Neurological and Neuropsychological Sequelae of COVID-19 Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 329
- 试验地点
- 3
- 主要终点
- Deficits in cognition
研究概览
简要总结
COVID-19 is known to affect the respiratory system but may also have an impact on other organ systems, including the brain. A number of severely ill patients also presents neurological symptoms that may be the result of COVID-19 associated brain damage. The aim of this study is to investigate the presence, type, and severity of brain damage as well as the neurological and neuropsychological sequelae of COVID-19 infection. Further, the impact of this infection on daily life functioning, quality of life, and the emotional well-being of family members will be assessed. In this multicenter study, 6-9 months after hospital discharge patients will undergo a 3-T MRI scan and a neuropsychological examination. Additionally, both patients and their family members will answer several questionnaires at 6- 9 and 12-15 months after hospital discharge. COVID-19 patients previously admitted to a general hospital ward will be compared with patients previously admitted to the intensive-care unit. The proposed study will create a more comprehensive picture of the prolonged COVID-19 effects on the brain, mental, and cognitive well-being. The findings will aid patient care and rehabilitation.
详细描述
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). COVID-19 primarily affects the respiratory system. However, in severely ill patients damage is also reported to other organ systems including the heart, the kidneys, the circulatory, and gastrointestinal system. Further, research indicates an impact of the virus on the brain and, thereby, on cognition. Patients experience neurological symptoms, MR imaging implies the presence of brain abnormalities, specifically in severely ill patients and studies on cognition suggest problems with memory, attention, information processing and executive function. Preliminary clinical data also show that COVID-19 is associated with neurological and neuropsychiatric illness.
Brain damage and therefrom resulting emotional and cognitive deficits in ICU-treated patients are not uncommon findings. Post-intensive care syndrome (PICS) summarizes physical, cognitive, and mental impairments associated with ICU admission. PICS is assumed to be induced by a combination of patient-specific (e.g., psychiatric history), disease-related (e.g., hypoxemia), and ICU factors (e.g., invasive procedures). These factors can cause a variety of pathophysiologic states including atrophy, encephalopathy, and neuropathy, eventually leading to impairment and reduced quality of life. Additionally, ICU-admission has been found to also affect the mental health of patients´ family members (PICS-F). Many of these PICS-inducing factors can be assumed to occur during severe COVID-19 illness and treatment. Therefore, it is likely that COVID-19 patients and their family members exhibit PICS symptoms.
To date, it is not known to what extend COVID-19 related brain injury and therewith associated symptoms are present after the (sub)acute stages of illness and whether this will lead to long-term deficits in function. Further, it is to be determined whether COVID-19 patients develop PICS syndrome and if so, whether the therewith associated symptoms are limited to ICU-treated patients or may generally affect the broader group of hospitalized COVID-19 patients.
The aim of this research is to fill these gaps in research through:
(1) the identification of COVID-19 related brain abnormalities, cognitive impairments, and emotional deficits after the (sub)acute stages of illness (i.e., 6-9 months post-hospital discharge), 2) a comparison of COVID-19 related brain abnormalities, cognitive impairments, and emotional deficits to historical PICS cohorts 3) a comparison between COVID-19 ICU survivors and COVID-19 non-ICU patients in order to assess a potential PICS gradient and 3) a follow-up examination of the aforementioned groups 6 months after the first assessment to gain insight into the persistence of deficits.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Objectified COVID-19 infection for which ICU or non-ICU hospital admission was necessary at one of the participating hospitals
- •Age > 18 years
- •Sufficient command of the Dutch language to follow test instructions and understand questionnaires
- •Informed consent.
- •Family members (if present):
- •Within the scope of this study, the term family member will be defined as a person who has good insight into the patient´s daily life functioning (before and after COVID-19 infection). This person can be the spouse, partner, adult child or, in some cases, another individual that plays the most significant role in the patient´s life. The patient will decide who this family member is. We will check the following criteria:
- •Family member of a participant with COVID-19 infection as described above;
- •Requires participation of the aforementioned family member as COVID-19 patient
- •Age > 18 years
- •Sufficient command of the Dutch language to understand questionnaires
- •Informed consent.
排除标准
- •objectified cognitive impairments before the hospital admission for the COVID-19 infection
- •an unexpected incident leading to severe neurological damage occurring after hospital discharge (such as stroke or traumatic brain injury)
- •contra-indications for MRI scanning (e.g. metal implants, cardiac pacemaker, claustrophobia, pregnancy).
- •Family member: no exclusion criteria.
结局指标
主要结局
Deficits in cognition
时间窗: 6-9 months after hospital discharge
Deficits in general cognition are measured with the Montreal Cognitive Assessment (MoCA).
Change in patient quality of life
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Quality of life measured by the EuroQol-5D-5L (EQ-5D-5L). The EQ-5D-5L consists of 5 items with 5 levels. The minimum total score is 5 and the maximum total score is 25, with higher scores indicating more problems.
Change in post-traumatic stress symptoms
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Measured with the Primary Care Post-Traumatic Stress Disorder (PC-PTSD-5) questionnaire
Change in family quality of life
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Measured by the EQ-5D-5L. The EQ-5D-5L consists of 5 items with 5 levels. The minimum total score is 5 and the maximum total score is 25, with higher scores indicating more problems.
Deficits in working memory, attention & executive function
时间窗: 6-9 months after hospital discharge
Measured with Digit Span Coding
Presence of MRI abnormalities
时间窗: 6-9 months after hospital discharge
Presence or absence of MRI abnormalities assessed with a 3T cranial MRI scan
Deficits in visual attention & task switching
时间窗: 6-9 months after hospital discharge
Measured with Trail Making Test A/B (TMT)
Deficits in selective attention, cognitive flexibility & processing speed
时间窗: 6-9 months after hospital discharge
Measured with Stroop Test
Change in depression/anxiety
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Measured with the Hospital anxiety and depression scale
Deficits in memory
时间窗: 6-9 months after hospital discharge
Measured with the Rey's auditory verbal learning test (RAVLT)
Change in subjective cognitive complaints
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Assessed with the Checklist for post-IC cognitive complaints (CLC-IC)
Change in family burden
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Measured with the Caregiver Strain Index (CSI)
Change in participation
时间窗: 1) 6-9 months and 2) 12-15 months after hospital discharge
Life participation (social, occupational, mobility) measured by the Utrecht Scale for Evaluation of Rehabilitation-Participation - Restrictions subscale (USER-P-R). The subscale consists of 11 items. Each item score ranges from 0 (not possible at all) to 3 (no difficulty at all), resulting in a total minimum score of 0 and a total maximum score of 33 points, with a higher score indicating less participation restrictions.
Neurological symptoms
时间窗: 6-9 months after hospital discharge
Measures with the neurological and neuropsychological sequelae of COVID-19 questionnaire (NeNeSCo-Q), a questionnaire that has been created for the purpose of this study to assess the most common neurological symptoms (e.g., reduced sense of taste and/or smell, headaches, neuropathic pain) experienced by patients infected with COVID-19. The questionnaire consists of 9 items being rated with present (yes = 1) and not present (no = 0), resulting in a minimum total score of 0 and a maximum total score of 9.
次要结局
- MRI abnormalities (specific)(6-9 months after hospital discharge)