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

Background: Following stringent social distancing measures, some European countries are beginning to report a slowed or negative rate of growth of daily case numbers testing positive for the novel coronavirus. The notion that the first wave of infection is close to its peak begs the question of whether future peaks or second waves are likely. We sought to determine the current size of the effective (i.e. susceptible) population for seven European countries - to estimate immunity levels following this first wave. We compare these numbers to the total population sizes of these countries, in order to investigate the potential for future peaks. Methods: We used Bayesian model inversion to estimate epidemic parameters from the reported case and death rates from seven countries using data from late January 2020 to April 5th 2020. Two distinct generative model types were employed: first a continuous time dynamical-systems implementation of a Susceptible-Exposed-Infectious-Recovered (SEIR) model and second: a partially observable Markov Decision Process (MDP) or hidden Markov model (HMM) implementation of an SEIR model. Both models parameterise the size of the initial susceptible population (S0), as well as epidemic parameters. Parameter estimation (data fitting) was performed using a standard Bayesian scheme (variational Laplace) designed to allow for latent unobservable states and uncertainty in model parameters. Results: Both models recapitulated the dynamics of transmissions and disease as given by case and death rates. The peaks of the current waves were predicted to be in the past for four countries (Italy, Spain, Germany and Switzerland) and to emerge in 0.5-2 weeks in Ireland and 1-3 weeks in the UK. For France one model estimated the peak within the past week and the other in the future in two weeks. Crucially, Maximum a posteriori (MAP) estimates of S0 for each country indicated effective population sizes of below 20% (of total population size), under both the continuous time and HMM models. Using for all countries, with a Bayesian weighted average across all seven countries and both models, we estimated that 6.4% of the total population would be immune. From the two models the maximum percentage of the effective population was estimated at 19.6% of the total population for the UK, 16.7% for Ireland, 11.4% for Italy, 12.8% for Spain, 18.8% for France, 4.7% for Germany and 12.9% for Switzerland. Conclusion: Our results indicate that after the current wave, a large proportion of the total population will remain without immunity. This suggests that in the absence of strong seasonal effects, new medications or more comprehensive contact tracing, a further set of epidemic waves in different geographic centres are likely. These findings may have implications for exit strategies from any lockdown stage.

[1]  R. Charrel,et al.  Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[2]  Pejman Rohani,et al.  Appropriate Models for the Management of Infectious Diseases , 2005, PLoS medicine.

[3]  An Pan,et al.  Evolving Epidemiology and Impact of Non-pharmaceutical Interventions on the Outbreak of Coronavirus Disease 2019 in Wuhan, China , 2020, medRxiv.

[4]  G. Leung,et al.  Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study , 2020, The Lancet.

[5]  Carl A. B. Pearson,et al.  The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study , 2020, The Lancet Public Health.

[6]  Adeel Razi,et al.  Dynamic causal modelling of COVID-19 , 2020, Wellcome open research.

[7]  Karl J. Friston,et al.  Variational free energy and the Laplace approximation , 2007, NeuroImage.

[8]  Jeffrey D Sachs,et al.  Projecting hospital utilization during the COVID-19 outbreaks in the United States , 2020, Proceedings of the National Academy of Sciences.

[9]  W. O. Kermack,et al.  A contribution to the mathematical theory of epidemics , 1927 .

[10]  Xinxin Zhang,et al.  Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China , 2020, Cell Discovery.

[11]  Kai Kupferschmidt,et al.  Countries test tactics in 'war' against COVID-19. , 2020, Science.

[12]  Zhilan Feng,et al.  Final and peak epidemic sizes for SEIR models with quarantine and isolation. , 2007, Mathematical biosciences and engineering : MBE.

[13]  G. Sirakoulis,et al.  A cellular automaton model for the effects of population movement and vaccination on epidemic propagation , 2000 .

[14]  C. Viboud,et al.  Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study , 2020, The Lancet Digital Health.

[15]  W. Liang,et al.  Modified SEIR and AI prediction of the epidemics trend of COVID-19 in China under public health interventions , 2020, Journal of thoracic disease.

[16]  D. Shay,et al.  Unraveling R0: considerations for public health applications. , 2014, American journal of public health.

[17]  C. Whittaker,et al.  Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand , 2020 .

[18]  E. Dong,et al.  An interactive web-based dashboard to track COVID-19 in real time , 2020, The Lancet Infectious Diseases.

[19]  Eurosurveillance Editorial Team Updated rapid risk assessment from ECDC on the novel coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[20]  Aravind Srinivasan,et al.  Modelling disease outbreaks in realistic urban social networks , 2004, Nature.

[21]  B. Singer,et al.  Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak , 2020, Proceedings of the National Academy of Sciences.

[22]  N. Linton,et al.  Serial interval of novel coronavirus (COVID-19) infections , 2020, International Journal of Infectious Diseases.

[23]  Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China. , 2020, Cell discovery.

[24]  HighWire Press Proceedings of the Royal Society of London. Series A, Containing papers of a mathematical and physical character , 1934 .