The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors.

BACKGROUND: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. METHODS: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. RESULTS: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. CONCLUSION: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

Neuro-COVID: Does severe COVID-19 infection increase the risk for cognitive impairment?

Background Neurocognitive manifestations of the coronavirus disease 2019 (COVID-19) have been reported in the acute phase, especially in critically ill patients. The potential mechanisms underlying these symptoms are not fully understood but probably involves the inflammatory, vascular, and neurotropic effect of the coronavirus. While short-, mid-and long-term consequences remain unclear, patients with neurocognitive sequelae reminiscent of other cognitive disorders, including AD have been reported. The aim of this study is to investigate if there is an increased risk for long-term cognitive dysfunction/impairment, biochemical and structural brain changes after a severe COVID-19. Method This is a prospective cohort study of 80 patients surviving intensive-care for COVID-19 at Karolinska University Hospital, Stockholm, Sweden. They will be examined at 3, 6 and 12 months after hospital discharge using neurological and neuropsychological (NP) tests combined with novel quantitative brain MRI and serial blood sampling to described relevant blood-borne molecular patterns. This presentation focuses on NP testing, cognitive, mental, and neurological aspects at 3 months follow-up. Cognitive testing and questionnaires (NP) include Rey Auditory Verbal Learning Test Rey Complex Figure test, Verbal Fluency Test, Category flow, Trail Making Test Symbol Digit Modalities Test, Mental Fatigue Scale, the Hospital Anxiety and Depression Scale, RAND-36, AD8 Dementia Screening Interview and Subjective cognitive decline questions. A detailed neurological examination (neurologist), including Expanded Disability Status Scale, an adapted version of the Unified Parkinson's Disease Rating Scale for extrapyramidal dysfunction, and a brief smell test. Results At present, 28 participants have completed the 3-months follow-up visit, including neuropsychological and neurological examinations. Mean age (SD) at baseline was 57.8 (11.1) years, and 68% were men. Several patients expressed cognitive and/or mental concerns and fatigue. The neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Brain MRI revealed mainly microvascular pathology. Detailed analyses, including blood biomarkers for neuronal injury and astrocytic activation, based on the 3-months examination will be presented. Conclusions Repeated examinations will allow further analyses on longer term impact on cognition and underlying mechanisms. This may identify patients at risk and possible ways to mitigate cognitive complications, which is of great importance to reduce the pandemic's negative effects and socioeconomic burden.