Multicenter Study

. 2025 Jan 27;15(1):3443.

doi: 10.1038/s41598-024-80833-0.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study

Rajish S K Shil^{1

2

3

4}, Adam Seed⁵, Nkongho Egbe Franklyn⁶, Brendan F Sargent^{6

7

8}, Greta K Wood^{6

5}, Yun Huang^{6

9

10}, Katherine C Dodd¹¹, James B Lilleker^{11

12}, Thomas A Pollak^{13

14}, Sylviane Defres^{6

9}, Thomas M Jenkins^{15

16

17

18}, Nicholas W S Davies¹⁹, David A Cousins²⁰, Michael S Zandi²¹, Thomas A Jackson²², Laura A Benjamin^{10

23}, Ava Easton^{6

24}, Tom Solomon^{6

9

10

25}, John R Bradley²⁶, Patrick F Chinnery^{27

28}, Craig J Smith^{11

29

30}, Timothy R Nicholson^{13

14}, Alan Carson³¹, Rhys H Thomas^{32

33

34}, Mark Alexander Ellul^{6

9

10}, Nicholas W Wood³⁵, Gerome Breen⁶, Benedict Daniel Michael^{36

37

38

39}; COVID-CNS Study Group

Collaborators, Affiliations

Collaborators

COVID-CNS Study Group:
John P Aggleton, Ali M Aggleton, Ammar Al-Chalabi, Christopher M Allen, Jay Amin, Cherie Armour, Mark R Baker, Suzanne Barret, Neil Basu, Rahul Batra, Alex Berry, Laura Benjamin, Richard A I Bethlehem, Bethan Blackledge, Sarah A Boardman, John Bradley, David P Breen, Gerome Breen, Judith Breuer, Matthew Broome, Ed Bullmore, Matthew Butler, Alan Carson, Hannah Castell, Jonathan Cavanagh, Patrick Chinnery, David Christmas, David M Christmas, Jonathan R I Coleman, Alaistair Coles, Ceryce Collie, Nadine Cossette, David Cousins, Colm Cunningham, Alastair Darby, Anthony S David, Nicholas Davies, Sylviane Defres, Katherine C Dodd, Alex Dregan, Eugene Duff, Cordelia Dunai, Ava Easton, Franklyn N Egbe, Mark A Ellul, Nikos Evangelou, Bethany Facer, Peter M Fernandes, Richard Francis, Ian Galea, Afagh Garjani, Lily George, Valentina Giunchiglia, Kiran Glen, Rebecca Gregory, Michael Griffiths, Victoria Grimbly, Alexander Grundmann, Savini Gunatilake, Shahd H M Hamid, Adam Hampshire, Marc Hardwick, Jade D Harris, Ewan Harrison, NeiL A Harrison, Paul J Harrison, Monika Hartmann, Peter J Hellyer, Claire Hetherington, Orla Hilton, Julian Hiscox, Eva Maria Hodel, Angela E Holland, Matthew Hotopf, Yun Huang, Stella Hughes, Masud Husain, Sarosh Irani, Thomas A Jackson, Thomas M Jackson, Peter Jezzard, Johan Kallberg Zvrskovec, Gursharan Kalsi, Simon Keller, Nathalie Kingston, Sandar Kyaw, E Charles Leek, Gabriella Lewis, James B Lilleker, Michael P P Lunn, Claire L MacIver, Daniel Madarshahian, Parisa Mansoori, Naomi Martin, Gavin McDonnell, Emily McGlinchey, Stephen McKeever, Ryan McIlwaine, Andrew M McIntosh, David K Menon, Benedict D Michael, Karla L Miller, Dina Monssen, Christopher M Morris, Ciaran Mulholland, Akshay Nair, Edward Needham, Virginia Newcombe, Nathalie Nicholas, Timothy R Nicholson, Ronan O'Malley, Obioma Orazulume, Marlies Ostermann, Stella-Maria Paddick, Alish Palmos, Arvind Patel, Sharon Peacock, Sophie L Pendered, Sarah L Pett, Thomas A Pollak, Angela Roberts, Henry C Rogers, Silvia Rota, Rustam Al-Shahi Salman, Merna Samuel, Brendan F Sargent, Stephen J Sawcer, Adam W Seed, Scott Semple, Pamela J Shaw, Rajish S K Shil, Adam Sieradzki, Bhagteshwar Singh, Craig J Smith, Jacqueline Smith, Stephen M Smith, Tom Solomon, Leonie Taams, Arina Tamborska, John-Paul Taylor, Kukatharmini Tharmaratnam, Rhys H Thomas, Emma Thomson, William Trender, Zain-Ul-Abideen Ahmad, Jonathan Underwood, Rachel Upthegrove, Tonny Veenith, Annalena Venneri, Angela Vincent, Daniel J van Wamelen, Guy Williams, Steven Williams, Sui Hsien Wong, Greta K Wood, Nicholas Wood, Michael S Zandi, Fernando Zelaya, Kathleen E Stirrups, Laura Cocking, Rose Eichenberger, Debbie Clapham, Hannah Stark

