Dynamic causal modeling of the COVID-19 pandemic in northern Italy predicts possible scenarios for the second wave

The COVID-19 pandemic has sparked an intense debate about the factors underlying the dynamics of the outbreak. Mitigating virus spread could benefit from reliable predictive models that inform effective social and healthcare strategies. Crucially, the predictive validity of these models depends upon incorporating behavioral and social responses to infection that underwrite ongoing social and healthcare strategies. Formally, the problem at hand is not unlike the one faced in neuroscience when modelling brain dynamics in terms of the activity of a neural network: the recent COVID19 pandemic develops in epicenters (e.g. cities or regions) and diffuses through transmission channels (e.g., population fluxes). Indeed, the analytic framework known as "Dynamic Causal Modeling" (DCM) has recently been applied to the COVID-19 pandemic, shedding new light on the mechanisms and latent factors driving its evolution. The DCM approach rests on a time-series generative model that provides - through Bayesian model inversion and inference - estimates of the factors underlying the progression of the pandemic. We have applied DCM to data from northern Italian regions, which were the first areas in Europe to contend with the COVID-19 outbreak. We used official data on the number of daily confirmed cases, recovered cases, deaths and performed tests. The model - parameterized using data from the first months of the pandemic phase - was able to accurately predict its subsequent evolution (including social mobility, as assessed through GPS monitoring, and seroprevalence, as assessed through serologic testing) and revealed the potential factors underlying regional heterogeneity. Importantly, the model predicts that a second wave could arise due to a loss of effective immunity after about 7 months. This second wave was predicted to be substantially worse if outbreaks are not promptly isolated and contained. In short, dynamic causal modelling appears to be a reliable tool to shape and predict the spread of the COVID-19, and to identify the containment and control strategies that could efficiently counteract its second wave, until effective vaccines become available.

[1]  Henrique Mohallem Paiva,et al.  A data-driven model to describe and forecast the dynamics of COVID-19 transmission , 2020, PloS one.

[2]  A. L. Schmidt,et al.  Economic and social consequences of human mobility restrictions under COVID-19 , 2020, Proceedings of the National Academy of Sciences.

[3]  Adeel Razi,et al.  Testing and tracking in the UK: A dynamic causal modelling study , 2020, Wellcome Open Research.

[4]  Supinda Bunyavanich,et al.  Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults. , 2020, JAMA.

[5]  V. Colizza,et al.  Impact of lockdown on COVID-19 epidemic in Île-de-France and possible exit strategies , 2020, BMC Medicine.

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

[7]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[8]  J. Greenbaum,et al.  Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals , 2020, Cell.

[9]  A. Vespignani,et al.  Modelling the impact of testing, contact tracing and household quarantine on second waves of COVID-19 , 2020, Nature Human Behaviour.

[10]  Hannah R. Meredith,et al.  The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application , 2020, Annals of Internal Medicine.

[11]  N. Low,et al.  Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: A modeling study in Hubei, China, and six regions in Europe , 2020, PLoS medicine.

[12]  Christopher Earl,et al.  Preexisting and de novo humoral immunity to SARS-CoV-2 in humans , 2020, Science.

[13]  Jim Koopman,et al.  Modeling infection transmission. , 2004, Annual review of public health.

[14]  K. Rothman,et al.  Satellite-detected tropospheric nitrogen dioxide and spread of SARS-CoV-2 infection in Northern Italy , 2020, Science of The Total Environment.

[15]  Sang Woo Park,et al.  Mathematical models to guide pandemic response , 2020, Science.

[16]  R. Geskus,et al.  The natural history and transmission potential of asymptomatic SARS-CoV-2 infection , 2020, medRxiv.

[17]  Joel Hellewell,et al.  Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study , 2020, The Lancet Infectious Diseases.

[18]  Adeel Razi,et al.  Effective immunity and second waves: a dynamic causal modelling study. , 2020, Wellcome open research.

[19]  M. Jit,et al.  Modelling the transmission of healthcare associated infections: a systematic review , 2013, BMC Infectious Diseases.

[20]  Adeel Razi,et al.  Second waves, social distancing, and the spread of COVID-19 across the USA , 2020, Wellcome open research.

[21]  Ruiyun Li,et al.  Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2) , 2020, Science.

[22]  Guido Gnone,et al.  The COVID-19 infection: lessons from the Italian experience , 2020, Journal of public health policy.

[23]  Giuliano Rizzardini,et al.  Genomic characterization and phylogenetic analysis of SARS‐COV‐2 in Italy , 2020, Journal of medical virology.

[24]  Zhigang Tian,et al.  Functional exhaustion of antiviral lymphocytes in COVID-19 patients , 2020, Cellular & Molecular Immunology.

[25]  Nuno R. Faria,et al.  The effect of human mobility and control measures on the COVID-19 epidemic in China , 2020, Science.

[26]  M. Lipsitch,et al.  Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period , 2020, Science.

[27]  Modeling the Novel Coronavirus (SARS-CoV-2) Outbreak in Sicily, Italy , 2020, International journal of environmental research and public health.

[28]  P. Koumoutsakos,et al.  Data-driven inference of the reproduction number for COVID-19 before and after interventions for 51 European countries. , 2020, Swiss medical weekly.

[29]  K. Rothman,et al.  Lockdown timing and efficacy in controlling COVID-19 using mobile phone tracking , 2020, EClinicalMedicine.

[30]  Luis Unigarro,et al.  Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review , 2020, Diagnostic Microbiology and Infectious Disease.

[31]  Salvatore Ercolano,et al.  The Efficacy of Lockdown Against COVID-19: A Cross-Country Panel Analysis , 2020, Applied Health Economics and Health Policy.

[32]  S. Salmaso,et al.  Protecting our health care workers while protecting our communities during the COVID-19 pandemic: a comparison of approaches and early outcomes in two Italian regions, Italy, 2020 , 2020, medRxiv.

[33]  Aurelio Tobías,et al.  Evaluation of the lockdowns for the SARS-CoV-2 epidemic in Italy and Spain after one month follow up , 2020, Science of The Total Environment.

[34]  Jessica T Davis,et al.  The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak , 2020, Science.

[35]  A. L. Schmidt,et al.  Economic and social consequences of human mobility restrictions under COVID-19 , 2020, Proceedings of the National Academy of Sciences.

[36]  L. Amato,et al.  Volume and health outcomes: evidence from systematic reviews and from evaluation of Italian hospital data. , 2017, Epidemiologia e prevenzione.

[37]  Karl J. Friston,et al.  Effective immunity and second waves: a dynamic causal modelling study , 2020, Wellcome open research.