Periodic Reporting for period 2 - VEO (Versatile Emerging infectious disease Observatory)
Reporting period: 2021-07-01 to 2022-12-31
The Versatile Emerging infectious disease Observatory (VEO) consortium aims to improve our ability to detect emerging infectious diseases (EIDs) and the spread of antimicrobial resistance (AMR) as early as possible, to enhance Europe’s preparedness to new health threats. VEO aims to do that through an iterative process of data collection and integration between disease experts, data science and technology experts, social scientists, and citizen scientists, seeking to understand disease emergence pathways. That requires combining “traditional” data for disease detection with data that provide information on drivers for emergence. The rationale is that of a One Health lens: humans are part of an ecosystem shared with animals and microbes, and disturbances in these ecosystems and interactions may lead to new disease outbreaks. The VEO platform will support mining, sharing, integration, presentation and analysis of traditional and novel data sources, integrating both publicly available and confidential data.
VEO is being (co)designed and tested through five scenarios, reflecting main pathways of disease emergence, to attune developments to the needs of its intended users, and obtain proof-of-principle of utility, including ethical, legal and social implications. These scenarios represent emergence of a vector-borne (mosquito/tick) disease, a zoonotic disease following spillover from wild life, diseases caused by ecological impact of climate change, and global epidemics from previously localized problems (silent epidemics, for instance AMR). The last scenario is a Disease X scenario, bringing all tools together for a completely unknown emerging disease.
To meet these ambitious goals, VEO has outlined an interconnected workplan, on the one hand developing infrastructure and tools for data mobilization, linking and querying, and on the other hand, bringing together expert teams to work along one of the emergence pathways.
VEO is being (co)designed and tested through five scenarios, reflecting main pathways of disease emergence, to attune developments to the needs of its intended users, and obtain proof-of-principle of utility, including ethical, legal and social implications. These scenarios represent emergence of a vector-borne (mosquito/tick) disease, a zoonotic disease following spillover from wild life, diseases caused by ecological impact of climate change, and global epidemics from previously localized problems (silent epidemics, for instance AMR). The last scenario is a Disease X scenario, bringing all tools together for a completely unknown emerging disease.
To meet these ambitious goals, VEO has outlined an interconnected workplan, on the one hand developing infrastructure and tools for data mobilization, linking and querying, and on the other hand, bringing together expert teams to work along one of the emergence pathways.
VEO participants (and laboratories) were called into action on regional, national and international scales to work on COVID-19. In addition, some of the planned activities were re-focused in order to put scientific expertise within VEO in support of the pandemic response: VEO was involved in development of the first diagnostic PCR and serology assays for COVID-19 in the world; in seminal studies demonstrating the infection kinetics and pathogenesis of COVID-19 in comparison with MERS and SARS in animal models; in studies exploring potential animal reservoirs; in citizen science-based efforts to understand the impact of social media dynamics; in deployment of sewage testing to understand the population-level impact of the pandemic; and in modelling potential trajectories of the pandemic in different scenarios. Upon request by the European commission, VEO helped develop the COVID-19 Data Portal, and built bioinformatic workflows that allow processing of raw sequence data in a standardized manner, complementary to the genome sharing through GISAID. This has provided the largest ever publicly available pathogen genome and variant database open for re-use. The SARS-CoV-2 genomic data constitutes 25% of all globally available genomic data of pathogens, including influenza, polio, measles, foodborne bacteria, TB, and HIV.
Despite the delays due to the pandemic, the use-case scenario workpackages progressed well, with some adjustments to the plans. The mosquito-borne work took the observations of new detections of West Nile Virus (WNV) in Northern Europe. Validated fieldable high-throughput sequencing techniques were used to generate genome datasets used to follow recent WNV outbreaks in Germany, the Netherlands, Italy, Greece and other countries. Based on these data, phylodynamic models were developed to describe the dispersal of WNV lineage II in Europe, and a first exploration was made of factors that contribute to spread.
Along the same lines, VEO partners working on assessing pathways for emergence of zoonotic avian-related viruses focused on the severe outbreaks of highly pathogenic avian influenza viruses (HPAI) in 2021-2022 that were mainly driven by the subtype H5N1 in wild birds along but not limited to the coastal lines of the Baltic and North Sea. We showed that since 2020, the ecology of HPAI H5N1 has made a dramatic shift, also changing the risk of exposure to a wide range of mammals, including humans.
