COVID-19 Neurological Disease: A Prospective Study

NCT04672590 | Completed

• 1 other identifier: UoL001596
• Study Type: observational
• Target: 1,017
• Locations: 3 countries
• Sites: 5

Brief Summary

Background: Recent reports increasingly recognize neurological manifestations in COVID-19 patients. However, the full spectrum of the disease and risk factors are not well understood. Aim: To describe the full spectrum of neurological manifestations in COVID-19 and assess the clinical characteristics, risks and prognostic factors. Outcomes: Identification of COVID-19 associated neurological disease is the primary outcome while requirement for admission to critical care unit, mortality, length of hospital stay, quality of life, and neurological disability are the secondary outcomes. Participants: Patients above Age more than 18 years enrolled based on new-onset acute neurological disease and COVID19 positive will serve as cases while patient with confirmed COVID-19 without neurological manifestation will serve as controls. Design and Procedures: The study is prospective case control in design and is divided into three phases in India, Brazil and Malawi ; the first phase will address role of hypoxia in causation of neurological diseases, the second phase will compare characteristics of patients hospitalized with COVID-19 with and without neurological disease and the third phase will assess the long-term follow up (at 3 months and 9 months) of cases.

Conditions

Diseases of the Nervous System; Other Specified Viral Diseases

Outcome Measures

Primary Outcomes (1)

• Acute new-onset neurological disease

  Day 30 of admission, or at discharge, or at death, whichever is earlier

Secondary Outcomes (9)

• Admission to a critical (intensive/high dependency) care unit

  Day 30 of admission, or at discharge, or at death, whichever is earlier

• Time to discharge from hospital

  Day 30 of admission, or at discharge, or at death, whichever is earlier

• Severity of stroke using National Institutes of Health Stroke Scale (NIHSS)

  Day 30 of admission, or at discharge, or at death, whichever is earlier

• Glasgow Outcome Scale Extended

  Discharge (or day 30), 3 months and 9 months

• Modified Rankin Score

  Discharge (or day 30), 3 months and 9 months

Study Arms (2)

Cases

Patients admitted to a study hospital meeting criteria for confirmed or probable acute new-onset neurological disease and confirmed or probable COVID-19.

Other: Primary exposure is hypoxia (no intervention)

Controls

Patients admitted to a study hospital meeting criteria for confirmed or probable COVID-19, without confirmed or probable acute new-onset neurological disease.

Other: Primary exposure is hypoxia (no intervention)

Interventions

Primary exposure is hypoxia (no intervention) OTHER

The primary exposure, hypoxia, will be defined as severe, non-severe or none for each participant, based on pre-defined criteria.

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cases: Hospitalised patients with acute new-onset neurological disease and COVID-19 Controls: Hospitalised patients with COVID-19, without acute new-onset neurological disease

You may qualify if:

• Confirmed or probable new-onset acute neurological disease (according to study definitions) AND
• Confirmed or probable COVID-19 (according to study definitions), diagnosed using tests performed no later than 5 days after presentation with neurological disease

You may not qualify if:

• Age \<18 years
• Neurological features are explained fully by a previous neurological disease
• PCR test performed \>5 days after admission to hospital, in the absence of clinical illness meeting criteria for suspected COVID-19 (to exclude those with hospital-acquired infection).
• Enrolled on the basis of new-onset acute neurological disease, but subsequently does not meet definition for probable or confirmed COVID-19.
• Controls
• Two controls with non-neurological COVID-19 will be recruited per case.
• They will meet all of the following criteria:
• Adults, no more than 5 years younger or older than the case.
• Enrolled at a similar time since admission to hospital as the case, defined as: \<7 days; 7-13 days inclusive; or ≥14 days.
• Hospitalised patients with confirmed or probable COVID-19 (according to study definitions)
• Not meeting criteria for confirmed or probable new-onset acute neurological disease (according to study definitions).
• Some potential controls may be reclassified as cases if they develop neurological manifestations at up to 30 days after admission to hospital.

Sponsors & Collaborators

• University of Liverpool: lead
• Christian Medical College, Vellore, India: collaborator
• Instituto Autoimune, Brazil: collaborator
• University College London Hospitals: collaborator
• Oswaldo Cruz Foundation: collaborator
• Kamuzu University of Health Sciences: collaborator
• National Institute of Mental Health and Neuro Sciences, India: collaborator
• Encephalitis Society, UK: collaborator

Study Sites (5)

FioCruz

Recife, Brazil

Location

National Institute of Mental Health and Neurosciences

Bangalore, India

Location

Christian Medical College

Vellore, India

Location

Malawi Liverpool Wellcome Clinical Research Programme

Blantyre, PO Box 30096, Malawi

Location

Kamuzu University of Health Sciences

Blantyre, PO Box 360, Malawi

Location

MeSH Terms

Conditions

Nervous System Diseases

Study Officials

• Tom Solomon, PhD

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 17, 2020
• Study Start: April 20, 2021
• Primary Completion: March 31, 2023
• Study Completion: December 31, 2024
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

IN (2); BR (1); MA (2)