Background: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. Methods: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). Results: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: “headache” (0.12; 0.10–0.14; I2 = 77%), “dizziness” (0.08; 0.05–0.12; I2 = 82%), “headache and dizziness” (0.09; 0.06–0.13; I2 = 0%), “nausea” (0.07; 0.04–0.11; I2 = 79%), “vomiting” (0.05; 0.03–0.08; I2 = 74%), “nausea and vomiting” (0.06; 0.03–0.11; I2 = 83%), “confusion” (0.05; 0.02–0.14; I2 = 86%), and “myalgia” (0.21; 0.18–0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain–Barré syndrome (n = 1), and Miller–Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). Conclusion: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.
Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132–2.435) and by 1.352 (95% CI 1.042–1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346–2.722), by 1.614 (95% CI 1.260–2.068), and by 1.234 (95% CI 1.089–1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457–2.673) and by 1.831 (95% CI 1.506–2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772–1.179), longer ICU stay (aOR 0.983, 95% CI 0.772–1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947–1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944.
IntroductionThe SARS-CoV-2, virus that caused the COVID-19 global pandemic, possesses a neuroinvasive potential. Patients with COVID-19 infection present with neurological signs and symptoms aside from the usual respiratory affectation. Moreover, COVID-19 is associated with several neurological diseases and complications, which may eventually affect clinical outcomes.ObjectivesThe Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA) study investigators will conduct a nationwide, multicentre study involving 37 institutions that aims to determine the neurological manifestations and factors associated with clinical outcomes in COVID-19 infection.Methodology and analysisThis is a retrospective cohort study (comparative between patients with and without neurological manifestations) via medical chart review involving adult patients with COVID-19 infection. Sample size was determined at 1342 patients. Demographic, clinical and neurological profiles will be obtained and summarised using descriptive statistics. Student’s t-test for two independent samples and χ2 test will be used to determine differences between distributions. HRs and 95% CI will be used as an outcome measure. Kaplan-Meier curves will be constructed to plot the time to onset of mortality (survival), respiratory failure, intensive care unit (ICU) admission, duration of ventilator dependence, length of ICU stay and length of hospital stay. The log-rank test will be employed to compare the Kaplan-Meier curves. Stratified analysis will be performed to identify confounders and effects modifiers. To compute for adjusted HR with 95% CI, crude HR of outcomes will be adjusted according to the prespecified possible confounders. Cox proportional regression models will be used to determine significant factors of outcomes. Testing for goodness of fit will also be done using Hosmer-Lemeshow test. Subgroup analysis will be performed for proven prespecified effect modifiers. The effects of missing data and outliers will also be evaluated in this study.Ethics and disseminationThis protocol was approved by the Single Joint Research Ethics Board of the Philippine Department of Health (SJREB-2020–24) and the institutional review board of the different study sites. The dissemination of results will be conducted through scientific/medical conferences and through journal publication. The lay versions of the results may be provided on request.Trial registration numberNCT04386083.
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