Exploring Brain Damages After COVID-19 Infection

Study Overview
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Brief Summary
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Although direct evidence is currently lacking, the high identity between SARS-CoV-1 and SARS-CoV-2 suggests, that the latter viral strain could also infect the Central Nervous System (CNS). Indeed, some cases of SARS-COV2 encephalitis begin to be described and CNS damages are increasingly highlighted in the literature, but still not objectified by imaging and do not allow to explain the entire clinical patterns. We hypothesise that these CNS damages are not always objectified by Magnetic Resonance Imaging (MRI) but could be indirectly observed by a physiological dysfunction of neural conduction in the brainstem. We will explore brainstem disruption through an electrophysiological approach.

Detailed Description
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Clinical and preclinical data from studies with other coronaviruses suggest an evident neurotropism, which may result in more complex clinical scenarios. Can the SARS-CoV-2 enter the Central Nervous System (CNS) and infect neural cells ? And if yes, how the CNS damage contributes to pathophysiology of the COVID-19, to its signs, symptoms and progression as well as to its sequelae. It has been demonstrated that coronaviruses such as SARS-CoV and MERS-CoV do not limit their presence to the respiratory tract and frequently invade the CNS. The intranasal administration of SARS-CoV-1 or MERS-COV resulted in the rapid invasion of viral particles into the brain of mice, possibly through the olfactory bulb via trans-synaptic route. The brainstem, which hosts the respiratory neuronal circuit in the medulla, was severely infected with both types of viruses, which may contribute to degradation and failure of respiratory centres.

Official Title
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Exploring Brain Damages After COVID-19 Infection

Conditions
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SARS-CoV 2

Intervention / Treatment
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* Procedure: Auditory Evoked Potentials (AEP)
* Procedure: Blink and Masseter Inhibitory Reflex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Age ≥ 18 years. Hospitalized patient suffering from a positive COVID 19 diagnosed by Reverse transcription polymerase chain reaction (RT-PCR) or chest computed tomography scan (CTscan) with specific lesions Exclusion Criteria : History of neurological damage interfering with auditory evoked potentials (PEA) and Electromyography (EMG) reflexes of the brainstem (stroke of the brainstem, acoustic neuroma, amyotrophic lateral sclerosis, facial diplegia, damage to nerves V or VII, etc.) Impaired alertness Sedative treatments or treatments that disturb nerve conduction. Pregnancy or breastfeeding Individuals under legal protection or unable to express personally their consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electrophysiological procedure<br>Brainstem reflexes and neural conduction will be explored using Auditory Evoked Potentials (AEP) and blink and Masseter Inhibitory Reflex (MIR) in hospitalised patients with COVID infection | Procedure: Auditory Evoked Potentials (AEP)<br>* Record of electrophysiological responses (Auditory Evoked Potentials or AEP) during auditory stimulations with an electroencephalogram (EEG).<br>Procedure: Blink and Masseter Inhibitory Reflex<br>* Electrophysiological exploration while stimulating trigeminal nerve to record 1) motor response induced (muscle contraction delay (Blink)) of the facial nerve, or 2) the contraction inhibition of masseters (Masseter Inhibitory Reflex (MIR)).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Latency of electrophysiological response | Latencies of electrophysiological responses with Auditory Evoked Potentials | Inclusion (T0) | 
| Delay of Muscle contraction | Delay of Muscle contraction (Blink reflex) | Inclusion (T0) | 
| Delay of silent period | Delay of silent period while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex) | Inclusion (T0) | 
| Duration of silent period | Duration of silent period while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex) | Inclusion (T0) | 
| Inhibition rate | Inhibition rate while the patient is asked to tighten the jaws (Masseter Inhibitory Reflex) | Inclusion (T0) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Brainstem, Electrophysiology