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Cited by 1,246Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesInfectious Encephalopathies and Encephalitis

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Open access
Varatharaj, Aravinthan, Thomas, Naomi, Ellul, Mark A, Davies, Nicholas W S, Pollak, Thomas A, Tenorio, Elizabeth L, Sultan, Mustafa, Easton, Ava +107 more·2020·The Lancet Psychiatry
DOI 10.1016/s2215-0366(20)30287-xPMC PMC7316461
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Abstract

Background Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.Methods During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.Findings The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23-94; IQR 58-79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.Interpretation To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.Funding None.

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Crossref · 10.1016/s2215-0366(20)30287-x

Cites

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Claims the paper makes

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  • Findingown data

    Among the 125 patients with complete data, 77 (62%) presented with a cerebrovascular event.

    “77 (62%) of 125 patients presented with a cerebrovascular event”
    Quote in the paperSubstantial claim
  • Findingown data

    One (1%) of the 77 patients with cerebrovascular events had CNS vasculitis.

    “one (1%) CNS vasculitis”
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  • Findingown data

    Among the 77 patients with cerebrovascular events, 57 (74%) had an ischaemic stroke.

    “of whom 57 (74%) had an ischaemic stroke”
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  • Findingown data

    Of the 23 patients with neuropsychiatric disorders, ten (43%) had new-onset psychosis.

    “Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis”
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  • Findingown data

    Among the 39 patients with altered mental status, the remaining 23 (59%) fulfilled clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist.

    “The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist”
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    Findingown data

    The median age of 71 years was similar to national data, although for some centiles an older population could be overrepresented in the study cohort.

    “Overall, the median age of 71 years (range 23–94; IQR 58–79) was similar to national data collected through UK Government public health bodies over the same time period, although for some centiles an older population could be overrepresented within the study cohort”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The UK Government public health data used for comparison accurately reflect the overall COVID-19 case distribution.

  • May combine two claims.

    Findingown data

    Among 74 patients with cerebrovascular events and age data, 13 (18%) were younger than 60 years and 61 (82%) were older than 60 years.

    “13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years”
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    Findingown data

    Of the 125 patients with complete notification data, 114 (92%) met criteria for confirmed SARS-CoV-2 infection, five (4%) for probable infection, and five (4%) for possible infection.

    “114 (92%) of 125 patients with complete notification data met the criteria for confirmed SARS-CoV-2 infection, five (4%) met the criteria for probable SARS-CoV-2 infection, and five (4%) met the criteria for possible SARS-CoV-2 infection.”
    Quote in the paperNot a substantial claim

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    Findingown data

    The median age of notified patients was 71 years, with a range of 23-94 and an interquartile range of 58-79.

    “Median patient age was 71 years (range 23–94; IQR 58–79).”
    Quote in the paperNot a substantial claim

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    Findingown data

    Dates of admission or initial clinical assessment were available for 112 (90%) of 125 patients and correlated with national case identification data over the same period, reflecting the exponential phase of infection.

    “Dates of admission or initial clinical assessment were available for 112 (90%) of 125 patients and correlated with the national case identification data of all laboratory-confirmed patients with COVID-19 reported by government public health bodies over the same time period, reflecting the exponential phase of infection”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The UK Government public health data used for comparison accurately reflect the overall COVID-19 case distribution.

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    Findingown data

    Of the 23 patients with neuropsychiatric disorders, seven (30%) had another psychiatric disorder, including one case of catatonia and one case of mania.

    “and seven (30%) had an other psychiatric disorder, including one case of catatonia and one case of mania.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The RCPsych web portal was launched 18 days later than the other portals, yet a large number of psychiatric or neuropsychiatric notifications were observed.

    “the RCPsych web portal was launched 18 days later than the other neurological, stroke, and intensive care unit or more general portals, yet we observed a large number of psychiatric or neuropsychiatric notifications.”
    Quote in the paperSubstantial claim

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    Findingown data

    Of 153 cases, 75 (49%) were notified through the BASP portal, 53 (35%) through ABN or CoroNerve.com, and 25 (16%) through the RCPsych portal.

