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

Sherry Chou(University of Pittsburgh), Ettore Beghi(Mario Negri Institute for Pharmacological Research), Raimund Helbok(Innsbruck Medical University), Elena Moro(Centre Hospitalier Universitaire de Grenoble), Joshua N. Sampson(National Cancer Institute), Valeria Altamirano(University of Pittsburgh), Shraddha Mainali(The Ohio State University), Claudio L. Bassetti(University of Bern), José I. Suárez(Johns Hopkins University), Molly McNett(The Ohio State University), Lawrence Nolan(Clinical Research Consortium), Kristi Temro(Clinical Research Consortium), Anna M. Cervantes‐Arslanian(Clinical Research Consortium), Pria Anand(Clinical Research Consortium), Shibani S. Mukerji(Clinical Research Consortium), Haitham Alabasi(Clinical Research Consortium), M. Brandon Westover(Clinical Research Consortium), Tapan Kavi(Clinical Research Consortium), Sayona John(Clinical Research Consortium), Ivan Da Silva(Clinical Research Consortium), Arif Pasha Shaik(Clinical Research Consortium), Aarti Sarwal(Clinical Research Consortium), Saef Izzy(Clinical Research Consortium), Eric M. Liotta(Clinical Research Consortium), Ayush Batra(Clinical Research Consortium), Aimee Aysenne(Clinical Research Consortium), Clio Rubiños(Clinical Research Consortium), Ahmed Y. Azzam(Clinical Research Consortium), Mohammed A. Azab(Clinical Research Consortium), Justin Sandall(Clinical Research Consortium), LeighAnn Persondek(Clinical Research Consortium), Hanno Ulmer(Clinical Research Consortium), Verena Rass(Clinical Research Consortium), Bettina Pfausler(Clinical Research Consortium), Christoph Müller(Clinical Research Consortium), Simon Jung(Clinical Research Consortium), Michael Crean(Clinical Research Consortium), Sara Meoni(Clinical Research Consortium), Dániel Bereczki(Clinical Research Consortium), Tibor Kovács(Clinical Research Consortium), Netta Agajany(Clinical Research Consortium), Carmel Armon(Clinical Research Consortium), Sharon Wolfson(Clinical Research Consortium), Maria Sofia Cotelli(Clinical Research Consortium), Elisa Bianchi(Clinical Research Consortium), A. Riahi(Clinical Research Consortium), Şerefnur Öztürk(Clinical Research Consortium), Onur Ural(Clinical Research Consortium), Gryb Viktoriia(Clinical Research Consortium), M. I. Lesiv(Clinical Research Consortium), Luı́s F. Maia(Clinical Research Consortium), Vanessa Oliveira(Clinical Research Consortium), Mafalda Seabra(Clinical Research Consortium), Vanessa Carvalho(Clinical Research Consortium), Paul Vespa(Clinical Research Consortium), J. Javier Provencio(Clinical Research Consortium), DaiWai M. Olson(Clinical Research Consortium), Claude Hemphill(Clinical Research Consortium), Chethan P. Venkatasubba Rao(Clinical Research Consortium), Nerissa Ko(Clinical Research Consortium), Ericka L. Fink(Clinical Research Consortium), Courtney Robertson(Clinical Research Consortium), Michelle E. Schober(Clinical Research Consortium), Ali Scott(Clinical Research Consortium), Michal Hammond(Clinical Research Consortium), Nicole Paul(Clinical Research Consortium), Aleksandra Safonova(Clinical Research Consortium), L. Kaplan(Clinical Research Consortium), Charith Ratnayake(Clinical Research Consortium), Adytia D Sharma(Clinical Research Consortium), Abigail Skeel(Clinical Research Consortium), Carlos Villamizar Rosales(Clinical Research Consortium), Dominika Dolak(Clinical Research Consortium), Panayiotis N. Varelas(Clinical Research Consortium), Lev Lotman(Clinical Research Consortium), L Kaltenbach(Clinical Research Consortium), Menon David K.(Clinical Research Consortium)
JAMA Network Open
May 11, 2021
Cited by 415Open Access
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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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