Ummehan Ermis1, Marcus Immanuel Rust2, Julia Bungenberg2, Ana Costa2, Michael Dreher3, Paul Balfanz4, Gernot Marx5, Martin Wiesmann6, Kathrin Reetz2,7, Simone C Tauber2, Jörg B Schulz2,7. 1. Department of Neurology, RWTH University Hospital, Aachen, Germany. uermis@ukaachen.de. 2. Department of Neurology, RWTH University Hospital, Aachen, Germany. 3. Department of Pneumonology and Internal Intensive Care Medicine, RWTH University Hospital, Aachen, Germany. 4. Department of Cardiology, Angiology and Internal Intensive Care Medicine, RWTH University Hospital, Aachen, Germany. 5. Department of Operative Intensive und Intermediate Care Medicine, RWTH University Hospital, Aachen, Germany. 6. Department of Diagnostic and Interventional Neuroradiology, RWTH University Hospital, Aachen, Germany. 7. JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH University Hospital, Aachen, Germany.
Abstract
BACKGROUND: The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany. METHODS: Between March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS). RESULTS: Major clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR. CONCLUSIONS: In line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.
BACKGROUND: The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany. METHODS: Between March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically illpatients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS). RESULTS: Major clinical neurological features of hospitalized COVID-19patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR. CONCLUSIONS: In line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.
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