COVID-19 Prevalence and Cognitive Deficits in Neurological Patients

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

Detailed Description
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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.

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

Conditions
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Neurological Diseases or Conditions, Stroke, Acute, Seizure Disorder

Intervention / Treatment
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* Diagnostic Test: COVID-19 swap test PCR


Participation Criteria
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Eligibility Criteria
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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

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with acute neurological symptoms<br>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<br>* COVID-19 swap test PCR performed according to hospital standard operating procedures<br>|
| Stroke patients<br>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<br>* COVID-19 swap test PCR performed according to hospital standard operating procedures<br>|
| Seizure/epilepsy<br>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<br>* COVID-19 swap test PCR performed according to hospital standard operating procedures<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevalence, COVID-19, Neurological disease, Cognitive outcome, Stroke, Seizure/epilepsy