As Greenland is important in the ecology of wild birds and is one of the most affected ecosystems due to climate change, we were interested to study its role in global dissemination of bird-borne and vector-borne pathogens. After postponement of the mission due to SARS-CoV-2 restrictions in 2020 and 2021, a multidisciplinary team was deployed to Greenland in 2022 for trapping, ringing and sampling of potential bird host species. The sampling of wild geese, passerines and waders was successfully conducted and complemented by sample sets including mammalian faecal samples, feathers, sediment and mosquito samples. Analysis of these samples is ongoing, and a second sampling expedition is in preparation.
Part of the silent epidemic scenario is the exploration of the use of wastewater surveillance as an early warning indicator. This approach moved into the spotlight during the pandemic, where wastewater surveillance was established across Europe, including through a Joint Research Centre (JRC) coordinated effort. VEO is exploring how this could be expanded to any pathogen by using metagenomic sequencing, which generates data of a size and complexity that currently is difficult to host in commonly used databases in public health. As a case study, we used metagenomic analysis for antimicrobial resistance of untreated sewage from 101 of the world's 228 countries and their socio-economic, developmental, health and nutritional indicators, as well as collected antimicrobial usage (AMU) data, to characterize and build models predicting the global resistome at the antimicrobial class level. We found that AMU explains only a small proportion of the variation in the global AMR abundance, while the country-specific World Bank's variables explained a large and statistically significant amount.
Despite the delays due to the pandemic, the use-case scenario workpackages progressed well, with some adjustments to the plans. The mosquito-borne work took the observations of new detections of West Nile Virus (WNV) in Northern Europe. Validated fieldable high-throughput sequencing techniques were used to generate genome datasets used to follow recent WNV outbreaks in Germany, the Netherlands, Italy, Greece and other countries. Based on these data, phylodynamic models were developed to describe the dispersal of WNV lineage II in Europe, and a first exploration was made of factors that contribute to spread.
Along the same lines, VEO partners working on assessing pathways for emergence of zoonotic avian-related viruses focused on the severe outbreaks of highly pathogenic avian influenza viruses (HPAI) in 2021-2022 that were mainly driven by the subtype H5N1 in wild birds along but not limited to the coastal lines of the Baltic and North Sea. We showed that since 2020, the ecology of HPAI H5N1 has made a dramatic shift, also changing the risk of exposure to a wide range of mammals, including humans.
As Greenland is important in the ecology of wild birds and is one of the most affected ecosystems due to climate change, we were interested to study its role in global dissemination of bird-borne and vector-borne pathogens. After postponement of the mission due to SARS-CoV-2 restrictions in 2020 and 2021, a multidisciplinary team was deployed to Greenland in 2022 for trapping, ringing and sampling of potential bird host species. The sampling of wild geese, passerines and waders was successfully conducted and complemented by sample sets including mammalian faecal samples, feathers, sediment and mosquito samples. Analysis of these samples is ongoing, and a second sampling expedition is in preparation.
Part of the silent epidemic scenario is the exploration of the use of wastewater surveillance as an early warning indicator. This approach moved into the spotlight during the pandemic, where wastewater surveillance was established across Europe, including through a Joint Research Centre (JRC) coordinated effort. VEO is exploring how this could be expanded to any pathogen by using metagenomic sequencing, which generates data of a size and complexity that currently is difficult to host in commonly used databases in public health. As a case study, we used metagenomic analysis for antimicrobial resistance of untreated sewage from 101 of the world's 228 countries and their socio-economic, developmental, health and nutritional indicators, as well as collected antimicrobial usage (AMU) data, to characterize and build models predicting the global resistome at the antimicrobial class level. We found that AMU explains only a small proportion of the variation in the global AMR abundance, while the country-specific World Bank's variables explained a large and statistically significant amount.
In addition to key contributions to the scientific response to the pandemic, VEO scientists provided the evidence for the trajectory of highly pathogenic avian influenza virus when it expanded globally over the course of the past two years. By similar methods, the expansion of West Nile Virus (WNV) in Europe was studied, showing that the pattern of spread, with repeated new introductions from outside of Europe, as well as lineages established locally, and separate spread pathways from east/central to Southern Europe and northern Europe. Next steps are to define what drives these pathways and what drives the occurrence of outbreaks. The risk targeted sampling, piloted in the mosquito-borne disease emergence scenario, showed that WNV is present in The Netherlands, but there have not been major outbreaks, unlike for Usutu virus, a closely related virus with overlap in mosquito hosts and birds.