Affiliations

¹ Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. rajishsk@liverpool.ac.uk.
² Department of Neurology, Walton Centre of Neurosurgery and Neurology, Liverpool, UK. rajishsk@liverpool.ac.uk.
³ Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. rajishsk@liverpool.ac.uk.
⁴ Institute of Infection, Veterinary and Ecological Sciences, National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. rajishsk@liverpool.ac.uk.
⁵ Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
⁶ Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
⁷ Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
⁸ Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.
⁹ Department of Neurology, Walton Centre of Neurosurgery and Neurology, Liverpool, UK.
¹⁰ Institute of Infection, Veterinary and Ecological Sciences, National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.
¹¹ Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, M6 8HD, UK.
¹² Division of Musculoskeletal & Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, UK.
¹³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 4AF, UK.
¹⁴ South London and Maudsley NHS Foundation Trust, London, UK.
¹⁵ Curtin University, Kent Street, Bentley, Perth, WA, 6102, Australia.
¹⁶ Sheffield Institute for Translational Neuroscience, 385a Glossop Road, Sheffield, UK.
¹⁷ Department of Neurology, Joondalup Healthcare Campus, 60 Shenton Avenue, JoondalupPerth, WA, 6027, Australia.
¹⁸ Midland St John of God Hospital, 1 Clayton Street, Midland, Perth, WA, 6056, Australia.
¹⁹ Department of Neurology, Charing Cross Hospital, London, UK.
²⁰ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne, NE4 5PL, UK.
²¹ UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
²² MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
²³ Laboratory of Molecular and Cell Biology, University College London, Gower St, King's Cross, London, WC1E 6BT, UK.
²⁴ Encephalitis International, Malton, UK.
²⁵ The Pandemic Institute, The Spine, Liverpool, L7 3FA, UK.
²⁶ NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge, UK.
²⁷ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
²⁸ MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
²⁹ Geoffrey Jefferson Brain Research Centre, Clinical Sciences Building, Northern Care Alliance NHS Foundation Trust, Salford, M6 8FJ, UK.
³⁰ Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, UK.
³¹ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.
³² Translational and Clinical Research, Newcastle University, Newcastle, NE1 7RU, UK.
³³ Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle, NE2 4HH, UK.
³⁴ Department of Neurology, Royal Victoria Infirmary, Newcastle, NE1 4LP, UK.
³⁵ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
³⁶ Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. benmic@liverpool.ac.uk.
³⁷ Department of Neurology, Walton Centre of Neurosurgery and Neurology, Liverpool, UK. benmic@liverpool.ac.uk.
³⁸ Institute of Infection, Veterinary and Ecological Sciences, National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. benmic@liverpool.ac.uk.
³⁹ Encephalitis International, Malton, UK. benmic@liverpool.ac.uk.

PMID: 39870668
PMCID: PMC11772688
DOI: 10.1038/s41598-024-80833-0

Multicenter Study

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study

Rajish S K Shil et al. Sci Rep. 2025.

. 2025 Jan 27;15(1):3443.

doi: 10.1038/s41598-024-80833-0.

