KEY RESEARCH LINES OF INQUIRY

A Framework for Progress

Drawing from a comprehensive literature review and input from our Science Advisory Council – composed of leading Canadian researchers and clinician scientists in virology, immunology and neurology – we have summarized the key lines of inquiry for understanding how viruses such as SARS-CoV-2 can affect the central nervous system (CNS).

Progress will rely on a strong basic research foundation into (i) which cell types can be infected by SARS-CoV-2, (ii) what conditions allow viruses to invade the central nervous system and (iii) how best to diagnose and treat long-term neurological consequences of COVID-infection. Accordingly, the following research topics are situated along the translational medical research continuum to create a robust approach to understanding viral neuroinvasion – from lab-bench to population health.

1.0 Risk-factors for neuro-COVID

1.1 Obtain data (clinical, behaviour, biospecimen, genetic, imaging) in patients

1.2 Identify association between each measure and neuro-COVID

2.0 Neuropathogenesis – origination and development – of neuro-COVID

2.1 Confirm that SARS-CoV-2 has the ability to invade the CNS, i.e. is neuroinvasive, through the collection of cerebrospinal fluid (CSF) and other CNS tissue samples.

2.2 Understand mechanism of neuroinvasion: How does the virus enter the CNS and propagate?

2.2.1 Viral tropism: Which types of cells and tissues does the virus infect? Does SARS-CoV-2 attack the CNS preferentially, i.e. is the virus neurotropic?

2.2.2 Evidence for various pathways of entry and propagation. May include animal models.;

3.0 Diagnostic potential

3.1 Identify and measure molecular biomarkers of CNS infection and/or inflammation

3.2 Understand and classify clinical manifestations of neuro-COVID in patients

4.0 Long-term sequelae and elucidating linkages to neurological disease

4.1 Measure and categorize cognitive and neurological deficits.

4.2 Relate neurological sequalae to primary symptomology of SARS-CoV-2.

5.0 Potential therapeutics

5.1 Mitigate risk-factors

5.2 Prevent viral neuroinvasion

5.3 Treat associated and ongoing neurodegenerative disease

Across all: sex and gender considerations; ethical, social and legal implications, where relevant