TY - JOUR
T1 - Frequency of neurologic manifestations in COVID-19
AU - Misra, Shubham
AU - Kolappa, Kavitha
AU - Prasad, Manya
AU - Radhakrishnan, Divya
AU - Thakur, Kiran T.
AU - Solomon, Tom
AU - Michael, Benedict Daniel
AU - Winkler, Andrea Sylvia
AU - Beghi, Ettore
AU - Guekht, Alla
AU - Pardo, Carlos A.
AU - Wood, Greta Karen
AU - Chou, Sherry Hsiang Yi
AU - Fink, Ericka L.
AU - Schmutzhard, Erich
AU - Kheradmand, Amir
AU - Hoo, Fan Kee
AU - Kumar, Amit
AU - Das, Animesh
AU - Srivastava, Achal K.
AU - Agarwal, Ayush
AU - Dua, Tarun
AU - Prasad, Kameshwar
N1 - Funding Information:
K. Prasad received funding from the WHO to support this systematic review and meta-analysis. S. Misra is a DST-INSPIRE Fellow supported by Department of Science and Technology, Government of India. S.H.-Y. Chou receives research funding from the NIH National Center for Advancing Translational Sciences through grant UL1 TR001857 (University of Pittsburgh/Chou), the National Institute of Neurological Disorders and Stroke (R21-NS113037), and the University of Pittsburgh School of Medicine Dean’s Faculty Advancement Award. E.L. Fink has a research grant from Neurocritical Care Society INCLINE grant, NIH (National Institute of Neurological Disorders and Stroke) R01 NS096714. C.A. Pardo is supported by NIH R01 NS110122 and Bart McLean Fund for Neuroimmunology Research. B.D. Michael is supported to conduct clinical COVID-19 neuroscience research by the UK Research and Innovation (UKRI)/Medical Research Council (MRC) (MR/V03605X/1); for additional neurological inflammation research due to SARS-CoV2 and associated viral infection, B.D.M. is also supported by grants from the MRC/UKRI (MR/V007181//1), MRC (MR/T028750/1), and Wellcome (ISSF201902/3). T. Solomon is supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (grants IS-HPU-1112-10117 and NIHR200907), NIHR Programme Grant for Applied Research (No. RP-PG-0108-10,048), NIHR Global Health Research Group on Brain Infections (No. 17/63/110), and the European Union's Horizon 2020 research and innovation program ZikaPLAN (Preparedness Latin America Network), grant agreement 734584.
Funding Information:
S.H.-Y. Chou serves as a member of Board of Directors for the Neurocritical Care Society. K.T. Thakur is being funded by Centers for Disease Control and Prevention on COVID-19 related research. T. Solomon was chair/co-chair of the UKRI/NIHR COVID-19 Rapid Response and Rolling Funding Initiatives and is an advisor to the UK COVID-19 Therapeutics Advisory Panel and a member of the MHRA COVID-19 Vaccines Benefit Risk Expert Working Group. E. Beghi reports grants from Italian Ministry of Health, grants from SOBI, personal fees from Arvelle Therapeutics, and grants from American ALS Association, outside the submitted work. S. Misra, K. Kolappa, M. Prasad, D. Radhakrishnan, B.D. Michael, A.S. Winkler, A. Guekht, C.A. Pardo, G.K. Wood, E.L. Fink, E. Schmutzhard, A. Kheradmand, F.K. Hoo, A. Kumar, A. Das, A.K. Srivastava, A. Agarwal, T. Dua, and K. Prasad report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
Copyright © 2021 American Academy of Neurology.
PY - 2021/12/7
Y1 - 2021/12/7
N2 - 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 I2, 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.
AB - 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 I2, 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.
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U2 - 10.1212/WNL.0000000000012930
DO - 10.1212/WNL.0000000000012930
M3 - Review article
C2 - 34635561
AN - SCOPUS:85119511689
SN - 0028-3878
VL - 97
SP - E2269-E2281
JO - Neurology
JF - Neurology
IS - 23
ER -