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Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium

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To identify the key insights or developments described in this article
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Key Points

Question  What are the incidence of and outcomes associated with neurologic manifestations in patients with COVID-19?

Findings  In this cohort study of 3744 patients in 2 large consortia, neurological manifestations were found in approximately 80% of patients hospitalized with COVID-19; the most common self-reported symptoms included headache (37%) and anosmia or ageusia (26%), whereas the most common neurological signs and/or syndromes were acute encephalopathy (49%), coma (17%), and stroke (6%). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death.

Meaning  These findings suggest that neurological manifestations are prevalent among patients hospitalized with COVID-19 and are associated with higher in-hospital mortality.

Abstract

Importance  The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome.

Objective  To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19.

Design, Setting, and Participants  This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation.

Exposures  Clinically diagnosed or laboratory-confirmed COVID-19.

Main Outcomes and Measures  Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality.

Results  Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19.

Conclusions and Relevance  In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19.

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Article Information

Accepted for Publication: March 15, 2021.

Published: May 11, 2021. doi:10.1001/jamanetworkopen.2021.12131

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Chou SHY et al. JAMA Network Open.

Corresponding Author: Sherry H-Y. Chou, MD, MSc , Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 3550 Terrace St, Scaife Hall 646, Pittsburgh, PA 15261 (hsc36@pitt.edu).

Author Contributions: Dr Chou had full access to all of the data in the Global Consortium Study of Neurological Manifestations of COVID-19 cohort, and Dr Helbok had full access to all of the data in the European Academy of Neurology Neuro-COVID Registry. They take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Chou, Beghi, Helbok, Moro, Altamirano, Mainali, Bassetti, Suarez, McNett.

Acquisition, analysis, or interpretation of data: Chou, Beghi, Helbok, Moro, Sampson, Altamirano, Mainali, McNett.

Drafting of the manuscript: Chou, Beghi, Helbok, Sampson, Mainali, Suarez, McNett.

Critical revision of the manuscript for important intellectual content: Chou, Beghi, Helbok, Moro, Altamirano, Mainali, Bassetti, McNett.

Statistical analysis: Chou, Beghi, Sampson, Altamirano, McNett.

Obtained funding: Chou.

Administrative, technical, or material support: Chou, Helbok, Altamirano, McNett.

Supervision: Chou, Beghi, Helbok, Moro, Bassetti, Suarez, McNett.

Conflict of Interest Disclosures: Dr Beghi reported receiving grants from the European Academy of Neurology during the conduct of the study; receiving grants from the Italian Ministry of Health, the American ALS Association, and Swedish Orphan Biuvitrun and receiving personal fees from Arvelle Therapeutics outside the submitted work. Dr Moro reported receiving personal fees from Medtronic and Newronika and receiving grants from Ipsen outside the submitted work. Dr Mainali reported receiving grants from the Center for Clinical and Translational Science at the Ohio State University, sponsored by a National Center for Advancing Translational Sciences Award, outside the submitted work. No other disclosures were reported.

Funding/Support: This publication was supported by the National Institutes of Health, National Center for Advancing Translational Sciences through grant UL1 TR001857 to the University of Pittsburgh and Dr Chou, the National Institute of Health through grant R21NS113037 to Dr Chou, and the University of Pittsburgh Dean’s Faculty Advancement Award to Dr Chou. Data collection for the European registry was supported by the European Academy of Neurology.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Members: The GCS-NeuroCOVID Consortium and the ENERGY Consortium members appear in Supplement 2.

Additional Information: The study protocol and case report forms have been previously published and are currently available.24,27,28 Deidentified data may be available at the conclusion of all studies of either consortia by request for specific scientific investigations and meta-analyses, at the discretion of the data coordinating centers for each respective consortium and in accordance with applicable privacy laws and data use agreements.

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