Authors

Collaborators

COVID-CNS Study Group:
John P Aggleton, Ali M Aggleton, Ammar Al-Chalabi, Christopher M Allen, Jay Amin, Cherie Armour, Mark R Baker, Suzanne Barret, Neil Basu, Rahul Batra, Alex Berry, Laura Benjamin, Richard A I Bethlehem, Bethan Blackledge, Sarah A Boardman, John Bradley, David P Breen, Gerome Breen, Judith Breuer, Matthew Broome, Ed Bullmore, Matthew Butler, Alan Carson, Hannah Castell, Jonathan Cavanagh, Patrick Chinnery, David Christmas, David M Christmas, Jonathan R I Coleman, Alaistair Coles, Ceryce Collie, Nadine Cossette, David Cousins, Colm Cunningham, Alastair Darby, Anthony S David, Nicholas Davies, Sylviane Defres, Katherine C Dodd, Alex Dregan, Eugene Duff, Cordelia Dunai, Ava Easton, Franklyn N Egbe, Mark A Ellul, Nikos Evangelou, Bethany Facer, Peter M Fernandes, Richard Francis, Ian Galea, Afagh Garjani, Lily George, Valentina Giunchiglia, Kiran Glen, Rebecca Gregory, Michael Griffiths, Victoria Grimbly, Alexander Grundmann, Savini Gunatilake, Shahd H M Hamid, Adam Hampshire, Marc Hardwick, Jade D Harris, Ewan Harrison, NeiL A Harrison, Paul J Harrison, Monika Hartmann, Peter J Hellyer, Claire Hetherington, Orla Hilton, Julian Hiscox, Eva Maria Hodel, Angela E Holland, Matthew Hotopf, Yun Huang, Stella Hughes, Masud Husain, Sarosh Irani, Thomas A Jackson, Thomas M Jackson, Peter Jezzard, Johan Kallberg Zvrskovec, Gursharan Kalsi, Simon Keller, Nathalie Kingston, Sandar Kyaw, E Charles Leek, Gabriella Lewis, James B Lilleker, Michael P P Lunn, Claire L MacIver, Daniel Madarshahian, Parisa Mansoori, Naomi Martin, Gavin McDonnell, Emily McGlinchey, Stephen McKeever, Ryan McIlwaine, Andrew M McIntosh, David K Menon, Benedict D Michael, Karla L Miller, Dina Monssen, Christopher M Morris, Ciaran Mulholland, Akshay Nair, Edward Needham, Virginia Newcombe, Nathalie Nicholas, Timothy R Nicholson, Ronan O'Malley, Obioma Orazulume, Marlies Ostermann, Stella-Maria Paddick, Alish Palmos, Arvind Patel, Sharon Peacock, Sophie L Pendered, Sarah L Pett, Thomas A Pollak, Angela Roberts, Henry C Rogers, Silvia Rota, Rustam Al-Shahi Salman, Merna Samuel, Brendan F Sargent, Stephen J Sawcer, Adam W Seed, Scott Semple, Pamela J Shaw, Rajish S K Shil, Adam Sieradzki, Bhagteshwar Singh, Craig J Smith, Jacqueline Smith, Stephen M Smith, Tom Solomon, Leonie Taams, Arina Tamborska, John-Paul Taylor, Kukatharmini Tharmaratnam, Rhys H Thomas, Emma Thomson, William Trender, Zain-Ul-Abideen Ahmad, Jonathan Underwood, Rachel Upthegrove, Tonny Veenith, Annalena Venneri, Angela Vincent, Daniel J van Wamelen, Guy Williams, Steven Williams, Sui Hsien Wong, Greta K Wood, Nicholas Wood, Michael S Zandi, Fernando Zelaya, Kathleen E Stirrups, Laura Cocking, Rose Eichenberger, Debbie Clapham, Hannah Stark