    “Overall, 75 (49%) of 153 cases were notified through the BASP portal, 53 (35%) through ABN or CoroNerve.com, and 25 (16%) through the RCPsych portal.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Data on reporting physician specialty were available for 150 patients: 61 (41%) were stroke physicians, 39 (26%) neurologists, 26 (17%) psychiatrists or neuropsychiatrists, 23 (15%) acute medicine or other physicians, and one (1%) a general practitioner.

    “Data on reporting physician specialty were available for 150 patients: 61 (41%) were stroke physicians, 39 (26%) were neurologists, 26 (17%) were psychiatrists or neuropsychiatrists, 23 (15%) were acute medicine or other physicians, and one (1%) was a general practitioner.”
    Quote in the paperNot a substantial claim

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    Findingown data

    Among 37 patients with altered mental status and age data, 18 (49%) were younger than 60 years and 19 (51%) were older than 60 years.

    “18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Cases were geographically dispersed across the UK, as were overall laboratory-confirmed COVID-19 cases reported by government public health bodies during the same period.

    “Patients were geographically dispersed across the UK, as were overall laboratory-confirmed cases of patients with COVID-19 reported by government public health bodies during the same time period”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The UK Government public health data used for comparison accurately reflect the overall COVID-19 case distribution.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of 152 patients with admitting unit data, 26 (17%) were from tertiary care hospitals, 125 (82%) from secondary care hospitals, and one (1%) from primary care.

    “26 (17%) of 152 patients were from tertiary care hospitals, 125 (82%) were from secondary care hospitals, and one (1%) was from primary care.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Cases were reported retrospectively for 24 (16%) of 153 patients, and the remainder were reported prospectively.

    “Cases were reported retrospectively for 24 (16%) of 153 patients and the remainder were reported prospectively.”
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    Study design and conductnone given

    The approach to case ascertainment has potential for reporting bias and requires validation through detailed prospective clinicoepidemiological data collection.

    “Our approach to case ascertainment has the potential for reporting bias and requires validation through detailed prospective clinicoepidemiological data collection.”
    Quote in the paperSubstantial claim

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    Interpretationown data

    Altered mental status comprised encephalopathy or encephalitis and primary psychiatric diagnoses.

    “comprising encephalopathy or encephalitis and primary psychiatric diagnoses”
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    Premisecitation

    Cerebrovascular events in patients with COVID-19 have been well described elsewhere.

    “Cerebrovascular events in patients with COVID-19, which have been well described elsewhere,1, 9 were also identified as a major group within our cohort.”
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    Premisecitation

    Existing studies identifying patients with neurological complications across centres have largely been limited to two or three hospitals and restricted by geography and specialty, so they did not assess complications across the clinical spectrum.

    “However, these studies have largely been limited to two or three hospitals and are restricted by both geography and specialty, therefore not assessing the neurological and neuropsychiatric complications of COVID-19 across the clinical spectrum of neurology, stroke or acute medicine, psychiatry, and intensive care.”
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    Study design and conductnone given

    The study included a priori considerations to determine the strength of evidence for SARS-CoV-2 infection, and data collection was informed by clear clinical case definitions.

    “the present study included a priori considerations to determine the strength of the evidence for SARS-CoV-2 infection, and data collection was informed by clear clinical case definitions”
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    Premisecitation

    There is a potential biological rationale for a vasculopathy, with reports of SARS-CoV-2 endothelitis outside the cerebral vasculature and cerebrovascular events, in addition to coagulopathy and conventional stroke risk during sepsis.

    “there is a potential biological rationale for a vasculopathy, with a report of SARS-CoV-2 endothelitis in organs outside the cerebral vasculature22 and cerebrovascular events,23 in addition to coagulopathy, along with conventional stroke risk during sepsis.9, 24, 25”
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  • The paper relies on this without support.

    The UK Government public health data used for comparison accurately reflect the overall COVID-19 case distribution.

