Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients

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.

Keywords: COVID-19; Cognitive impairment; Neuro-invasive potential; Neurological symptoms; SARS-CoV-2.

Fig. 1

Exemplary cranial CT scans with diffuse sulcal/subarachnoidal bleedings frontally, frontobasally and parietally (wide arrows), and partly confluent frontobasal and subcortical hypodensities (slim arrows) indicating infarction in a a 48 year-old male (patient #39) and b a 56 year-old male (patient #37) with both severe COVID-19 and acute respiratory distress syndrome

Fig. 2

Exemplary MR imaging with multiple spotted (a) or confluent (b) hyperdense lesions (arrow) on axial fluid-attenuated inversion recovery (FLAIR) partly with contrast enhancement (circle) in the basal ganglia (b). Furthermore, evidence of multiple microbleeds in T2* sequences with emphasis on the corpus callosum (c) and the white matter as well as multiple cortical sulcal hemorrhages (e) and proof of ventricular hemorrhage (f). a-c 62 year-old female (patient #2) and d-f: 69 year-old male (patient #32), both with severe COVID-19 and acute respiratory distress syndrome