Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

Jonathan P. Rogers; Cameron J. Watson; James Badenoch; Benjamin Cross; Matthew Butler; Jia Song; Danish Hafeez; Hamilton Morrin; Emma Rachel Rengasamy; Lucretia Thomas; Silviya Ralovska; Abigail Smakowski; Ritika Dilip Sundaram; Camille Kaitlyn Hunt; Mao Fong Lim; Daruj Aniwattanapong; Vanshika Singh; Zain Hussain; Stuti Chakraborty; Ella Burchill; Katrin Jansen; Heinz Holling; Dean Walton; Thomas A. Pollak; Mark Ellul; Ivan Koychev; Tom Solomon; Benedict Daniel Michael; Timothy R. Nicholson; Alasdair G. Rooney

doi:10.1136/jnnp-2021-326405

Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

Jonathan P. Rogers^*, Cameron J. Watson, James Badenoch, Benjamin Cross, Matthew Butler, Jia Song, Danish Hafeez, Hamilton Morrin, Emma Rachel Rengasamy, Lucretia Thomas, Silviya Ralovska, Abigail Smakowski, Ritika Dilip Sundaram, Camille Kaitlyn Hunt, Mao Fong Lim, Daruj Aniwattanapong, Vanshika Singh, Zain Hussain, Stuti Chakraborty, Ella BurchillKatrin Jansen, Heinz Holling, Dean Walton, Thomas A. Pollak, Mark Ellul, Ivan Koychev, Tom Solomon, Benedict Daniel Michael, Timothy R. Nicholson, Alasdair G. Rooney

^*Corresponding author for this work

Psychosis Studies

Research output: Contribution to journal › Review article › peer-review

92 Citations (Scopus)

Abstract

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations. We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence. 13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high. Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

Original language	English
Article number	326405
Pages (from-to)	932-941
Number of pages	10
Journal	Journal of Neurology, Neurosurgery and Psychiatry
Volume	92
Issue number	9
DOIs	https://doi.org/10.1136/jnnp-2021-326405
Publication status	Published - 1 Sept 2021

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10.1136/jnnp-2021-326405

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Rogers, J. P., Watson, C. J., Badenoch, J., Cross, B., Butler, M., Song, J., Hafeez, D., Morrin, H., Rengasamy, E. R., Thomas, L., Ralovska, S., Smakowski, A., Sundaram, R. D., Hunt, C. K., Lim, M. F., Aniwattanapong, D., Singh, V., Hussain, Z., Chakraborty, S., ... Rooney, A. G. (2021). Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives. Journal of Neurology, Neurosurgery and Psychiatry, 92(9), 932-941. Article 326405. https://doi.org/10.1136/jnnp-2021-326405

@article{aaed13e5f4bd4d579d2fba5670e1a214,

title = "Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives",

abstract = "There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations. We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence. 13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high. Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.",

author = "Rogers, {Jonathan P.} and Watson, {Cameron J.} and James Badenoch and Benjamin Cross and Matthew Butler and Jia Song and Danish Hafeez and Hamilton Morrin and Rengasamy, {Emma Rachel} and Lucretia Thomas and Silviya Ralovska and Abigail Smakowski and Sundaram, {Ritika Dilip} and Hunt, {Camille Kaitlyn} and Lim, {Mao Fong} and Daruj Aniwattanapong and Vanshika Singh and Zain Hussain and Stuti Chakraborty and Ella Burchill and Katrin Jansen and Heinz Holling and Dean Walton and Pollak, {Thomas A.} and Mark Ellul and Ivan Koychev and Tom Solomon and Michael, {Benedict Daniel} and Nicholson, {Timothy R.} and Rooney, {Alasdair G.}",