    “Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.”
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Authors
Varatharaj, A., Thomas, N., Ellul, M. A., Davies, N. W. S., Pollak, T. A., Tenorio, E. L., Sultan, M., Easton, A., Breen, G., Zandi, M., Coles, J. P., Manji, H., Al-Shahi Salman, R., Menon, D. K., Nicholson, T. R., Benjamin, L. A., Carson, A., Smith, C., Turner, M. R., Solomon, T., Kneen, R., Pett, S. L., Galea, I., Thomas, R. H., Michael, B. D., Allen, C., Archibald, N., Arkell, J., Arthur-Farraj, P., Baker, M., Ball, H., Bradley-Barker, V., Brown, Z., Bruno, S., Carey, L., Carswell, C., Chakrabarti, A., Choulerton, J., Daher, M., Davies, R., Di Marco Barros, R., Dima, S., Dunley, R., Dutta, D., Ellis, R., Everitt, A., Fady, J., Fearon, P., Fisniku, L., Gbinigie, I., Gemski, A., Gillies, E., Gkrania-Klotsas, E., Grigg, J., Hamdalla, H., Hubbett, J., Hunter, N., Huys, A.-C., Ihmoda, I., Ispoglou, S., Jha, A., Joussi, R., Kalladka, D., Khalifeh, H., Kooij, S., Kumar, G., Kyaw, S., Li, L., Littleton, E., Macleod, M., Macleod, M. J., Madigan, B., Mahadasa, V., Manoharan, M., Marigold, R., Marks, I., Matthews, P., Mccormick, M., Mcinnes, C., Metastasio, A., Milburn-McNulty, P., Mitchell, C., Mitchell, D., Morgans, C., Morris, H., Morrow, J., Mubarak Mohamed, A., Mulvenna, P., Murphy, L., Namushi, R., Newman, E., Phillips, W., Pinto, A., Price, D. A., Proschel, H., Quinn, T., Ramsey, D., Roffe, C., Ross Russell, A., Samarasekera, N., Sawcer, S., Sayed, W., Sekaran, L., Serra-Mestres, J., Snowdon, V., Strike, G., Sun, J., Tang, C., Vrana, M., Wade, R., Wharton, C., Wiblin, L., Boubriak, I., Herman, K., & Plant, G.
Affiliations
  • University Hospital Southampton NHS Foundation Trust (GB)
  • Wellcome Centre for Mitochondrial Research (GB)
  • University of Liverpool (GB)
  • Chelsea and Westminster Hospital NHS Foundation Trust (GB)
  • King's College London (GB)
  • University of Utah (US)
  • Newcastle University (GB)
  • UCL Queen Square Institute of Neurology (GB)
  • University of Cambridge (GB)
  • University of Edinburgh (GB)
  • Manchester Academic Health Science Centre (GB)
  • University of Oxford (GB)
  • MRC Clinical Trials Unit at UCL (GB)
  • Royal Victoria Infirmary (GB)
Corresponding author
Michael, Benedict D
ORCID
Venue
The Lancet Psychiatry
Publisher
Elsevier BV
Published
2020-10
Volume
7
Issue
10
Pages
875-882
ISSN
2215-0366 (ISSN-L)
DOI
10.1016/s2215-0366(20)30287-x
PMC
PMC7316461
OpenAlex
W3037535840
Cited by
1,246
References
24
Citations by year
2026: 17 · 2025: 51 · 2024: 89 · 2023: 141 · 2022: 287 · 2021: 466 · 2020: 195
FWCI
117.99
Type
journal article
Language
en
Update notices
erratum (2020-10-01)
Open access
Licence
Locations
  • The Lancet Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • GlaxoSmithKline
  • Intensive Care Society
  • National Institute for Health Research
  • Association of British Paediatric Nurses
  • Fondation Leducq
  • Stroke Association
  • Royal College of Psychiatrists
  • UCLH Biomedical Research Centre
  • Motor Neurone Disease Association
  • Wellcome Trust
  • European Society of Intensive Care Medicine
  • Academy of Medical Sciences
  • European Commission (734584)
  • Medical Research Council
  • Association for Cardiothoracic Anaesthesia and Critical Care
Topics
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
Keywords
COVID-19 pandemic, neurological complications, neuropsychiatric complications, cerebrovascular events, stroke, altered mental status, peripheral neuropathy, case surveillance, clinical syndromes
MeSH terms
Betacoronavirus, COVID-19, SARS-CoV-2, Adult, Age Factors, Aged, Aged, 80 and over, Mental Disorders, Cerebrovascular Disorders, Female, United Kingdom, Humans, Male, Middle Aged, Pneumonia, Viral, Retrospective Studies, Sex Factors, Coronavirus Infections, Young Adult, Pandemics

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