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

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.

The Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Development of Case Report Forms for Global Use.

Since its original report in January 2020, the coronavirus disease 2019 (COVID-19) due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly become one of the deadliest global pandemics. Early reports indicate possible neurological manifestations associated with COVID-19, with symptoms ranging from mild to severe, highly variable prevalence rates, and uncertainty regarding causal or coincidental occurrence of symptoms. As neurological involvement of any systemic disease is frequently associated with adverse effects on morbidity and mortality, obtaining accurate and consistent global data on the extent to which COVID-19 may impact the nervous system is urgently needed. To address this need, investigators from the Neurocritical Care Society launched the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID). The GCS-NeuroCOVID consortium rapidly implemented a Tier 1, pragmatic study to establish phenotypes and prevalence of neurological manifestations of COVID-19. A key component of this global collaboration is development and application of common data elements (CDEs) and definitions to facilitate rigorous and systematic data collection across resource settings. Integration of these elements is critical to reduce heterogeneity of data and allow for future high-quality meta-analyses. The GCS-NeuroCOVID consortium specifically designed these elements to be feasible for clinician investigators during a global pandemic when healthcare systems are likely overwhelmed and resources for research may be limited. Elements include pediatric components and translated versions to facilitate collaboration and data capture in Latin America, one of the epicenters of this global outbreak. In this manuscript, we share the specific data elements, definitions, and rationale for the adult and pediatric CDEs for Tier 1 of the GCS-NeuroCOVID consortium, as well as the translated versions adapted for use in Latin America. Global efforts are underway to further harmonize CDEs with other large consortia studying neurological and general aspects of COVID-19 infections. Ultimately, the GCS-NeuroCOVID consortium network provides a critical infrastructure to systematically capture data in current and future unanticipated disasters and disease outbreaks.