Affiliations

¹ Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. rajishsk@liverpool.ac.uk.
² Department of Neurology, Walton Centre of Neurosurgery and Neurology, Liverpool, UK. rajishsk@liverpool.ac.uk.
³ Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. rajishsk@liverpool.ac.uk.
⁴ Institute of Infection, Veterinary and Ecological Sciences, National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. rajishsk@liverpool.ac.uk.
⁵ Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
⁶ Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
⁷ Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
⁸ Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.
⁹ Department of Neurology, Walton Centre of Neurosurgery and Neurology, Liverpool, UK.
¹⁰ Institute of Infection, Veterinary and Ecological Sciences, National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.
¹¹ Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, M6 8HD, UK.
¹² Division of Musculoskeletal & Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, UK.
¹³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 4AF, UK.
¹⁴ South London and Maudsley NHS Foundation Trust, London, UK.
¹⁵ Curtin University, Kent Street, Bentley, Perth, WA, 6102, Australia.
¹⁶ Sheffield Institute for Translational Neuroscience, 385a Glossop Road, Sheffield, UK.
¹⁷ Department of Neurology, Joondalup Healthcare Campus, 60 Shenton Avenue, JoondalupPerth, WA, 6027, Australia.
¹⁸ Midland St John of God Hospital, 1 Clayton Street, Midland, Perth, WA, 6056, Australia.
¹⁹ Department of Neurology, Charing Cross Hospital, London, UK.
²⁰ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne, NE4 5PL, UK.
²¹ UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
²² MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
²³ Laboratory of Molecular and Cell Biology, University College London, Gower St, King's Cross, London, WC1E 6BT, UK.
²⁴ Encephalitis International, Malton, UK.
²⁵ The Pandemic Institute, The Spine, Liverpool, L7 3FA, UK.
²⁶ NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge, UK.
²⁷ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
²⁸ MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
²⁹ Geoffrey Jefferson Brain Research Centre, Clinical Sciences Building, Northern Care Alliance NHS Foundation Trust, Salford, M6 8FJ, UK.
³⁰ Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, UK.
³¹ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.
³² Translational and Clinical Research, Newcastle University, Newcastle, NE1 7RU, UK.
³³ Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle, NE2 4HH, UK.
³⁴ Department of Neurology, Royal Victoria Infirmary, Newcastle, NE1 4LP, UK.
³⁵ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
³⁶ Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. benmic@liverpool.ac.uk.
³⁷ Department of Neurology, Walton Centre of Neurosurgery and Neurology, Liverpool, UK. benmic@liverpool.ac.uk.
³⁸ Institute of Infection, Veterinary and Ecological Sciences, National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. benmic@liverpool.ac.uk.
³⁹ Encephalitis International, Malton, UK. benmic@liverpool.ac.uk.

PMID: 39870668
PMCID: PMC11772688
DOI: 10.1038/s41598-024-80833-0

Abstract

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases). Among the 651 patients, [362 (55%) cases and 289 (45%) controls], a higher proportion of cases had impairment in ADLs (199 [68.9%] vs 101 [51.8%], OR 2.06, p < 0.0002) and reported symptoms impacting employment (159 [58.2%] vs 69 [35.6%] OR 2.53, p < 0.0001). There was no significant difference in the proportion with depression or anxiety between case and control groups overall. For cases, impairment of ADLs was associated with increased risk in female sex, age > 50 years and hypertension (OR 5.43, p < 0.003, 3.11, p = 0.02, 3.66, p = 0.04). Those receiving either statins or angiotensin converting enzyme (ACE) inhibitors had a lower risk of impairment in ADLs (OR 0.09, p = 0.0006, 0.17, p = 0.03). Patients with neurological or psychiatric complications of COVID-19 had worse functional outcomes than those with respiratory COVID-19 alone in terms of ADLs and employment. Female sex, age > 50 years, and hypertension were associated with worse outcomes, and statins or ACE inhibitors with better outcomes.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

**Fig. 2**
Cases vs controls, ADL and Employment.

**Fig. 3**
Cases vs Controls, anxiety and depression.

**Fig. 4**
Cases and Controls—Risk factors for ADL impairment ROC curve.

**Fig. 5**
Cases and Controls—Risk factors for impact on employment ROC curve.

See this image and copyright information in PMC

References

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Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study

Collaborators

Affiliations

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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LinkOut - more resources

Full Text Sources

Medical

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