Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave.

Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally1-7. Although a limited number of SARS-CoV-2 introductions were reported in January and February 2020 (refs.8,9), the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening10, left many countries vulnerable to unmitigated, cryptic transmission. Here we use a global metapopulation epidemic model to provide a mechanistic understanding of the early dispersal of infections and the temporal windows of the introduction of SARS-CoV-2 and onset of local transmission in Europe and the USA. We find that community transmission of SARS-CoV-2 was likely to have been present in several areas of Europe and the USA by January 2020, and estimate that by early March, only 1 to 4 in 100 SARS-CoV-2 infections were detected by surveillance systems. The modelling results highlight international travel as the key driver of the introduction of SARS-CoV-2, with possible introductions and transmission events as early as December 2019 to January 2020. We find a heterogeneous geographic distribution of cumulative infection attack rates by 4 July 2020, ranging from 0.78% to 15.2% across US states and 0.19% to 13.2% in European countries. Our approach complements phylogenetic analyses and other surveillance approaches and provides insights that can be used to design innovative, model-driven surveillance systems that guide enhanced testing and response strategies.

The GLEaMviz computational tool, a publicly available software to explore realistic epidemic spreading scenarios at the global scale.

BACKGROUND: Computational models play an increasingly important role in the assessment and control of public health crises, as demonstrated during the 2009 H1N1 influenza pandemic. Much research has been done in recent years in the development of sophisticated data-driven models for realistic computer-based simulations of infectious disease spreading. However, only a few computational tools are presently available for assessing scenarios, predicting epidemic evolutions, and managing health emergencies that can benefit a broad audience of users including policy makers and health institutions. RESULTS: We present "GLEaMviz", a publicly available software system that simulates the spread of emerging human-to-human infectious diseases across the world. The GLEaMviz tool comprises three components: the client application, the proxy middleware, and the simulation engine. The latter two components constitute the GLEaMviz server. The simulation engine leverages on the Global Epidemic and Mobility (GLEaM) framework, a stochastic computational scheme that integrates worldwide high-resolution demographic and mobility data to simulate disease spread on the global scale. The GLEaMviz design aims at maximizing flexibility in defining the disease compartmental model and configuring the simulation scenario; it allows the user to set a variety of parameters including: compartment-specific features, transition values, and environmental effects. The output is a dynamic map and a corresponding set of charts that quantitatively describe the geo-temporal evolution of the disease. The software is designed as a client-server system. The multi-platform client, which can be installed on the user's local machine, is used to set up simulations that will be executed on the server, thus avoiding specific requirements for large computational capabilities on the user side. CONCLUSIONS: The user-friendly graphical interface of the GLEaMviz tool, along with its high level of detail and the realism of its embedded modeling approach, opens up the platform to simulate realistic epidemic scenarios. These features make the GLEaMviz computational tool a convenient teaching/training tool as well as a first step toward the development of a computational tool aimed at facilitating the use and exploitation of computational models for the policy making and scenario analysis of infectious disease outbreaks.

Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave in Europe and the United States.

Given the narrowness of the initial testing criteria, the SARS-CoV-2 virus spread through cryptic transmission in January and February, setting the stage for the epidemic wave experienced in March and April, 2020. We use a global metapopulation epidemic model to provide a mechanistic understanding of the global dynamic underlying the establishment of the COVID-19 pandemic in Europe and the United States (US). The model is calibrated on international case introductions at the early stage of the pandemic. We find that widespread community transmission of SARS-CoV-2 was likely in several areas of Europe and the US by January 2020, and estimate that by early March, only 1 - 3 in 100 SARS-CoV-2 infections were detected by surveillance systems. Modeling results indicate international travel as the key driver of the introduction of SARS-CoV-2 with possible importation and transmission events as early as December, 2019. We characterize the resulting heterogeneous spatio-temporal spread of SARS-CoV-2 and the burden of the first COVID-19 wave (February-July 2020). We estimate infection attack rates ranging from 0.78%-15.2% in the US and 0.19%-13.2% in Europe. The spatial modeling of SARS-CoV-2 introductions and spreading provides insights into the design of innovative, model-driven surveillance systems and preparedness plans that have a broader initial capacity and indication for testing.

Estimating the establishment of local transmission and the cryptic phase of the COVID-19 pandemic in the USA.

We use a global metapopulation transmission model to study the establishment of sustained and undetected community transmission of the COVID-19 pandemic in the United States. The model is calibrated on international case importations from mainland China and takes into account travel restrictions to and from international destinations. We estimate widespread community transmission of SARS-CoV-2 in February, 2020. Modeling results indicate international travel as the key driver of the introduction of SARS-CoV-2 in the West and East Coast metropolitan areas that could have been seeded as early as late-December, 2019. For most of the continental states the largest contribution of imported infections arrived through domestic travel flows.

The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak.

Motivated by the rapid spread of coronavirus disease 2019 (COVID-19) in mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated on the basis of internationally reported cases and shows that, at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in mainland China but had a more marked effect on the international scale, where case importations were reduced by nearly 80% until mid-February. Modeling results also indicate that sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.

The effect of travel restrictions on the spread of the 2019 novel coronavirus (2019-nCoV) outbreak.

Motivated by the rapid spread of a novel coronavirus (2019-nCoV) in Mainland China, we use a global metapopulation disease transmission model to project the impact of both domestic and international travel limitations on the national and international spread of the epidemic. The model is calibrated on the evidence of internationally imported cases before the implementation of the travel quarantine of Wuhan. By assuming a generation time of 7.5 days, the reproduction number is estimated to be 2.4 [90% CI 2.2-2.6]. The median estimate for number of cases before the travel ban implementation on January 23, 2020 is 58,956 [90% CI 40,759 - 87,471] in Wuhan and 3,491 [90% CI 1,924 - 7,360] in other locations in Mainland China. The model shows that as of January 23, most Chinese cities had already received a considerable number of infected cases, and the travel quarantine delays the overall epidemic progression by only 3 to 5 days. The travel quarantine has a more marked effect at the international scale, where we estimate the number of case importations to be reduced by 80% until the end of February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.