Neurodegeneration Markers and Neurological Course in Severe Covid-19 Infection
Keywords
Abstract
Description
In animals, coronavirus infection is commonly associated with CNS involvement:
epilepsy and ataxia are observed during Feline Infectious Peritonitis (FIP) and virus is recovered in CSF, CNS is involved with strain-dependent severity in mice and rats infected by murine hepatitis virus, and murine infection with MHV A59 strain is a model of multiple sclerosis (MS). Mice encephalitis occurs through infection of olfactory bulb and spreads along the axonal pathway. Viral antigens and neuronal apoptosis are observed in brainstem and hypothalamus, without minimal or absent inflammation.
Most COVID-19 patients with neurologic impairment displayed expected complications of severe infections (e.g. neuropathy and muscle loss, stroke) but encephalitis remained exceptional, as previously observed in SRAS. It is argued that central lesions may explain some of the clinical features ventilation failure, or disproportionate residual fatigue and cognition impairment in survivors of severe COVID infection. According to data obtained from various coronavirus infections in animals, the investigators ask if severe COVID infection in human could be associated with sub-clinical encephalitis. This clinical trial examines highly sensitive blood biomarkers of brain dysfunction in correlation with late clinical outcome. Biomarkers are neurofilament light chain (NFL) and GFAP. Clinical outcomes are death, signs of central neurologic sequellae, and fatigue. Clinical examination and blood samples will be obtained at inclusion (d0), which is mostly the entrance in intensive care unit (ICU), at day 7 (between day 4 and exit from ICU) and at day 60.
Dates
| Last Verified: | 04/30/2020 |
| First Submitted: | 04/15/2020 |
| Estimated Enrollment Submitted: | 04/22/2020 |
| First Posted: | 04/23/2020 |
| Last Update Submitted: | 05/18/2020 |
| Last Update Posted: | 05/20/2020 |
| Actual Study Start Date: | 05/18/2020 |
| Estimated Primary Completion Date: | 01/18/2021 |
| Estimated Study Completion Date: | 01/18/2021 |
Condition or disease
Intervention/treatment
Biological: blood samples
Phase
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Infection with Covid-19 (proven or probable) AND - possible encephalitis (at least confusion, epilepsy) OR - clinical severity requiring invasive ventilation. Exclusion Criteria: - brain stroke - minor CNS dysfunction (isolated smell loss or headache), - absence of Covid infection. |
Outcome
Primary Outcome Measures
1. Change of neurodegeneration markers level [Level of neurofilament light chain (NFL) is dosed at inclusion (day 0) and week 1. Level of GFAP is dosed at inclusion (day 0) and week 1 (day 7).]
