Shubham Misra1, Kavitha Kolappa1, Manya Prasad1, Divya Radhakrishnan1, Kiran T Thakur1, Tom Solomon1, Benedict Daniel Michael1, Andrea Sylvia Winkler1, Ettore Beghi1, Alla Guekht1, Carlos A Pardo1, Greta Karen Wood1, Sherry Hsiang-Yi Chou1, Ericka L Fink1, Erich Schmutzhard1, Amir Kheradmand1, Fan Kee Hoo1, Amit Kumar1, Animesh Das1, Achal K Srivastava1, Ayush Agarwal1, Tarun Dua1, Kameshwar Prasad2. 1. From the Department of Neurology (S.M., D.R., A.K., A.D., A.K.S., A.A.), All India Institute of Medical Sciences, New Delhi, India; Brain Health Unit (K.K., T.D.), World Health Organization, Geneva, Switzerland; Department of Clinical Research and Epidemiology (M.P.), Institute of Liver and Biliary Sciences, New Delhi, India; Columbia University Irving Medical Center-New York Presbyterian Hospital (K.T.T.), NY; Institute of Infection, Veterinary and Ecological Sciences (T.S., B.D.M., G.K.W.), University of Liverpool; Department of Neurology (T.S., B.D.M.), Walton Centre NHS Foundation Trust; NIHR Health Protection Research Unit for Emerging and Zoonotic Infection (B.D.M.), Liverpool, UK; Center for Global Health (A.S.W.), Department of Neurology, Technical University of Munich, Germany; Centre for Global Health (A.S.W.), Institute of Health and Society, University of Oslo, Norway; Istituto di Ricerche Farmacologiche Mario Negri IRCCS (E.B.), Milan, Italy; Moscow Research and Clinical Center for Neuropsychiatry and Pirogov Russian National Research Medical University (A.G.), Russia; Departments of Neurology and Pathology (C.A.P.), Johns Hopkins University School of Medicine, Baltimore, MD; University of Pittsburgh School of Medicine (S.H.-Y.C.); Department of Critical Care Medicine (E.L.F.), UPMC Children's Hospital of Pittsburgh, PA; Department of Neurology (E.S.), Medical University Innsbruck, Austria; Departments of Neurology and Otolaryngology-Head & Neck Surgery (A.K.), The Johns Hopkins Hospital, Baltimore, MD; Department of Neurology (F.K.H.), Faculty of Medicine and Health Sciences, University Putra Malaysia, Seri Kembangan; and Rajendra Institute of Medical Sciences (K.P.), Ranchi, Jharkhand, India. 2. From the Department of Neurology (S.M., D.R., A.K., A.D., A.K.S., A.A.), All India Institute of Medical Sciences, New Delhi, India; Brain Health Unit (K.K., T.D.), World Health Organization, Geneva, Switzerland; Department of Clinical Research and Epidemiology (M.P.), Institute of Liver and Biliary Sciences, New Delhi, India; Columbia University Irving Medical Center-New York Presbyterian Hospital (K.T.T.), NY; Institute of Infection, Veterinary and Ecological Sciences (T.S., B.D.M., G.K.W.), University of Liverpool; Department of Neurology (T.S., B.D.M.), Walton Centre NHS Foundation Trust; NIHR Health Protection Research Unit for Emerging and Zoonotic Infection (B.D.M.), Liverpool, UK; Center for Global Health (A.S.W.), Department of Neurology, Technical University of Munich, Germany; Centre for Global Health (A.S.W.), Institute of Health and Society, University of Oslo, Norway; Istituto di Ricerche Farmacologiche Mario Negri IRCCS (E.B.), Milan, Italy; Moscow Research and Clinical Center for Neuropsychiatry and Pirogov Russian National Research Medical University (A.G.), Russia; Departments of Neurology and Pathology (C.A.P.), Johns Hopkins University School of Medicine, Baltimore, MD; University of Pittsburgh School of Medicine (S.H.-Y.C.); Department of Critical Care Medicine (E.L.F.), UPMC Children's Hospital of Pittsburgh, PA; Department of Neurology (E.S.), Medical University Innsbruck, Austria; Departments of Neurology and Otolaryngology-Head & Neck Surgery (A.K.), The Johns Hopkins Hospital, Baltimore, MD; Department of Neurology (F.K.H.), Faculty of Medicine and Health Sciences, University Putra Malaysia, Seri Kembangan; and Rajendra Institute of Medical Sciences (K.P.), Ranchi, Jharkhand, India. drkameshwarprasad@gmail.com.
Abstract
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.
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.
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