note = "Funding Information: Contributors TRN and AR conceived the study. AR and JPR led and coordinated the study. MB compared the work with other systematic reviews. CW, BC, MB, JS, DH, ERR, LT, AR, MFL and JB screened studies for eligibility. AR, JPR, JS and MB consulted on study inclusion. CW, BC, DH, HM, ERR, LT, SR, RDS and JB extracted the data. JB, MB, JS, DH, HM, ERR, LT, SR, AS, RDS, CKH, MFL, DA, AR and BC checked data extraction. AR conducted OCEBM ratings. JPR calculated descriptive statistics. CW and KJ conducted the meta-analysis, supported by HH. CW and DH created figures. JPR, BC, MB, JS, DH, HM, LT, SR, AS, RDS, CKH, MFL, VS, ZH, SC, EB, DW, TAP, ME, IK, TRN, AR and JB conducted quality assessment. JPR and AS supervised and arbitrated quality assessment. JB made the PRISMA flow chart. JPR, MB and JB sorted references. JB checked adherence to PRISMA guidelines. AR, JPR, JB, ERR, VS and MB drafted the manuscript. JPR, MB, JS and JB checked the completed manuscript. ERR and ZH created tables. MFL sorted funding statements. JPR and EB formatted the manuscript. DW, ME, IK, TS, BDM, TRN, AR and TAP provided senior review of the manuscript. JPR and AR are responsible for the overall content of the study. Funding Information: Funding JPR is supported by a Wellcome Trust Clinical Training Fellowship (102186/B/13/Z). MB is a National Institute of Health Research (NIHR) Academic Clinical Fellow (ACF-2019-17-008). HH is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) (HO1286/16-1). TAP is supported by an NIHR Clinical Lectureship (no award/grant number). ME is supported by the Association of British Neurologists through a Clinical Research Training Fellowship (no award/grant number). ME and TS are supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR200907). IK is supported by the Medical Research Council (Dementias Platform UK Grant MR/L023784/2) and the Oxford Health Biomedical Research Centre (no award/ grant number). DA is supported by the Faculty of Medicine, Chulalongkorn University, Thailand (no award/grant number). AR is supported by the Royal College of Physicians of Edinburgh, John, Margaret, Alfred and Stewart Sim Fellowship 2018–2020 (no award/grant number). BDM is supported by the UKRI/MRC COVID-CNS grant (MR/V03605X/1), the MRC-CSF (MR/V007181/1), and the MRC/AMED grant (MR/T028750/1). Funding Information: JPR is supported by a Wellcome Trust Clinical Training Fellowship (102186/B/13/Z). MB is a National Institute of Health Research (NIHR) Academic Clinical Fellow (ACF-2019-17-008). HH is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) (HO1286/16-1). TAP is supported by an NIHR Clinical Lectureship (no award/grant number). ME is supported by the Association of British Neurologists through a Clinical Research Training Fellowship (no award/grant number). ME and TS are supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR200907). IK is supported by the Medical Research Council (Dementias Platform UK Grant MR/L023784/2) and the Oxford Health Biomedical Research Centre (no award/grant number). DA is supported by the Faculty of Medicine, Chulalongkorn University, Thailand (no award/grant number). AR is supported by the Royal College of Physicians of Edinburgh, John, Margaret, Alfred and Stewart Sim Fellowship 2018?2020 (no award/grant number). BDM is supported by the UKRI/MRC COVID-CNS grant (MR/V03605X/1), the MRC-CSF (MR/V007181/1), and the MRC/AMED grant (MR/T028750/1). Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = sep,

day = "1",

doi = "10.1136/jnnp-2021-326405",

language = "English",

volume = "92",

pages = "932--941",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group Ltd",

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Rogers, JP, Watson, CJ, Badenoch, J, Cross, B, Butler, M, Song, J, Hafeez, D, Morrin, H, Rengasamy, ER, Thomas, L, Ralovska, S, Smakowski, A, Sundaram, RD, Hunt, CK, Lim, MF, Aniwattanapong, D, Singh, V, Hussain, Z, Chakraborty, S, Burchill, E, Jansen, K, Holling, H, Walton, D, Pollak, TA, Ellul, M, Koychev, I, Solomon, T, Michael, BD, Nicholson, TR & Rooney, AG 2021, 'Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives', Journal of Neurology, Neurosurgery and Psychiatry, vol. 92, no. 9, 326405, pp. 932-941. https://doi.org/10.1136/jnnp-2021-326405

Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives. / Rogers, Jonathan P.; Watson, Cameron J.; Badenoch, James et al.
In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 92, No. 9, 326405, 01.09.2021, p. 932-941.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Neurology and neuropsychiatry of COVID-19

T2 - A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

AU - Rogers, Jonathan P.

AU - Watson, Cameron J.

AU - Badenoch, James

AU - Cross, Benjamin

AU - Butler, Matthew

AU - Song, Jia

AU - Hafeez, Danish

AU - Morrin, Hamilton

AU - Rengasamy, Emma Rachel

AU - Thomas, Lucretia

AU - Ralovska, Silviya

AU - Smakowski, Abigail

AU - Sundaram, Ritika Dilip

AU - Hunt, Camille Kaitlyn

AU - Lim, Mao Fong

AU - Aniwattanapong, Daruj

AU - Singh, Vanshika

AU - Hussain, Zain

AU - Chakraborty, Stuti

AU - Burchill, Ella

AU - Jansen, Katrin

AU - Holling, Heinz

AU - Walton, Dean

AU - Pollak, Thomas A.

