Vardan Nersesjan1, Moshgan Amiri1, Anne-Mette Lebech2,3, Casper Roed2, Helene Mens2, Lene Russell4, Lise Fonsmark4, Marianne Berntsen5, Sigurdur Thor Sigurdsson5, Jonathan Carlsen6, Annika Reynberg Langkilde6, Pernille Martens6, Eva Løbner Lund7, Klaus Hansen1, Bo Jespersen8, Marie Norsker Folke9, Per Meden9, Anne-Mette Hejl9, Christian Wamberg10, Michael E Benros11,12, Daniel Kondziella13,14. 1. Departments of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2. Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Department of Neuroanesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Radiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 7. Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 8. Department of Neurosurgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 9. Department of Neurology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 10. Department of Anesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 11. Copenhagen Research Centre for Mental Health, CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Hellerup, Denmark. michael.eriksen.benros@regionh.dk. 12. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. michael.eriksen.benros@regionh.dk. 13. Departments of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. daniel.kondziella@regionh.dk. 14. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. daniel.kondziella@regionh.dk.
Abstract
OBJECTIVE: To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19 patients. METHODS: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related. RESULTS: From April to September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (n = 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR = 1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated. CONCLUSION: CNS and PNS complications were common in hospitalized COVID-19 patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.
OBJECTIVE: To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19patients. METHODS: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related. RESULTS: From April to September 2020, we enrolled 61 consecutively admitted COVID-19patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (n = 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR = 1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated. CONCLUSION: CNS and PNS complications were common in hospitalized COVID-19patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.
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