NeuroCOV's impact on scientific research is far-reaching and multi-tiered.
The project will uncover the risk factors underlying the cognitive and neurodegenerative manifestations of post-COVID across a thorough range of variables: host genetic make-up, comorbidities, socioeconomic status, immune status (acquired either through vaccination or prior infection), course of acute COVID-19 and single-cell resolved high-resolution molecular profiles of pathophysiologically relevant blood and CNS samples. NeuroCOV will thereby provide healthcare stakeholders with enhanced knowledge of NeuroCOVID. Long-term beneficial effects of such expanded knowledge will include an advanced ability to respond to and manage the looming health emergency.
The establishment of patient-specific models for neural-specific host-virus interplay and the definition of a wide range of individual NeuroCOVID disease trajectories will provide robust evidence to guide decision-making for personalised therapeutic interventions. Through targeted dissemination for early industrial uptake and clinical translation, this outcome is poised to have a significant, long-term impact towards reducing the health burden of NeuroCOVID. In addition, such translational pipelines are expected to act as proof of principle templates in tackling other neuroimmunological conditions.
To define criteria for the personalised risk assessment of developing NeuroCOVID complications, NeuroCOV will develop Artificial Intelligence (AI)-based predictive models. These models will allow assessment of likely trajectory/severity and will build the basis to provide biomarkers and signatures for the assessment of NeuroCOVID status and risk.
In order to study host-virus interactions and the chronic pro-inflammatory changes following viral infection in the CNS, NeuroCOV will develop highly defined and multimodular hPSC-based disease models. This will enable neuroimmunologists to study existing neurotropic viruses and new viral pathogens that may cause CNS complications during future pandemics.
The application of the developed multimodular and scalable hPSC-disease models will result in increased knowledge of the cell-intrinsic and cell-nonautonomous disease mechanisms of SARS-CoV-2 in the CNS. Additionally, it will lead to the screening of potential therapeutic targets and repurposed drugs for NeuroCOVID.
Considering the genetic diversity within the population and the heterogeneity of clinical symptoms, these models must be scalable and patient-specific, allowing for the dissection of personalised disease trajectories.
For the identification of therapeutic avenues to tackle NeuroCOVID, NeuroCOV has designed complementary approaches to focus on the identification of drug repositioning opportunities, which offer multiple advantages over developing new compounds from scratch: from the established safety profiles of repurposable drugs to their path to re-approval and the ensuing speed and cost-effectiveness of clinical translation.
The major aim is to elucidate factors critical for preventing SARS-CoV-2 directly or indirectly mediated damage (through the immune/inflammatory reaction) to the CNS.
The molecular knowledge generated in the project will be complemented with increased awareness of key social challenges faced by NeuroCOVID patient populations. Interview data with COVID-19 disease advocacy groups will enable the probing of emerging forms of patient advocacy mobilisation towards the definition of new disease categories, reimbursement, and social policy on the national and European levels.
As a result, we expect the following wider impact: policymakers will be better prepared to respond effectively to the social (on top of the medical) predicaments faced by NeuroCOVID, and be able to devise effective social policies accordingly. Knowledge of the broader, not strictly medical, predicaments of NeuroCOVID creates higher sensitivity towards the social factors that may detract from the well-being of this social group, thus strengthening the pandemic preparedness capacity of our societies.