AU - Ellul, Mark

AU - Koychev, Ivan

AU - Solomon, Tom

AU - Michael, Benedict Daniel

AU - Nicholson, Timothy R.

AU - Rooney, Alasdair G.

N1 - Funding Information: Contributors TRN and AR conceived the study. AR and JPR led and coordinated the study. MB compared the work with other systematic reviews. CW, BC, MB, JS, DH, ERR, LT, AR, MFL and JB screened studies for eligibility. AR, JPR, JS and MB consulted on study inclusion. CW, BC, DH, HM, ERR, LT, SR, RDS and JB extracted the data. JB, MB, JS, DH, HM, ERR, LT, SR, AS, RDS, CKH, MFL, DA, AR and BC checked data extraction. AR conducted OCEBM ratings. JPR calculated descriptive statistics. CW and KJ conducted the meta-analysis, supported by HH. CW and DH created figures. JPR, BC, MB, JS, DH, HM, LT, SR, AS, RDS, CKH, MFL, VS, ZH, SC, EB, DW, TAP, ME, IK, TRN, AR and JB conducted quality assessment. JPR and AS supervised and arbitrated quality assessment. JB made the PRISMA flow chart. JPR, MB and JB sorted references. JB checked adherence to PRISMA guidelines. AR, JPR, JB, ERR, VS and MB drafted the manuscript. JPR, MB, JS and JB checked the completed manuscript. ERR and ZH created tables. MFL sorted funding statements. JPR and EB formatted the manuscript. DW, ME, IK, TS, BDM, TRN, AR and TAP provided senior review of the manuscript. JPR and AR are responsible for the overall content of the study. Funding Information: Funding JPR is supported by a Wellcome Trust Clinical Training Fellowship (102186/B/13/Z). MB is a National Institute of Health Research (NIHR) Academic Clinical Fellow (ACF-2019-17-008). HH is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) (HO1286/16-1). TAP is supported by an NIHR Clinical Lectureship (no award/grant number). ME is supported by the Association of British Neurologists through a Clinical Research Training Fellowship (no award/grant number). ME and TS are supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR200907). IK is supported by the Medical Research Council (Dementias Platform UK Grant MR/L023784/2) and the Oxford Health Biomedical Research Centre (no award/ grant number). DA is supported by the Faculty of Medicine, Chulalongkorn University, Thailand (no award/grant number). AR is supported by the Royal College of Physicians of Edinburgh, John, Margaret, Alfred and Stewart Sim Fellowship 2018–2020 (no award/grant number). BDM is supported by the UKRI/MRC COVID-CNS grant (MR/V03605X/1), the MRC-CSF (MR/V007181/1), and the MRC/AMED grant (MR/T028750/1). Funding Information: JPR is supported by a Wellcome Trust Clinical Training Fellowship (102186/B/13/Z). MB is a National Institute of Health Research (NIHR) Academic Clinical Fellow (ACF-2019-17-008). HH is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) (HO1286/16-1). TAP is supported by an NIHR Clinical Lectureship (no award/grant number). ME is supported by the Association of British Neurologists through a Clinical Research Training Fellowship (no award/grant number). ME and TS are supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England, in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR200907). IK is supported by the Medical Research Council (Dementias Platform UK Grant MR/L023784/2) and the Oxford Health Biomedical Research Centre (no award/grant number). DA is supported by the Faculty of Medicine, Chulalongkorn University, Thailand (no award/grant number). AR is supported by the Royal College of Physicians of Edinburgh, John, Margaret, Alfred and Stewart Sim Fellowship 2018?2020 (no award/grant number). BDM is supported by the UKRI/MRC COVID-CNS grant (MR/V03605X/1), the MRC-CSF (MR/V007181/1), and the MRC/AMED grant (MR/T028750/1). Publisher Copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations. We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence. 13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high. Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

AB - There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations. We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence. 13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high. Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

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U2 - 10.1136/jnnp-2021-326405

DO - 10.1136/jnnp-2021-326405

M3 - Review article

C2 - 34083395

AN - SCOPUS:85107855740

SN - 0022-3050

VL - 92

SP - 932

EP - 941

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 9

M1 - 326405

ER -

Neurology and neuropsychiatry of COVID-19: A systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

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