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.

Nervous System Involvement in Coronavirus Disease 2019: Results from a Retrospective Consecutive Neuroimaging Cohort.

Background Neurologic complications in coronavirus disease 2019 (COVID-19) have been described, but the understanding of their pathophysiologic causes and neuroanatomical correlates remains limited. Purpose To report on the frequency and type of neuroradiological findings in COVID-19. Materials and Methods In this retrospective study, all consecutive adult hospitalized patients with polymerase chain reaction positivity for severe acute respiratory syndrome coronavirus 2 and who underwent neuroimaging at Karolinska University Hospital between March 2 and May 24, 2020, were included. All examinations were systematically re-evaluated by 12 readers. Summary descriptive statistics were calculated. Results A total of 185 patients with COVID-19 (62 years ± 14 [standard deviation]; 138 men) underwent neuroimaging. In total, 222 brain CT, 47 brain MRI, and seven spinal MRI examinations were performed. Intra-axial susceptibility abnormalities were the most common finding (29 of 39; 74%, 95% CI: 58, 87) in patients who underwent brain MRI, often with an ovoid shape suggestive of microvascular pathology and with a predilection for the corpus callosum (23 of 39; 59%; 95% CI: 42, 74) and juxtacortical areas (14 of 39; 36%; 95% CI: 21, 53). Ischemic and macrohemorrhagic manifestations were also observed, but vascular imaging did not demonstrate overt abnormalities. Dynamic susceptibility contrast perfusion MRI in 19 patients did not reveal consistent asymmetries between hemispheres or regions. Many patients (18 of 41; 44%; 95% CI: 28, 60) had leukoencephalopathy and one patient had a cytotoxic lesion of the corpus callosum. Other findings included olfactory bulb signal abnormalities (seven of 37; 19%), prominent optic nerve subarachnoid spaces (20 of 36; 56%), and enhancement of the parenchyma (three of 20; 15%), leptomeninges (three of 20; 15%), cranial nerves (two of 20; 10%), and spinal nerves (two of four; 50%). At MRI follow-up, regression of leukoencephalopathy and progressive leptomeningeal enhancement was observed in one patient each, respectively, which is suggestive of dynamic processes. Conclusion Patients with coronavirus disease 2019 had a wide spectrum of vascular and inflammatory involvement of both the central and peripheral nervous system. © RSNA, 2020 Online supplemental material is available for this article.

Neurological manifestations of coronavirus infections - a systematic review.

To optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until 26 July 2020) using systematic searches in PubMed, Web of Science, and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1, and SARS-CoV-2). Moreover there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache, and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain-Barré syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures, and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs.