Dynamic Causal Modelling of COVID-19

Dynamic causal modelling of COVID-19. By Karl J. Friston, Thomas Parr, Peter Zeidman, Adeel Razi, Guillaume Flandin, Jean Daunizeau, Oliver J. Hulme, Alexander J. Billig, Vladimir Litvak, Rosalyn J. Moran, Cathy J. Price, Christian Lambert. This technical report describes a dynamic causal model of the spread of coronavirus through a population. The model is based upon ensemble or population dynamics that generate outcomes, like new cases and deaths over time. The purpose of this model is to quantify the uncertainty that attends predictions of relevant outcomes. By assuming suitable conditional dependencies, one can model the effects of interventions (e.g., social distancing) and differences among populations (e.g., herd immunity) to predict what might happen in different circumstances. Technically, this model leverages state-of-the-art variational (Bayesian) model inversion and comparison procedures, originally developed to characterise the responses of neuronal ensembles to perturbations. Here, this modelling is applied to epidemiological populations - to illustrate the kind of inferences that are supported and how the model per se can be optimised given timeseries data. Although the purpose of this paper is to describe a modelling protocol, the results illustrate some interesting perspectives on the current pandemic; for example, the nonlinear effects of herd immunity that speak to a self-organised mitigation process.

This technical report was prepared as a proof of concept for submission to the SPI-M (Scientific Pandemic Influenza Group on Modelling) and the RAMP (Rapid Assistance in Modelling the Pandemic) initiative.

Preprint available on arXiv, article published in Wellcome Open Research and software available in SPM.

Blogpost on the term "immunological dark matter" (June 2020).

Group meeting on Tuesday 7th April 2020 with a presentation (slides) from Professor Karl Friston.

Second waves, social distancing, and the spread of COVID-19 across America. By Karl J. Friston, Thomas Parr, Peter Zeidman, Adeel Razi, Guillaume Flandin, Jean Daunizeau, Oliver J. Hulme, Alexander J. Billig, Vladimir Litvak, Rosalyn J. Moran, Cathy J. Price, Christian Lambert. We recently described a dynamic causal model of a COVID-19 outbreak within a single region. Here, we combine several of these (epidemic) models to create a (pandemic) model of viral spread among regions. Our focus is on a second wave of new cases that may result from loss of immunity--and the exchange of people between regions--and how mortality rates can be ameliorated under different strategic responses. In particular, we consider hard or soft social distancing strategies predicated on national (Federal) or regional (State) estimates of the prevalence of infection in the population. The modelling is demonstrated using timeseries of new cases and deaths from the United States to estimate the parameters of a factorial (compartmental) epidemiological model of each State and, crucially, coupling between States. Using Bayesian model reduction, we identify the effective connectivity between States that best explains the initial phases of the outbreak in the United States. Using the ensuing posterior parameter estimates, we then evaluate the likely outcomes of different policies in terms of mortality, working days lost due to lockdown and demands upon critical care. The provisional results of this modelling suggest that social distancing and loss of immunity are the two key factors that underwrite a return to endemic equilibrium.

Preprint available on arXiv, article published in Wellcome Open Research and software available in SPM.

Brain meeting on Friday 24th April 2020 with a presentation (slides) from Professor Karl Friston.

Testing and tracking in the UK: a dynamic causal modelling study. By Karl J. Friston, Thomas Parr, Peter Zeidman, Adeel Razi, Guillaume Flandin, Jean Daunizeau, Oliver J. Hulme, Alexander J. Billig, Vladimir Litvak, Rosalyn J. Moran, Cathy J. Price, Christian Lambert. By equipping a previously reported dynamic causal model of COVID-19 with an isolation state, we modelled the effects of self-isolation consequent on tracking and tracing. Specifically, we included a quarantine or isolation state occupied by people who believe they might be infected but are asymptomatic, and only leave if they test negative. We recovered maximum posteriori estimates of the model parameters using time series of new cases, daily deaths, and tests for the UK. These parameters were used to simulate the trajectory of the outbreak in the UK over an 18-month period. Several clear-cut conclusions emerged from these simulations. For example, under plausible (graded) relaxations of social distancing, a rebound of infections within weeks is unlikely. The emergence of a later second wave depends almost exclusively on the rate at which we lose immunity, inherited from the first wave. There exists no testing strategy that can attenuate mortality rates, other than by deferring or delaying a second wave. A sufficiently powerful tracking and tracing policy - implemented at the time of writing (10th May 2020) - will defer any second wave beyond a time horizon of 18 months. Crucially, this deferment is within current testing capabilities (requiring an efficacy of tracing and tracking of about 20% of asymptomatic infected cases, with less than 50,000 tests per day). These conclusions are based upon a dynamic causal model for which we provide some construct and face validation, using a comparative analysis of the United Kingdom and Germany, supplemented with recent serological studies.

Preprint available on arXiv, article published in Wellcome Open Research and software in SPM.

