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Preexisting Neuropsychiatric Conditions and Associated Risk of Severe COVID-19 Infection and Other Acute Respiratory Infections

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is there an association between having a diagnosis of a neuropsychiatric condition and severe outcome from COVID-19 infection, and if so, is it also observed in other severe acute respiratory infections (SARIs)?

Findings  In this longitudinal cohort study of the electronic medical records from more than 11 million people, both a preexisting diagnosis of a neuropsychiatric condition and having a prescription for a related pharmacological treatment were associated with a significantly increased risk of severe outcomes from both COVID-19 infection and other SARIs, mainly to similar extents.

Meaning  These findings suggest the importance of recognizing the association of several neuropsychiatric illnesses with risk of developing a broad range of respiratory infections, not just COVID-19 infection.


Importance  Evidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs).

Objective  To determine whether preexisting diagnosis of and/or treatment for a neuropsychiatric condition is associated with severe outcomes from COVID-19 infection and other SARIs and whether any observed association is similar between the 2 outcomes.

Design, Setting, and Participants  Prepandemic (2015-2020) and contemporary (2020-2021) longitudinal cohorts were derived from the QResearch database of English primary care records. Adjusted hazard ratios (HRs) with 99% CIs were estimated in April 2022 using flexible parametric survival models clustered by primary care clinic. This study included a population-based sample, including all adults in the database who had been registered with a primary care clinic for at least 1 year. Analysis of routinely collected primary care electronic medical records was performed.

Exposures  Diagnosis of and/or medication for anxiety, mood, or psychotic disorders and diagnosis of dementia, depression, schizophrenia, or bipolar disorder.

Main Outcomes and Measures  COVID-19–related mortality, or hospital or intensive care unit admission; SARI-related mortality, or hospital or intensive care unit admission.

Results  The prepandemic cohort comprised 11 134 789 adults (223 569 SARI cases [2.0%]) with a median (IQR) age of 42 (29-58) years, of which 5 644 525 (50.7%) were female. The contemporary cohort comprised 8 388 956 adults (58 203 severe COVID-19 cases [0.7%]) with a median (IQR) age of 48 (34-63) years, of which 4 207 192 were male (50.2%). Diagnosis and/or treatment for neuropsychiatric conditions other than dementia was associated with an increased likelihood of a severe outcome from SARI (anxiety diagnosis: HR, 1.16; 99% CI, 1.13-1.18; psychotic disorder diagnosis and treatment: HR, 2.56; 99% CI, 2.40-2.72) and COVID-19 (anxiety diagnosis: HR, 1.16; 99% CI, 1.12-1.20; psychotic disorder treatment: HR, 2.37; 99% CI, 2.20-2.55). The effect estimate for severe outcome with dementia was higher for those with COVID-19 than SARI (HR, 2.85; 99% CI, 2.71-3.00 vs HR, 2.13; 99% CI, 2.07-2.19).

Conclusions and Relevance  In this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.

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Article Information

Accepted for Publication: September 14, 2022.

Published Online: November 9, 2022. doi:10.1001/jamapsychiatry.2022.3614

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Ranger TA et al. JAMA Psychiatry.

Corresponding Author: Peter Watkinson, MD, Critical Care Research Group, Kadoorie Centre Level 3, John Radcliffe Hospital, Oxford, England OX3 9DU (peter.watkinson@ndcn.ox.ac.uk).

Author Contributions: Drs Ranger and Clift had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Ranger and Clift are considered co–first authors. Drs Watkinson and Hippisley-Cox are considered co–senior authors.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Ranger, Clift, Patone, Coupland, Watkinson, Hippisley-Cox.

Drafting of the manuscript: Ranger, Clift, Hatch, Watkinson.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Ranger, Clift, Patone, Coupland.

Obtained funding: Watkinson, Hippisley-Cox.

Administrative, technical, or material support: Ranger, Clift, Hatch, Hippisley-Cox.

Supervision: Coupland, Watkinson, Hippisley-Cox.

Conflict of Interest Disclosures: Dr Clift reported receiving grants from Cancer Research UK during the conduct of the study. Dr Coupland reported receiving grants from Wellcome Trust, John Fell Oxford University Press Research Fund, Oxford Wellcome Institutional Strategic Support Fund, and Cancer Research UK during the conduct of the study. Dr Hatch reported receiving grants from Wellcome Trust and the National Institute for Health and Care Research (NIHR) doctoral research fellowship during the conduct of the study. Ms Thomas reported receiving grants from Wellcome Trust during the conduct of the study. Dr Watkinson reported receiving grants from Wellcome Trust, NIHR, and Sensyne Health; personal fees from Sensyne Health; being a chief medical officer for Sensyne Health; and holding shares in Sensyne Health outside the submitted work. Dr Hippisley-Cox reported receiving grants from Wellcome Trust, Medical Research Council, and the John Fell Fund; nonfinancial support from QResearch as director of QResearch; being a founder, shareholder, and previous director of ClinRisk Ltd, a software company; and being a current work member of Scientific Advisory Group for Emergencies committee for the UK government. No other disclosures were reported.

Funding/Support: This study was supported by grant 221514/Z/20/Z from the Wellcome Trust, the John Fell Oxford University Press Research Fund, grant 204826/Z/16/Z from the Oxford Wellcome Institutional Strategic Support Fund, and grants C5255/A18085 and C2195/A31310 (Dr Clift) from Cancer Research UK, through the Cancer Research UK Oxford Centre.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: NHS Digital: the Hospital Episode Statistics data used in this analysis are copyright 2021, the Health and Social Care Information Centre, and reused with the permission of the Health and Social Care Information Centre (and the University of Oxford). All rights reserved. NHS Digital bear(s) no responsibility for the analysis or interpretation of the data. Public Health England: the COVID-19 test data is collated, maintained, and quality assured by Public Health England. Access to the data was facilitated by the Public Health England Office for Data Release. Public Health England bear(s) no responsibility for the analysis or interpretation of the data. Intensive Care National Audit & Research Centre (ICNARC): this publication is based on data derived from the ICNARC Case Mix Programme Database. The Case Mix Programme is the national, comparative audit of patient outcomes from adult critical care coordinated by the ICNARC. For more information on the representativeness and quality of these data, please contact ICNARC. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of ICNARC. Office of National Statistics (ONS): the ONS bear(s) no responsibility for the analysis or interpretation of the data.

Additional Contributions: We thank the EMIS practices who contributed to the QResearch; EMIS Health and the Chancellor masters and scholars of the University of Oxford for expertise in establishing, developing, and supporting the QResearch database; all the staff in the critical care units participating in the Case Mix Programme; and the Office for National Statistics for providing the mortality data. No one was financially compensated for their contribution.

Additional Information: To guarantee the confidentiality of personal and health information, only the authors have had access to the data during the study in accordance with the relevant license agreements. Access to the QResearch data is according to the information on the QResearch website (http://www.qresearch.org). Information regarding access to the QResearch database, including how to submit a project application, who is eligible, and costs, is available at: https://www.qresearch.org/information/information-for-researchers/.

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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