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WP1: Clinical and genomic epidemiology
In WP1, we combine the nationwide registries in Sweden and Finland (with data from over 17.5 million individuals) for epidemiological studies on NeuroCOVID with an autopsy cohort from the Netherlands and two harmonized clinical cohorts from Italy and Germany to untangle the prevalence, frequency, severity, burden and the duration of neurological sequelae in Post-COVID patients, and to characterize the presence of SARS-CoV-2, neuroinflammation, neurodegeneration, and genetic risk variants in NeuroCOVID as a prerequisite for stratification of NeuroCOVID patients to be analysed in WP2.
The main objectives of WP1 are:
- Evaluate frequency, severity, and course of neurological sequelae in Post-COVID
- Collect biological samples from NeuroCOVID patients and controls
- Detect SARS-CoV-2 neuropathology and genetic risk variants in NeuroCOVID patients’ brains
- Quantify the prevalence and burden of neurological and cognitive-related conditions in COVID-19 patients and offspring of COVID-19 pregnancies from nation-wide data on 17.5 million individuals
- Stratification of NeuroCOVID patients collected for subsequent WPs
WP2: Identification of drivers of cell-intrinsic and cell-nonautonomous neuropathology
WP2 focuses on the integration of immunological phenotyping of selected patients from WP1 and high-throughput neural organoid modelling with the overarching theme to define the cellular and molecular mechanisms for cognitive decline and neurodegenerative processes as the basis for neurological and neuropsychiatric symptoms observed in NeuroCOVID patients. Building on the AI-based analyses proposed in WP3, WP2 will develop a personalised medicine approach to understand cell-type specific CNS vulnerability in NeuroCOVID and determine molecular mechanisms, targets, and biomarkers of cell-autonomous as well as non-autonomous processes of host/pathogen interaction.
The main objectives of WP2 are:
- Identification of personalised NeuroCOVID disease trajectories
- Dissection of cell-intrinsic and cell-nonautonomous neuropathology including the immune response at single-cell resolution following SARS-CoV-2 infection
- Identification of host viral restriction factors in hPSC-derived cortical and dopamine neurons
WP3: Data integration and predictive modelling of CNS vulnerability
WP3 will use the extensive multi-modal data collected to elucidate the molecular underpinnings of NeuroCOVID manifestations, predict which individuals are at higher risk and shed light on the underlying molecular regulatory architecture to inform target identification and drug repurposing. To this end, we will combine clinical data with in vitro data to develop AI-based models of SARS-CoV-2-infected human immune and brain cells, as well as predictive models of vulnerability to SARS-CoV-2 at the individual and population-wide levels.
The main objectives of WP3:
- Define NeuroCOVID multiOMICs profiles at the single-cell and tissue levels
- Assess the value of neural organoids as models of NeuroCOVID
- Functionally map the genome-wide association studies of post-COVID disease
- Learn regulatory networks and links to molecular pathology
- Predict the individual risk of developing NeuroCOVID based on measurable features
WP4: Drug repurposing and personalised pre-clinical trials-in-a-dish
Using information from WP2 and WP3 and linking this patient-derived information with existing knowledge in the field, WP4 will identify drug candidates that might be repositioned to prevent or treat NeuroCOVID symptoms utilizing several complementary computational modelling strategies. Further, promising candidates will be validated using patients’ immune cells and iPSC-derived neurons and region-specific neural organoids (‘personalized pre-clinical trials in a dish’).
The main objectives in WP4 are:
- Computational identification of repositioned drug candidates to prevent/treat NeuroCOVID
- Drug validation in patients’ immune cells and iPSC-derived neurons and region-specific neural organoids
WP5: Social sciences and humanities framework
WP5 is linked to all other WPs as it deals with crucial societal aspects of NeuroCOVID. In particular, it provides qualitative research and analysis of key social aspects related to the lived experiences of NeuroCOVID patients, the emerging forms of social mobilization of COVID-19 patient groups, an analysis of core data ethics and data governance challenges faced in the project and finally policy recommendations to national and EU regulators and policymakers.
The main objectives in WP5 are:
- Qualitative research and analysis of key aspects of societal concern related to the lived experiences of NeuroCOVID patients, and the emerging forms of social mobilization of COVID-19 patient groups
- Analysis of core ELSA challenges faced in the NEUROCOV project
- Policy recommendations to national and EU regulators and policymakers
WP6: Innovation management, ethics, and regulatory affairs
In collaboration with WP5, WP6 will coordinate and monitor the compliance with the legal, ethical, and data protection requirements related to NEUROCOV research activities. WP6 will provide ethical and legal guidance, will liaise with project partners for implementation of necessary compliance measures, and will guarantee that partners' ethics committees and legal departments can rely on a project-internal, specialized contact point.
Following a multidimensional, integrated and impact-oriented approach, WP6 provides innovation management for the project. It will ensure consistent communication, effective dissemination, and strategic results exploitation. A proper Intellectual Property (IP) management strategy will lay the foundation for further exploitation activities.
The main objectives of WP6 are:
- Communication, creating visibility and encouraging project outreach
- Disseminating results to targeted stakeholders and the scientific community
- Fostering innovation capacity and exploitation of results – including IP management
- Ethics compliance
- Harmonized data governance framework
WP7: Project management, scientific coordination, and data management
WP7 will provide a clear organisational framework, guidance, and all support mechanisms to enable a smooth project workflow in NEUROCOV and to ensure that objectives and milestones will be met on time.
The main objectives of WP7 are:
- Quick set-up of management & communication structures and processes
- Central monitoring of project activities, deliverables, and deadlines.
- Ensure efficiency, high quality, and maximum usability of project outcomes.
- Proper risk analysis and conflict management.