Unravelling Causal Associations between Population Mobility and COVID-19 Cases in Spain: a Transfer Entropy Analysis

Human mobility is a well-known factor in the spread of infectious diseases. During the COVID-19 pandemic, the rapid spread of the SARS-CoV-2 virus led to healthcare systems collapsing in numerous countries, such as Spain and Italy, resulting in a significant number of deaths. To avoid such disastrous outcomes in the future, it is vital to understand how population mobility is linked to the spread of infectious diseases. To assess that, we applied an information theoretic approach called transfer entropy (TE) to measure the influence of the number of infected people travelling between two localities on the future number of infected people in the destination. We first validated our approach using simulated data from a SIR epidemiological model and found that the mobility-based TE was effective in filtering out non-causal influences that could otherwise arise, thereby successfully recovering the epidemic’s spreading patterns and the mobility network topology. We then applied the mobility-based TE to analyse the COVID-19 pandemic in Spain. We identified which regions acted as the main drivers of the pandemic at different periods, both globally and locally. Our results unravelled significant epidemiological events such as the outbreak in Lleida during the Summer of 2020, caused by the influx of temporary workers. We also analysed the effects of a non-pharmaceutical intervention in Catalunya, using mobility- based TE to compare the infection dynamics with a control region. These results help clarify how human mobility influences the dynamic spread of infectious diseases and could be used to inform future non-pharmaceutical interventions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work has received funding from the Horizon 2020 project CREXDATA (ID: 101092749) and UNICO I+D Cloud MePreCisa, funded by MINECO and the EU-Next Generation EU, within the framework of the PRTR and the MRR. CP has received funding from the program "Juan de la Cierva - Formacion" of the Ministry of Education and Science of Spain (ID: FJC2021-046655-I). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes