Neuropsychological Sequelae and Long COVID-19 Fatigue

Study Overview
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Brief Summary
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An association of fatigue with post-viral neuropsychological disturbs has been reported. Among patients hospitalized with COVID-19 there is an increased incidence of anxiety and depression symptoms. In addition, a quarter of patients experience at least mild symptoms of acute post traumatic stress disorder. (Mazza, M. G. et al 2020). The prevalence of chronic fatigue syndrome had a correlation with post-traumatic stress disorder (PTSD) in a study conducted after the outbreak of the COVID-19 in Iran (Silmani et al, 2021), that showed 5.8% of subjects suffering from PTSD after 6 months of SARS-CoV-2 infection onset. In this Study we propose to use a tool to quantify the degree of physical and psychological fatigue in post-COVID-19 patients, and assess the correlation of fatigue with the neuropsychiatric sequelae in hospitalized and non hospitalized patients.

Detailed Description
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This study will address the neuropsychiatric sequelae that remain for at least 6 months after SARS-CoV-2 acute infection, as depression, anxiety and/or post-traumatic stress disorder. The patiensts will be assessed at the post-COVID-19 outpatient clinics of five Portuguese Hospitals. In the first visit (T1) will be collected the demographic characteristics; the medical history; and the screening of acute disease symptoms and severity. In the second visit (T2), the time frame will be at least 6 months after the positive test and no longer than 9 months, a set of structured questionnaires will be provided, including: the Chalder Fatigue Scale, Anxiety and Depression Hospital Scale (HADS), The Posttraumatic Stress Symptoms-14 (PTSS-14) adapted to COVID-19 and the EuroQol 5-Dimensions (EQ-5D).

Official Title
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Neuropsychological Sequelae as a Risk Factor for Long COVID-19 Fatigue

Conditions
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Anxiety Depression, Post Traumatic Stress Disorder, Mental Fatigue, COVID-19, Fatigue Syndrome, Chronic

Intervention / Treatment
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* Other: Neuropsychological Sequelae


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years; Previous COVID-19 at least six months after the diagnosis duly documented in the clinical record; Persistent symptoms after cure criteria defined by WHO Symptomatic patients that attend the post-COVID-19 follow-up consultation of the study centres. SARS-CoV-2 RNA confirmed by a positive real-time reverse-transcription polymerase chain reaction on a nasopharyngeal swab. SARS-CoV-2 antigen confirmed on a nasopharyngeal swab, by a healthcare professional. Exclusion Criteria: Patients with PTSD previous diagnosis Severe psychiatric disorders documented in the clinical record Patients not able to respond the questionnaire Patients who had a concomitant severe neurological disorder Clinical and radiological diagnosis of Stroke with sequelae Clinical diagnosis of Alzheimer's Disease Clinical diagnosis of Parkinson's disease Patients with persistent fatigue symptoms in the 6 months before SARS-CoV 2 infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neuropsychological Sequelae<br>Post-COVID-19 symptomatic patients with neuropsychological sequelae | Other: Neuropsychological Sequelae<br>* Neuropsychological Sequelae after SARS-CoV-2 symtomatic infection<br>|
| Without Neuropsychological Sequelae<br>Post-COVID-19 symptomatic patients Without neuropsychological sequelae | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of fatigue in patients with post-COVID-19 depression and/or anxiety | Fatigue will be assessed with the Chalder fatigue scale: - Global score (0-33), that also spans two dimensions-physical fatigue (measured by items 1-7) and psychological fatigue (measured by items 8-11). This is a Likert scoring system that allows for means and distributions to be calculated for both the global total as well as the two sub-scales. Depression and anxiety will be assessed with the Hospital Anxiety and Depression Scale Depression HADS subscale scoring: Normal 0-7; Boderline abnormal 8-10; Abnormal 11-21 Anxiety HADS subscale scoring: Normal 0-7; Borderline 8-10; Abnormal 11-21 | 6-9 months | 
| Prevalence of fatigue in patients with post-COVID-19 post-traumatic stress disorder | Fatigue will be assessed with the Chalder fatigue scale (global and binary score). PTSD will be assessed with the Post-Traumatic Stress Syndrome 14 Questions Inventory (PTSS-14) adapted to COVID-19: - Positive case between 46-98 points | 6-9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of post-COVID-19 fatigue in quality of life. | Fatigue will be assessed with the Chalder fatigue scale (binary score and global score). Quality of live will be assessed by the original EQ-5D questionnaire, that comprises two parts: - EQ-5D-3L, health state classification scheme of five items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each having three alternatives (1= no problems, 2= moderate problems, and 3= severe problems). Calculating a single index score combines these five dimensions. The index value of a particular health state thus indicates the preference for being in that health state in relation to death, which has been set equal to 0 and best possible health (eg, no problems on any of the five items) which has been set to 1.0. - EQ VAS, a visual analog scale to health state ranging from 0 (worst possible health state) to 100 (best possible health state). | 6-9 months | 
| Impact of post-COVID-19 neuropsychological sequelae in quality of life | Evaluate if the positive cases for anxiety, depression and/or PTSD have lower quality of live (The tools will be the same of previous outcomes). | 6-9 months | 
| Evaluate if neuropsychological are associated with severity of acute COVID-19 | Depression and anxiety will be assessed with the Hospital Anxiety and Depression Scale Depression HADS subscale scoring: Normal 0-7; Boderline abnormal 8-10; Abnormal 11-21 Anxiety HADS subscale scoring: Normal 0-7; Borderline 8-10; Abnormal 11-21 Posttraumatic Stress Symptoms-14 instrument, adapted in this protocol for COVID-19 survivors: - PTSS 14 scoring > 45 points Acute COVID-19 severity will be categorized as mild illness (mild symptoms without the radiographic appearance of pneumonia), pneumonia (having symptoms and the radiographic evidence of pneumonia, with no requirement for supplemental oxygen), severe pneumonia (having pneumonia, including one of the following: respiratory rate > 30 breaths/minute; severe respiratory distress; or SpO2 ≤ 93% on room air at rest), and critical cases (e.g. respiratory failure requiring mechanical ventilation or nasal high flow oxygen, septic shock, other organ failure occurrence or admission into the ICU). | 6-9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, fatigue, psychological disorders