For the first time in history, on March 17, 2020, the European Union closed all its external borders in an attempt to contain the spreading of the coronavirus 2019, COVID-19. Throughout two past months, governments around the world have implemented massive travel restrictions and border control to mitigate the outbreak of this global pandemic. However, the precise effects of travel restrictions on the outbreak dynamics of COVID-19 remain unknown. Here we combine a global network mobility model with a local epidemiology model to simulate and predict the outbreak dynamics and outbreak control of COVID-19 across Europe. We correlate our mobility model to passenger air travel statistics and calibrate our epidemiology model using the number of reported COVID-19 cases for each country. Our simulations show that mobility networks of air travel can predict the emerging global diffusion pattern of a pandemic at the early stages of the outbreak. Our results suggest that an unconstrained mobility would have significantly accelerated the spreading of COVID-19, especially in Central Europe, Spain, and France. Ultimately, our network epidemiology model can inform political decision making and help identify exit strategies from current travel restrictions and total lockdown. ARTICLE HISTORY

For the first time in history, on March 17,2020, the European Union closed all its external borders to contain the spreading of the coronavirus 2019, COVID-19. Throughout two past months, governments around the world have implemented massive travel restrictions and border control to mitigate the outbreak of this global pandemic. However, the precise effects of travel restrictions on the outbreak dynamics of COVID-19 remain unknown. Here we combine a global network mobility model with a local epidemiology model to simulate and predict the outbreak dynamics and outbreak control of COVID-19 across Europe. We correlate our mobility model to passenger air travel statistics and calibrate our epidemiology model using the number of reported COVID-19 cases for each country. Our simulations show that mobility networks of air travel can predict the emerging global diffusion pattern of a pandemic at the early stages of the outbreak. Our results suggest that an unconstrained mobility would have significantly accelerated the spreading of COVID-19, especially in Central Europe, Spain, and France. Ultimately, our network epidemiology model can inform political decision making and help identify exit strategies from current travel restrictions and total lockdown.

Throughout the past six months, no number has dominated the public media more persistently than the reproduction number of COVID-19. This powerful but simple concept is widely used by the public media, scientists, and political decision makers to explain and justify political strategies to control the COVID-19 pandemic. Here we explore the effectiveness of political interventions using the reproduction number of COVID-19 across Europe. We propose a dynamic SEIR epidemiology model with a time-varying reproduction number, which we identify using machine learning. During the early outbreak, the basic reproduction number was 4.22 ± 1.69, with maximum values of 6.33 and 5.88 in Germany and the Netherlands. By May 10, 2020, it dropped to 0.67 ± 0.18, with minimum values of 0.37 and 0.28 in Hungary and Slovakia. We found a strong correlation between passenger air travel, driving, walking, and transit mobility and the effective reproduction number with a time delay of 17.24 ± 2.00 days. Our new dynamic SEIR model provides the flexibility to simulate various outbreak control and exit strategies to inform political decision making and identify safe solutions in the benefit of global health.

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in n = 30 provinces, we found a latent period of 2.56 ± 0.72 days, a contact period of 1.47 ± 0.32 days, and an infectious period of 17.82 ± 2.95 days. We postulate that the latent and infectious periods are disease-specific, whereas the contact period is behavior-specific and can vary between different provinces, states, or countries. For the early stages of the outbreak in the United States, in n = 50 states, we adopted the disease-specific values from China and found a contact period of 3.38 ± 0.69 days. Our network model predicts that-without the massive political mitigation strategies that are in place todaythe United States would have faced a basic reproduction number of 5.30 ± 0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lockdown, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in n = 30 provinces, we found a latent period of 2.56±0.72 days, a contact period of 1.47±0.32 days, and an infectious period of 17.82±2.95 days. We postulate that the latent and infectious periods are disease-specific, whereas the contact period is behavior-specific and can vary between different provinces, states, or countries. For the early stages of the outbreak in the United States, in n = 50 states, we adopted the disease-specific values from China, and found a contact period of 3.38±0.69 days. Our network model predicts that-without the massive political mitigation strategies that are in place today-the United states would have faced a basic reproduction number of 5.3±0.95 and a nationwide peak of the outbreak

