1). One can estimate this quantity by simulating compartmental models fitted to data. These models can be seen as the ensemble of two structures: one that describes the course of a disease in an individual and another one that accounts for behavioural patterns. Nevertheless, these estimates are sensitive to the assumptions embedded in the model, such as the formulation of the time-varying transmission rate. In this paper, we couple an SEIR-type structure with three complementary formulations: 1) non-negative random-walks (Geometric Brownian Motion) 2) non-negative random-walks pulled toward a long-term goal (Cox-Ingersoll-Ross) 3) Gradual approximations towards a long-term goal (exponential smoothing). We refer to each coupling as a Data Generating Process (DGP). In essence, we simulate trajectories from these DGPs to identify plausible sets of transmission rates (based on incidence and mobility data) that explain Ireland’s first COVID-19 wave. Here, we assume that mobility data is a proxy measurement for the transmission rate. These DGPs yield similar average estimates for ℜ t , albeit with dissimilar degrees of uncertainty. Finally, we reflect on the tradeoffs of choosing each particular formulation.

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          Most cited references59

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          Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

          Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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            Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe

            Following the detection of the new coronavirus1 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics of coronavirus disease 2019 (COVID-19). In response, many European countries have implemented non-pharmaceutical interventions, such as the closure of schools and national lockdowns. Here we study the effect of major interventions across 11 European countries for the period from the start of the COVID-19 epidemics in February 2020 until 4 May 2020, when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks previously, allowing for the time lag between infection and death. We use partial pooling of information between countries, with both individual and shared effects on the time-varying reproduction number (Rt). Pooling allows for more information to be used, helps to overcome idiosyncrasies in the data and enables more-timely estimates. Our model relies on fixed estimates of some epidemiological parameters (such as the infection fatality rate), does not include importation or subnational variation and assumes that changes in Rt are an immediate response to interventions rather than gradual changes in behaviour. Amidst the ongoing pandemic, we rely on death data that are incomplete, show systematic biases in reporting and are subject to future consolidation. We estimate that-for all of the countries we consider here-current interventions have been sufficient to drive Rt below 1 (probability Rt < 1.0 is greater than 99%) and achieve control of the epidemic. We estimate that across all 11 countries combined, between 12 and 15 million individuals were infected with SARS-CoV-2 up to 4 May 2020, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions-and lockdowns in particular-have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.
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              Stan: A Probabilistic Programming Language

              Stan is a probabilistic programming language for specifying statistical models. A Stan program imperatively defines a log probability function over parameters conditioned on specified data and constants. As of version 2.14.0, Stan provides full Bayesian inference for continuous-variable models through Markov chain Monte Carlo methods such as the No-U-Turn sampler, an adaptive form of Hamiltonian Monte Carlo sampling. Penalized maximum likelihood estimates are calculated using optimization methods such as the limited memory Broyden-Fletcher-Goldfarb-Shanno algorithm. Stan is also a platform for computing log densities and their gradients and Hessians, which can be used in alternative algorithms such as variational Bayes, expectation propagation, and marginal inference using approximate integration. To this end, Stan is set up so that the densities, gradients, and Hessians, along with intermediate quantities of the algorithm such as acceptance probabilities, are easily accessible. Stan can be called from the command line using the cmdstan package, through R using the rstan package, and through Python using the pystan package. All three interfaces support sampling and optimization-based inference with diagnostics and posterior analysis. rstan and pystan also provide access to log probabilities, gradients, Hessians, parameter transforms, and specialized plotting.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Comput Biol
                PLoS Comput Biol
                plos
                PLoS Computational Biology
                Public Library of Science (San Francisco, CA USA )
                1553-734X
                1553-7358
                June 2022
                27 June 2022
                : 18
                : 6
                : e1010206
                Affiliations
                [1 ] Data Science Institute and School of Computer Science, National University of Ireland Galway, Ireland
                [2 ] School of Computer Science, Ryan Institute and Data Science Institute, National University of Ireland Galway, Ireland
                University of Washington, UNITED STATES
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: 1. Prof. Jim Duggan is a member of the WHO Global Outbreak and Response Network (GOARN), through the involvement of the National University of Ireland Galway as a GOARN partner. (NGO) 2. Prof. Jim Duggan is a member of the Irish Epidemiological Modelling Advisory Group (IEMAG), and in this volunteering role, provides modelling advice to the Department of Health, Ireland. Also, the work presented is independent of (1) and has only benefited from an aggregated data set received from (2).

                Author information
                https://orcid.org/0000-0002-1412-7868
                https://orcid.org/0000-0002-7507-8617
                Article
                PCOMPBIOL-D-21-01788
                10.1371/journal.pcbi.1010206
                9269962
                35759506
                3fb37c3e-04ca-42a8-9a39-92c29c508df8
                © 2022 Andrade, Duggan

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 October 2021
                : 11 May 2022
                Page count
                Figures: 7, Tables: 1, Pages: 25
                Funding
                Funded by: H2020 research and innovation programme
                Award ID: 883285
                The project has received funding –through the School of Medicine, National University of Ireland Galway– from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 883285. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Covid 19
                Medicine and Health Sciences
                Epidemiology
                People and places
                Geographical locations
                Europe
                European Union
                Ireland
                Medicine and Health Sciences
                Epidemiology
                Pandemics
                Physical Sciences
                Physics
                Classical Mechanics
                Continuum Mechanics
                Fluid Mechanics
                Fluid Dynamics
                Brownian Motion
                Physical Sciences
                Mathematics
                Probability Theory
                Stochastic Processes
                Brownian Motion
                Research and Analysis Methods
                Simulation and Modeling
                Medicine and Health Sciences
                Diagnostic Medicine
                Virus Testing
                Physical Sciences
                Mathematics
                Probability Theory
                Probability Distribution
                Custom metadata
                vor-update-to-uncorrected-proof
                2022-07-08
                All relevant data are within the paper and its Supporting information files. The code is available on GitHub at https://github.com/jandraor/time_varying_beta.

                Quantitative & Systems biology
                Quantitative & Systems biology

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