Background

Although it was initially detected through its impact on the respiratory system, COVID-19 is now recognized as a multisystemic disease, and the nervous system is one of its main targets. SARS-CoV-2 infects host cells through the binding of its spike protein to a surface receptor known as angiotensin-converting enzyme 2 (ACE2), which is widely expressed in the CNS.Structural similarities found between SARS-CoV-2 and other coronaviruses have indicated early on that it might have neuroinvasive and neurotropic potential, with studies of coronaviruses involved in previous outbreaks showing serious CNS complications. Links between coronavirus infections and neurodegenerative diseases have also been proposed in the past, as antigens and RNA from CoVs have been detected in the brain and CSF of patients with multiple sclerosis and Parkinsons disease.

Now, as the COVID-19 pandemic enters its second year, the neurological impact of SARS-CoV2 infection is becoming increasingly apparent. In addition, long-term consequences of infection are being investigated as recovering patients report fatigue and brain fogginess. A few follow-up studies have indicated neuropsychiatric alterations, as well as endocrine, hematologic, and gastrointestinal symptoms afflicting COVID long-haulers. It is crucial to investigate in detail the long-term effects of SARS-CoV2 infection, as neurological outcomes in COVID-19 long-haulers may become a prominent concern for health care systems in the coming years.

Quantitative assessment of video-based eye tracking has become a very attractive means to assess brain function and dysfunction because: 1) the method is simple and non-invasive, subjects look at a computer screen while a remote camera records the eye; and 2) knowledge of cortical and subcortical brain circuits is extensive so that deficits can be mapped to specific brain circuits. These include regions of the visual system, parietal and frontal cortex, basal ganglia, thalamus, superior colliculus, cerebellum, and brainstem. There is often overlap with pathophysiology in many neurological and psychiatric disorders. Therefore, the eye movement system can be used as an effective tool to probe sensory, motor, and cognitive function to search for specific biomarkers of brain disease.

Technology Overview

At the beginning of the COVID-19 pandemic, Queen’s researchers predicted that there would be neurological consequences of infection. They established a research network involving Queen’s University and the D’Or Institute for Research and Education (IDOR) in Brazil. The researchers took advantage of this unique opportunity to send an eye tracker and a trainee to Brazil to begin collecting eye tracking data in COVID-19 recovering patients so that they could quantify sensory, motor, cognitive, and autonomic functions. This effort is already providing new and valuable preliminary data, shown in this proposal, on the long-term consequences of COVID-19 on cognitive and brain function. In a similar way, the researchers are taking advantage of this ongoing collaboration with researchers in Mexico, where the researchers have previously tested patients with neurodegenerative diseases, to collect data from a cohort of recovering COVID-19 patients that is now being followed at the Universidad Nacional Autónoma de México and the INCMNSZ. This proposal is focused on collecting and analyzing the eye tracking data and then on correlating the eye tracking data with clinical, cognitive, molecular and brain imaging data.

The researchers started collecting COVID-19 eye-tracking data in Rio de Janeiro in January, 2021. To date they have recorded 23 COVID-19 patients. The collected data has been compared to 35 age-matched control participants recruited from the MUNOZ lab database. These control experiments were conducted in Kingston, Canada using identical equipment. The database includes 535 controls (ages 2-95), as well as patients diagnosed with Parkinson’s disease, Alzheimer’s disease, mild cognitive impairment, Huntington’s disease, REM sleep behaviour disorder, progressive supranuclear palsy, multisystem atrophy, amyotrophic lateral sclerosis, cerebrovascular disease, bipolar disorder, attention deficit hyperactivity disorder, depression, and fetal alcohol spectrum disorder. The researcher’s analysis revealed that sensory and motor pathways are intact and functioning normally in COVID-19 as indicated by pro-saccade measures. In sharp contrast, anti-saccade behaviour was significantly impaired in the COVID-19 patients which is characteristic of cognitive impairment.

AIM 1. Use video-based eye tracking to identify cognitive abnormalities. Patients and controls will perform structured and unstructured visual oculomotor tasks designed to probe top-down and bottom-up control of gaze and quantify deficits in sensory, motor, autonomic, and cognitive control that impact aspects of saccade, pupil, and blink behaviour the researchers have discovered in this research (an recently filed a patent application on - May 2021). These variables will be compared to age-matched controls as well as other data sets collected from neurological patients.

AIM 2. Correlate eye tracking variables with clinical, cognitive, molecular, and imaging biomarkers. The same participants recruited to Aim 1 will also be assessed with clinical, cognitive, molecular, and imaging protocols. The researchers can leverage this opportunity to correlate eye tracking variables with these clinical, cognitive, molecular, and imaging data sets.

Aim 2a) Correlate eye tracking variables with clinical data and cognitive test batteries

Aim 2b) Correlate eye tracking variables with molecular (CSF, blood) biomarkers.

Aim 2c) Correlate eye tracking variables with structural and functional neuroimaging

Stage of Development

Started collecting eye tracking data in Rio de Janeiro in January, 2021. To date the researchers have recorded 23 COVID-19 patients.

Benefits

There is now widespread evidence of long-term CNS abnormalities associated with COVID-19 infection. This will likely develop into a huge emerging problem for world health care systems as a tsunami of patients will likely emerge with clinical and subclinical CNS abnormalities. However, there are no simple assessment tools that can quickly and quantitatively assess brain circuits and function to determine underlying CNS problems.

Results from this proposal are expected to establish eye-tracking as a non-invasive tool capable of identifying COVID-19 patients at risk for neurological impairments and tracking them longitudinally. The researchers will be in an unique position to apply this knowledge to evaluate and track in detail the long-term consequences of COVID-19 on cognitive and brain function.

Applications

Detection of COVID-19 induced neurological damage
Longitudinal tracking of neurological damage in COVID-19 patients
Follow treatment efficacy in affected patients

Opportunity

The researchers are currently in the process of creating a NewCo to commercialize their eye-tracking algorithms for diagnosing neurodegenerative and psychiatric diseases. To that end they would welcome discussions on investment into supporting the company. However, they would also be open to discussions on research funding supporting identification and validation of eye-tracking classifiers for COVID-specific neurological damage.

Diagnosing Cognitive Impairment After COVID-19 Infection

Patents

IP Status

Seeking