COVID-19 Prevalence and Cognitive Deficits in Neurological Patients (Neuro-Covid)

COVID-19 Prevalence, Morbidity and Long Term Cognitive Deficits in Consecutive Patients Presenting With Acute Neurological Symptoms

The purpose is to investigate the COVID-19 prevalence, associated morbidity and long-term cognitive deficits in consecutive patients presenting with acute neurological symptoms

Study Overview

• Status: Withdrawn
• Conditions: Stroke, Acute; Seizure Disorder; Neurological Diseases or Conditions
• Intervention / Treatment: Diagnostic test: COVID-19 swap test PCR

Detailed Description

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading in nearly every country in the world. Patients with coronavirus disease 2019 (COVID-19) typically present with cough, fever and respiratory illness. In another coronavirus (SARS-COV-1) causing the SARS outbreak in 2002 to 2003, neurons have been found to be highly susceptible for infection and the virus can cause extensive neuronal damage with only minimal respiratory affection. Similar to SARS-CoV-1, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE-2) receptor to gain entry and infect cells. Both glial and neurons express ACE-2 receptors and makes them potential targets, however the neurotropic potential in humans remain largely undescribed. Neurological manifestations of COVID-19 have only been sporadically described in single or short series of case reports together with a case of COVID-19 RNA in the cerebrospinal fluid.

Loss of smell (anosmia) may be a presenting symptom in COVID-19. Interestingly, in a study from Italy anosmia was present in 19,4% and not typical accompanied by nasal obstruction, rhinitis or sinusitis, making direct damage and invasion of the olfactory nerve more likely. A Chinese study have found that 36.6% of COVID-19 patients experience neurological symptoms and that severely affected COVID-19 patients reported more neurological symptoms.

In general, neurological manifestations to viral disease may occur as a direct result of viral invasion and damage to either the central or peripheral nervous system or from an immune mediated neurological damage either during (para) or after (post) the viral infection. Furthermore, the inflammation in itself can increase the risk of arterial thrombosis and thus ischemic stroke.

Early reports from Italy stresses the need to pay attention to neurological symptoms, as they are often neglected due to the systemic and respiratory impairment. Further, concerning reports from the Center for Disease Control (CDC) in USA, have estimated that out of COVID-19pos patients up to 46.5% may be asymptomatic/pre-symptomatic and 17,5% never develop classical COVID-19 symptoms. The COVID-19 infection is likely to be missed if patients present with symptoms from another organ system. Moreover, it poses a transmission risk for other admitted patients and healthcare workers and a risk that a possible association between e.g. neurological symptoms/diseases and a COVID-19 infection are missed. The role and presence of COVID-19 infection in patients presenting with acute neurological symptoms is currently unknown.

• Study Type: Observational

Contacts and Locations

Study Locations

• Denmark
  • DK
    • Aalborg, DK, Denmark, 9000
      • Aalborg University Hospital
    • Aarhus, DK, Denmark, 8200
      • Aarhus University Hospital
    • Holstebro, DK, Denmark, 7500
      • Regional Hospital West Jutland, Hostebro
    • Viborg, DK, Denmark, 8800
      • Regional Hospital Central Jutland, Viborg

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Base study: Consecutive patients with acute neurological disease admitted at the Neurology department at Aarhus University Hospital will be tested with a nasopharyngeal swap for SARS-COVID-19 RNA

Extended study: Patients fulfilling the extended study criteria will be asked to participate in extended study depending on their COVID-19 status and whether study criteria are fulfilled

Description

Eligibility criteria for the extended study:

Inclusion Criteria:

• Adult patients
• New onset of neurological symptoms
• Independent in daily activities (modified Rankin Scale ≤ 2)
• Stroke or epilepsy/seizure

Exclusion Criteria:

• Pre-existing neurodegenerative disease
• Diagnosed with cerebral neoplasm
• Pre-existing expected life expectancy < 3 months
• Suspected non-organic (functional) disorder

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with acute neurological symptoms; Consecutive patients with acute neurological disease admitted at the Neurology departments will be tested with a nasopharyngeal swap for SARS-COVID-19 RNA according to standard operating procedures at the department (if estimated hospital stay is >24hours). Medical and clinical characteristics will be collected	Diagnostic test: COVID-19 swap test PCR; COVID-19 swap test PCR performed according to hospital standard operating procedures
Stroke patients; COVID-19 positive patients will be asked to participate in the extended study together with matched COVID-19 negative controls. Extended study: Collection of cerebrospinal fluid and blood-samples, clinical and cognitive assessment at baseline and at 3-month follow-up	Diagnostic test: COVID-19 swap test PCR; COVID-19 swap test PCR performed according to hospital standard operating procedures
Seizure/epilepsy; COVID-19 positive patients will be asked to participate in the extended study together with matched COVID-19 negative controls. Extended study: Collection of cerebrospinal fluid and blood-samples, clinical and cognitive assessment at baseline and at 3-month follow-up	Diagnostic test: COVID-19 swap test PCR; COVID-19 swap test PCR performed according to hospital standard operating procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of COVID-19 infection in consecutive patients with neurological symptoms	To investigate the prevalence of COVID-19 infections in consecutive patients with acute onset of neurological symptoms (with or without prior neurological disease)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Three months cognitive function of COVID-19 positive patients	Three months cognitive function (Montreal Cognitive Assessment) of COVID-19 positive patients compared to COVID-19 negative patients	3 months
Clinical presentation of neurological symptoms in COVID-19 positive patients	Characterization of the neurological symptoms in neurological COVID-19 positive patients (exploratory endpoint)	6 months
Prevalence of pre- and asymptomatic COVID-19 positive patients in acutely admitted neurological patients	Prevalence of pre-symptomatic and asymptomatic COVID-19pos in acutely admitted patients with a primary complaint of neurological symptoms.	6 months
Anosmia in COVID-19 positive patients	Prevalence of anosmia in COVID-19pos patients compared to COVID-19neg patients	6 months
Exploratory analysis on neuro-specific and inflammatory blood and cerebrospinal fluid markers of COVID-19 infection	Neuro-specific and inflammatory blood- and cerebrospinal fluid markers in COVID-19 positive patients compared to COVID-19 negative matched controls	24 months
Exploratory analysis of the coagulation profile of COVID-19 positive patients compared to COVID-19neg patients	Functional and immunologic plasma assays will be employed to analyze proteins and pathways in coagulation and fibrinolysis	24 months

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Investigators: Principal Investigator: Grethe Andersen, MD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 7, 2020
• Primary Completion (Anticipated): November 29, 2020
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Stroke; Prevalence; COVID-19; Cognitive outcome; Neurological disease; Seizure/epilepsy
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurologic Manifestations; Neurocognitive Disorders; Stroke; Epilepsy; COVID-19; Nervous System Diseases; Cognitive Dysfunction; Seizures; Cognition Disorders
• Other Study ID Numbers: Neuro-Covid-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Upon reasonable request

Drug and device information, study documents

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