Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: One year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to summarize the frequency of neurologic manifestations reported in patients with COVID-19 and to investigate the association of these manifestations with disease severity and mortality. METHODS: We searched PubMed, Medline, Cochrane library, ClinicalTrials.gov, and EMBASE for studies from December 31, 2019, to December 15, 2020, enrolling consecutive patients with COVID-19 presenting with neurologic manifestations. Risk of bias was examined with the Joanna Briggs Institute scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% confidence intervals (CIs) were calculated for neurologic manifestations. Odds ratio (ORs) and 95% CIs were calculated to determine the association of neurologic manifestations with disease severity and mortality. Presence of heterogeneity was assessed with I 2, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2. RESULTS: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 patients with COVID-19, 89% of whom were hospitalized. Forty-one neurologic manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurologic symptoms included fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%), and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurologic diagnosis (pooled prevalence 2%). In patients with COVID-19 ≥60 years of age, the pooled prevalence of acute confusion/delirium was 34%, and the presence of any neurologic manifestations in this age group was associated with mortality (OR 1.80, 95% CI 1.11-2.91). DISCUSSION: Up to one-third of patients with COVID-19 analyzed in this review experienced at least 1 neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with nearly a doubling of mortality. Results must be interpreted with the limitations of observational studies and associated bias in mind. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020181867.

Delirium in Patients with SARS-CoV-2 Infection: A Multicenter Study.

OBJECTIVES: The aims of this study are to report the prevalence of delirium on admission to the unit in patients hospitalized with SARS-CoV-2 infection, to identify the factors associated with delirium, and to evaluate the association between delirium and in-hospital mortality. DESIGN: Multicenter observational cohort study. SETTINGS: Acute medical units in four Italian hospitals. PARTICIPANTS: A total of 516 patients (median age 78 years) admitted to the participating centers with SARS-CoV-2 infection from February 22 to May 17, 2020. MEASUREMENTS: Comprehensive medical assessment with detailed history, physical examinations, functional status, laboratory and imaging procedures. On admission, delirium was determined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria, 4AT, m-Richmond Agitation Sedation Scale, or clinical impression depending on the site. The primary outcomes were delirium rates and in-hospital mortality. RESULTS: Overall, 73 (14.1%, 95% confidence interval (CI) = 11.0-17.3%) patients presented delirium on admission. Factors significantly associated with delirium were dementia (odds ratio, OR = 4.66, 95% CI = 2.03-10.69), the number of chronic diseases (OR = 1.20, 95% CI = 1.03; 1.40), and chest X-ray or CT opacity (OR = 3.29, 95% CI = 1.12-9.64 and 3.35, 95% CI = 1.07-10.47, for multiple or bilateral opacities and single opacity vs no opacity, respectively). There were 148 (33.4%) in-hospital deaths in the no-delirium group and 43 (58.9%) in the delirium group (P-value assessed using the Gray test <.001). As assessed by a multivariable Cox model, patients with delirium on admission showed an almost twofold increased hazard ratio for in-hospital mortality with respect to patients without delirium (hazard ratio = 1.88, 95% CI = 1.25-2.83). CONCLUSION: Delirium is prevalent and associated with in-hospital mortality among older patients hospitalized with SARS-CoV-2 infection.

Clinical Features and Outcomes of Patients with Dementia Compared to an Aging Cohort Hospitalized During the Initial New York City COVID-19 Wave.

BACKGROUND: Patients with dementia are vulnerable during the coronavirus disease 2019 (COVID-19) pandemic, yet few studies describe their hospital course and outcomes. OBJECTIVE: To describe and compare the hospital course for COVID-19 patients with dementia to an aging cohort without dementia in a large New York City academic medical center. METHODS: This was a single-center retrospective cohort study describing all consecutive patients age 65 or older with confirmed COVID-19 who presented to the emergency department or were hospitalized at New York-Presbyterian/Columbia University Irving Medical Center between March 6 and April 7, 2020. RESULTS: A total of 531 patients were evaluated, including 116 (21.8%) with previously diagnosed dementia, and 415 without dementia. Patients with dementia had higher mortality (50.0%versus 35.4%, p = 0.006); despite similar comorbidities and complications, multivariate analysis indicated the association was dependent on age, sex, comorbidities, and code status. Patients with dementia more often presented with delirium (36.2%versus 11.6%, p < 0.001) but less often presented with multiple other COVID-19 symptoms, and these findings remained after adjusting for age and sex. CONCLUSION: Hospitalized COVID-19 patients with dementia had higher mortality, but dementia was not an independent risk factor for death. These patients were approximately 3 times more likely to present with delirium but less often manifested or communicated other common COVID-19 symptoms. For this high-risk population in a worsening pandemic, understanding the unique manifestations and course in dementia and aging populations may help guide earlier diagnosis and optimize medical management.

Functional and cognitive outcomes after COVID-19 delirium.

PURPOSE: To ascertain delirium prevalence and outcomes in COVID-19. METHODS: We conducted a point-prevalence study in a cohort of COVID-19 inpatients at University College Hospital. Delirium was defined by DSM-IV criteria. The primary outcome was all-cause mortality at 4 weeks; secondary outcomes were physical and cognitive function. RESULTS: In 71 patients (mean age 61, 75% men), 31 (42%) had delirium, of which only 12 (39%) had been recognised by the clinical team. At 4 weeks, 20 (28%) had died, 26 (36%) were interviewed by telephone and 21 (30%) remained as inpatients. Physical function was substantially worse in people after delirium - 50 out of 166 points (95% CI - 83 to - 17, p = 0.01). Mean cognitive scores at follow-up were similar and delirium was not associated with mortality in this sample. CONCLUSIONS: Our findings indicate that delirium is common, yet under-recognised. Delirium is associated with functional impairments in the medium term.