COVID-19 Neurological Disease: A Prospective Study

COVID-19 Neurological Disease: A Prospective Study in Brazil, India and Malawi

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diseases of the Nervous System; Other Specified Viral Diseases
• Intervention / Treatment: Other: Primary exposure is hypoxia (no intervention)

• Study Type: Observational
• Enrollment (Estimated): 681

Contacts and Locations

• Study Contact: Name: Bhagteshwar Singh, MRCP; Phone Number: +441517957577; Email: bsingh@liverpool.ac.uk

Study Locations

• Brazil
  • Recife, Brazil
    • FIOCRUZ
• India
  • Bangalore, India
    • National Institute of Mental Health and Neurosciences
  • Vellore, India
    • Christian medical college
• Malawi
  • Blantyre, Malawi, PO Box 30096
    • Malawi Liverpool Wellcome Clinical Research Programme
  • Blantyre, Malawi, PO Box 360
    • Kamuzu University of Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

Cases

Inclusion criteria:

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

Exclusion criteria (any of):

• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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); The primary exposure, hypoxia, will be defined as severe, non-severe or none for each participant, based on pre-defined criteria.
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); The primary exposure, hypoxia, will be defined as severe, non-severe or none for each participant, based on pre-defined criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Acute new-onset neurological disease	Day 30 of admission, or at discharge, or at death, whichever is earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	A score made up of 11 elements. Total min 0; max 42. Lower is better; 0 can be scored if the person has full function in every element of the assessment.	Day 30 of admission, or at discharge, or at death, whichever is earlier
Glasgow Outcome Scale Extended	An ordinal scale, from 1 = death (minimum; worst outcome) to 8 = upper good recovery (maximum; best outcome).	Discharge (or day 30), 3 months and 9 months
Modified Rankin Score	Modified Rankin Score using a simplified algorithm by Bruno et al 2010. An ordinal scale, from 0 = no symptoms at all (minimum; best outcome) to 6 = dead (maximum; worst outcome).	Discharge (or day 30), 3 months and 9 months
Montreal Cognitive Assessment (MoCA)	Montreal Cognitive Assessment (MoCA), using a full test at discharge (or day 30) and a telephone test at 3 months and 9 months	Discharge (or day 30), 3 months and 9 months
Development of new onset neurological sequelae	Development of new onset neurological sequelae e.g.epilepsy, new/recurrent stroke, cognitive decline, encephalitis	Discharge (or day 30), 3 months and 9 months
European QoL-5D (EQ-5D-3L) overall health utility quality of life score	A questionnaire scoring 5 domains of quality of life at ordinal levels of 1-3 each (1 = best; 3 = worst), plus an overall health state score from 0 to 100 on a visual analog scale (0 = worst; 100 = best).	Discharge (or day 30), 3 months and 9 months
Death		In-hospital (up to 30 days from admission), and at 3 months and 9 months

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: University College London Hospitals; Oswaldo Cruz Foundation; Kamuzu University of Health Sciences; Christian Medical College, Vellore, India; National Institute of Mental Health and Neuro Sciences, India; Instituto Autoimune, Brazil; Encephalitis Society, UK
• Investigators: Principal Investigator: Tom Solomon, PhD, University of Liverpool

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; Nervous System Diseases
• Other Study ID Numbers: UoL001596

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Limited dataset

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No