Effective immunity and second waves: a dynamic causal modelling study. By Karl J. Friston, Thomas Parr, Peter Zeidman, Adeel Razi, Guillaume Flandin, Jean Daunizeau, Oliver J. Hulme, Alexander J. Billig, Vladimir Litvak, Cathy J. Price, Rosalyn J. Moran, Anthony Costello, Deenan Pillay, Christian Lambert. This technical report addresses a pressing issue in the trajectory of the coronavirus outbreak; namely, the rate at which effective immunity is lost following the first wave of the pandemic. This is a crucial epidemiological parameter that speaks to both the consequences of relaxing lockdown and the propensity for a second wave of infections. Using a dynamic causal model of reported cases and deaths from multiple countries, we evaluated the evidence models of progressively longer periods of immunity. The results speak to an effective population immunity of about three months that, under the model, defers any second wave for approximately six months in most countries. This may have implications for the window of opportunity for tracking and tracing, as well as for developing vaccination programmes, and other therapeutic interventions.

Preprint available on arXiv, article published in Wellcome Open Research and software in SPM.

What causes second waves? By Karl J. Friston and Alexander J. Billig. This report uses dynamic causal modelling of daily cases and deaths to distinguish between secondary and second waves, in terms of the underlying mechanisms and associated mortality due to SARS-CoV-2. Here, secondary waves are taken to reflect a spread of the virus through the population, reaching previously unexposed communities after the first wave has peaked. Conversely, second waves refer to the reinfection of a previously exposed population, due to a loss of effective (population) immunity. Our quantitative modelling suggests that the fatality rates that accompany both secondary and second waves are substantially less than the first wave - and an order of magnitude less than predictions based upon prevalent epidemiological models that ignore heterogeneity in viral exposure, susceptibility and transmission.

Internal report

Dark matter, second waves and epidemiological modelling. By Karl J. Friston, Anthony Costello, Deenan Pillay. Recent reports based on conventional SEIR models suggest that the next wave of the COVID-19 pandemic in the UK could overwhelm health services, with fatalities that far exceed the first wave. These models suggest non-pharmaceutical interventions would have limited impact without intermittent national lockdowns and consequent economic and health impacts. We used Bayesian model comparison to revisit these conclusions, when allowing for heterogeneity of exposure, susceptibility, and viral transmission. We used dynamic causal modelling to estimate the parameters of epidemiological models and, crucially, the evidence for alternative models of the same data. We compared SEIR models of immune status that were equipped with latent factors generating data; namely, location, symptom, and testing status. We analysed daily cases and deaths from the US, UK, Brazil, Italy, France, Spain, Mexico, Belgium, Germany, and Canada over the period 25-Jan-20 to 15-Jun-20. These data were used to estimate the composition of each country's population in terms of the proportions of people (i) not exposed to the virus, (ii) not susceptible to infection when exposed, and (iii) not infectious when susceptible to infection. Findings Bayesian model comparison found overwhelming evidence for heterogeneity of exposure, susceptibility, and transmission. Furthermore, both lockdown and the build-up of population immunity contributed to viral transmission in all but one country. Small variations in heterogeneity were sufficient to explain the large differences in mortality rates across countries. The best model of UK data predicts a second surge of fatalities will be much less than the first peak (31 vs. 998 deaths per day. 95% CI: 24-37) - substantially less than conventional model predictions. The size of the second wave depends sensitively upon the loss of immunity and the efficacy of find-test-trace-isolate-support (FTTIS) programmes. Interpretation A dynamic causal model that incorporates heterogeneity of exposure, susceptibility and transmission suggests that the next wave of the SARS-CoV-2 pandemic will be much smaller than conventional models predict, with less economic and health disruption. This heterogeneity means that seroprevalence underestimates effective herd immunity and, crucially, the potential of public health programmes.

Preprint available on medRxiv

Related work

Estimating required 'lockdown' cycles before immunity to SARS-CoV-2: Model-based analyses of susceptible population sizes, 'S0', in seven European countries including the UK and Ireland. By Rosalyn J. Moran, Erik D. Fagerholm, Maell Cullen, Jean Daunizeau, Mark P. Richardson, Steven Williams, Federico Turkheimer, Rob Leech, Karl J. Friston.

Preprint available on arXiv and software on GitHub.

On the reliability of model-based predictions in the context of the current COVID epidemic event: impact of outbreak peak phase and data paucity. By Jean Daunizeau, Rosalyn J. Moran, Jérémie Mattout, Karl J. Friston.

Preprint available on medRxiv and software on GitHub.

Using the LIST model to Estimate the Effects of Contact Tracing on COVID-19 Endemic Equilibria in England and its Regions. By Rosalyn J. Moran, Alexander J. Billig, Maell Cullen, Adeel Razi, Jean Daunizeau, Rob Leech, Karl J. Friston.

Preprint available on arXiv and software on GitHub.

Dashboard

Regional and local dashboards demonstrating the modelling of COVID-19 using DCM are also available from our website. The data sources are GOV.UK and NHS England.

Software note

The figures in these manuscripts can be reproduced using annotated (MATLAB/Octave) code that is available as part of the free and open source academic software SPM. The routines are called by a demonstration script that can be invoked by typing DEM_COVID , DEM_COVID_X , DEM_COVID_T or DEM_COVID_I at the MATLAB prompt. At the time of writing, these routines are available in the development version of the next SPM release. An archive of the relevant source code for each publication is available from figshare.

The data used in the manuscripts are available from the COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University and Coronavirus (COVID-19) UK Historical Data by Tom White. The CSV files have to be available from the MATLAB path.