Throughout the past four months, no number has dominated the public media more persistently than the reproduction number of COVID-19. This powerful but simple concept is widely used by the public media, scientists, and political decision makers to explain and justify political strategies to control the COVID-19 pandemic. Here we explore the effectiveness of political interventions using the reproduction number of COVID-19 across Europe. We propose a dynamic SEIR epidemiology model with a time-varying reproduction number, which we identify using machine learning and uncertainty quantification. During the early outbreak, the reproduction number was 4.5±21.4, with maximum values of 6.5 and 5.9 in Spain and France. As of today, it has dropped to 0.7±20.2, with minimum values of 0.4 and 0.3 in Austria and France. We found a strong correlation between passenger air travel and the reproduction number with a time delay of 12.6±22.7 days. Our new dynamic SEIR model provides the flexibility to simulate various outbreak control and exit strategies to inform political decision making and identify safe solutions in the benefit of global health.

Cardiovascular disease in women remains under-diagnosed and under-treated. Recent studies suggest that this is caused, at least in part, by the lack of sex-specific diagnostic criteria. While it is widely recognized that the female heart is smaller than the male heart, it has long been ignored that it also has a different microstructural architecture. This has severe implications on a multitude of cardiac parameters. Here, we systematically review and compare geometric, functional, and structural parameters of female and male hearts, both in the healthy population and in athletes. Our study finds that, compared to the male heart, the female heart has a larger ejection fraction and beats at a faster rate but generates a smaller cardiac output. It has a lower blood pressure but produces universally larger contractile strains. Critically, allometric scaling, e.g., by lean body mass, reduces but does not completely eliminate the sex differences between female and male hearts. Our results suggest that the sex differences in cardiac form and function are too complex to be ignored: the female heart is not just a small version of the male heart. When using similar diagnostic criteria for female and male hearts, cardiac disease in women is frequently overlooked by routine exams, and it is diagnosed later and with more severe symptoms than in men. Clearly, there is an urgent need to better understand the female heart and design sex-specific diagnostic criteria that will allow us to diagnose cardiac disease in women equally as early, robustly, and reliably as in men.Systematic Review Registrationhttps://livingmatter.stanford.edu/.

Understanding the outbreak dynamics of the COVID-19 pandemic has important implications for successful containment and mitigation strategies. Recent studies suggest that the population prevalence of SARS-CoV-2 antibodies, a proxy for the number of asymptomatic cases, could be an order of magnitude larger than expected from the number of reported symptomatic cases. Knowing the precise prevalence and contagiousness of asymptomatic transmission is critical to estimate the overall dimension and pandemic potential of COVID-19. However, at this stage, the effect of the asymptomatic population, its size, and its outbreak dynamics remain largely unknown. Here we use reported symptomatic case data in conjunction with antibody seroprevalence studies, a mathematical epidemiology model, and a Bayesian framework to infer the epidemiological characteristics of COVID-19. Our model computes, in real time, the time-varying contact rate of the outbreak, and projects the temporal evolution and credible intervals of the effective reproduction number and the symptomatic, asymptomatic, and recovered populations. Our study quantifies the sensitivity of the outbreak dynamics of COVID-19 to three parameters: the effective reproduction number, the ratio between the symptomatic and asymptomatic populations, and the infectious periods of both groups For nine distinct locations, our model estimates the fraction of the population that has been infected and recovered by Jun 15, 2020 to 24.15% (95% CI: 20.48%-28.14%) for Heinsberg (NRW, Germany), 2.40% (95% CI: 2.09%-2.76%) for Ada County (ID, USA), 46.19% (95% CI: 45.81%-46.60%) for New York City (NY, USA), 11.26% (95% CI: 7.21%-16.03%) for Santa Clara County (CA, USA), 3.09% (95% CI: 2.27%-4.03%) for Denmark, 12.35% (95% CI: 10.03%-15.18%) for Geneva Canton (Switzerland), 5.24% (95% CI: 4.84%-5.70%) for the Netherlands, 1.53% (95% CI: 0.76%-2.62%) for Rio Grande do Sul (Brazil), and 5.32% (95% CI: 4.77%-5.93%) for Belgium. Our method traces the initial outbreak date in Santa Clara County back to January 20, 2020 (95% CI: December 29, 2019 - February 13, 2020). Our results could significantly change our understanding and management of the COVID-19 pandemic: A large asymptomatic population will make isolation, containment, and tracing of individual cases challenging. Instead, managing community transmission through increasing population awareness, promoting physical distancing, and encouraging behavioral changes could become more relevant.