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. 2022 Jul 1;79(7):690-698.
doi: 10.1001/jamapsychiatry.2022.1067.

Neuropsychiatric Ramifications of Severe COVID-19 and Other Severe Acute Respiratory Infections

Ashley Kieran Clift  1   2 , Tom Alan Ranger  1 , Martina Patone  1 , Carol A C Coupland  1   3 , Robert Hatch  4 , Karen Thomas  5 , Julia Hippisley-Cox  1 , Peter Watkinson  4   6
Affiliations

Neuropsychiatric Ramifications of Severe COVID-19 and Other Severe Acute Respiratory Infections

Ashley Kieran Clift et al. JAMA Psychiatry. .

Abstract

Importance: Individuals surviving severe COVID-19 may be at increased risk of neuropsychiatric sequelae. Robust assessment of these risks may help improve clinical understanding of the post-COVID syndrome, aid clinical care during the ongoing pandemic, and inform postpandemic planning.

Objective: To quantify the risks of new-onset neuropsychiatric conditions and new neuropsychiatric medication prescriptions after discharge from a COVID-19-related hospitalization, and to compare these with risks after discharge from hospitalization for other severe acute respiratory infections (SARI) during the COVID-19 pandemic.

Design, setting, and participants: In this cohort study, adults (≥18 years of age) were identified from QResearch primary care and linked electronic health record databases, including national SARS-CoV-2 testing, hospital episode statistics, intensive care admissions data, and mortality registers in England, from January 24, 2020, to July 7, 2021.

Exposures: COVID-19-related or SARI-related hospital admission (including intensive care admission).

Main outcomes and measures: New-onset diagnoses of neuropsychiatric conditions (anxiety, dementia, psychosis, depression, bipolar disorder) or first prescription for relevant medications (antidepressants, hypnotics/anxiolytics, antipsychotics) during 12 months of follow-up from hospital discharge. Maximally adjusted hazard ratios (HR) with 95% CIs were estimated using flexible parametric survival models.

Results: In this cohort study of data from 8.38 million adults (4.18 million women, 4.20 million men; mean [SD] age 49.18 [18.45] years); 16 679 (0.02%) survived a hospital admission for SARI, and 32 525 (0.03%) survived a hospital admission for COVID-19. Compared with the remaining population, survivors of SARI and COVID-19 hospitalization had higher risks of subsequent neuropsychiatric diagnoses. For example, the HR for anxiety in survivors of SARI was 1.86 (95% CI, 1.56-2.21) and for survivors of COVID-19 infection was 2.36 (95% CI, 2.03-2.74); the HR for dementia for survivors of SARI was 2.55 (95% CI, 2.17-3.00) and for survivors of COVID-19 infection was 2.63 (95% CI, 2.21-3.14). Similar findings were observed for all medications analyzed; for example, the HR for first prescriptions of antidepressants in survivors of SARI was 2.55 (95% CI, 2.24-2.90) and for survivors of COVID-19 infection was 3.24 (95% CI, 2.91-3.61). There were no significant differences observed when directly comparing the COVID-19 group with the SARI group apart from a lower risk of antipsychotic prescriptions in the former (HR, 0.80; 95% CI, 0.69-0.92).

Conclusions and relevance: In this cohort study, the neuropsychiatric sequelae of severe COVID-19 infection were found to be similar to those for other SARI. This finding may inform postdischarge support for people surviving SARI.

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Conflict of interest statement

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 during the conduct of the study; grants from HDR UK Grants for other research studies, grants from the National Institutes for Health Research (NIHR) Grants for other research studies, and grants from MRC Grants for other research studies outside the submitted work. Dr Hatch reported receiving grants from 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 Hippisley-Cox reported receiving grants from Wellcome Trust and grants from Oxford NIHR Biomedical Research Centre during the conduct of the study; being an unpaid director of QResearch (a not-for-profit organization that is a partnership between the University of Oxford and EMIS Health, which supply the QResearch database); and being a member of Scientific Advisory Group for Emergencies on COVID-19 and chair of the NERVTAG risk stratification subgroup. Dr Watkinson reported receiving grants from Wellcome during the conduct of the study; grants from the National Institute for Health Research and grants from Sensyne Health outside the submitted work; and being Chief Medical Officer for Sensyne Health prior to this work and holding shares in the company. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. First Recorded New-Onset Neuropsychiatric Diagnosis After Hospital Discharge in the Contemporary Cohort
Numbers in parentheses following general population, SARI, and COVID-19 refer to number of events and denominator. Inclusion was determined on a per-analysis basis, and therefore, the denominator counts may vary. HR indicates hazard ratio; SARI, severe acute respiratory infections.
Figure 2.
Figure 2.. First Recorded Neuropsychiatric Prescription After Hospital Discharge in the Contemporary Cohort
Numbers in parentheses following general population, SARI, and COVID-19 refer to number of events and denominator. Inclusion was performed on a per-analysis basis, and therefore, the denominator counts may vary. HR indicates hazard ratio; SARI, severe acute respiratory infections.
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