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Psychiatric disorder risk may increase after severe COVID and acute respiratory infections – Oxford study

A UK study had found that the more than 32,000 survivors of severe COVID-19 and more than 16,000 survivors of other severe respiratory infections were at significantly higher risk than the general population for new anxiety disorders, dementia, psychosis, bipolar disorder and new neuropsychiatric drug prescriptions in the first year after hospital release.

In the observational study, a team led by University of Oxford researchers analysed data from all 8,38m adults registered in national databases from 24 January 2020 to 7 July 2021.

Risk of new psychiatric prescriptions

Relative to the general population, the 32,525 survivors of COVID-19 and 16,679 survivors of other severe acute respiratory infections (SARI) were at higher risk for subsequent diagnosis of neuropsychiatric illnesses, the investigators found, but they noted that the absolute risks were low.

The hazard ratio (HR) for anxiety in SARI survivors was 1.86 (95% confidence interval [CI], 1.56 to 2.21) and 2.36 (95% CI, 2.03 to 2.74) for COVID-19 survivors.

The HR for dementia was 2.55 (95% CI, 2.17 to 3.00) for SARI survivors and 2.63 (95% CI, 2.21 to 3.14) for those diagnosed as having COVID-19.

In an analysis limited to SARI survivors as the reference group and COVID-19 as the comparator group, there were no significant differences in rates of newly-diagnosed anxiety disorder (adjusted HR, 1.00; 95% CI, 0.79 to 1.27), dementia (HR, 0.88; 95% CI, 0.69 to 1.13), depression (HR, 0.63; 95% CI, 0.25 to 1.58), or bipolar disorder (HR, 0.74; 95% CI, 0.32 to 1.69).

Nor did the two groups differ in their post-hospitalisation risk of new prescriptions for anti-depressants (adjusted HR, 1.07; 95% CI, 0.90 to 1.27) or hypnotic or anti-anxiety medication (HR, 0.95; 95% CI, 0.80 to 1.24). But COVID-19 survivors had a 20% lower risk of a first anti-psychotic prescription than SARI survivors did (HR, 0.80; 95% CI, 0.69 to 0.92).

Findings for all neuropsychiatric medications analysed were similar. The adjusted HR for new prescriptions of anti-depressants for SARI survivors was 2.55 (95% CI, 2.24 to 2.90), compared with 3.24 (95% CI, 2.91 to 3.61) for COVID-19 survivors.

The HR for new hypnotic or anti-anxiety drug prescriptions was 3.10 (95% CI, 2.74 to 3.51) for SARI survivors and 3.79 (95% CI, 3.38 to 4.25) for COVID-19 survivors, while the HR for new anti-psychotic drug prescriptions was 4.64 (95% CI, 4.20 to 5.12) for SARI survivors and 4.78 (95% CI, 4.28 to 5.33) for those with COVID-19. Direct comparison of the COVID-19 and SARI groups revealed no significant differences other than a lower risk for anti-psychotic prescriptions in the former (HR, 0.80; 95% CI, 0.69 to 0.92).

Role of disease severity

Although the relative risks of these outcomes in survivors of severe COVID-19 and SARI hospitalisation was significantly higher than for the general population, the absolute risks were low, the study authors noted.

“Although post–COVID-19 syndrome is of legitimate topical interest in the current context of uncertainty regarding optimal support for survivors of COVID-19, our results suggest that from the perspective of formally diagnosed or treated neuropsychiatric complications, severe COVID-19 does not predicate markedly different morbidity rates than other forms of SARI,” the researchers wrote.

The elevated risks of neuropsychiatric conditions among both SARI and COVID-19 survivors could result from physiologic alterations, physical deconditioning and other infection-related stressors, they said.

Ultimately, they said, the findings suggest that disease severity, not the causative pathogen, has a role in neuropsychiatric disorders after severe respiratory infections. “These results may help refine our understanding of the post-severe COVID-19 phenotype and may inform post-discharge support for patients requiring hospital-based and intensive care for SARI regardless of causative pathogen,” they concluded.

Study details

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

Ashley Kieran Clift, Tom Alan Ranger, Martina Patone, et al

Published in JAMA Psychiatry on 22 May 2022

Key Points
Question What are the risks of neuropsychiatric disorders in adults surviving COVID-19 hospitalisation, and how do these compare with non-COVID severe respiratory infections?
Findings In this cohort study of data from more than 8m adults in England, during the COVID-19 pandemic, risks of new anxiety disorder, dementia, psychotic disorder and bipolar disorder diagnoses were significantly increased in adults surviving hospitalisation for COVID-19 or other severe acute respiratory infections compared with the general population. Risks of neuropsychiatric illnesses or commencement of related medications were similar for COVID-19 and non-COVID severe respiratory infections.
Meaning The results of this study suggest that disease severity, rather than pathogen, is a relevant factor associated with neuropsychiatric ramifications after severe respiratory infections.


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 post-pandemic planning.
Objective To quantify the risks of new-onset neuropsychiatric conditions and new neuropsychiatric medication prescriptions after discharge from a COVID-19–related hospitalisation, 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 24 January 2020 to 7 July 2021.
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.

In this cohort study of data from 8.38m adults (4.18m women, 4.20m 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 hospitalisation 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 analysed; 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.


CIDRAP article – Severe COVID, similar illnesses may raise risk for psychiatric disorders (Open access)


JAMA Psychiatry article – Neuropsychiatric Ramifications of Severe COVID-19 and Other Severe Acute Respiratory Infections (Open access)


See more from MedicalBrief archives:


Neuropsychiatric manifestations of COVID-19 in SA – Wits


One in eight COVID-19 patients receive psychiatric diagnosis within 6 months — UK analysis


Brain complications in patients with COVID-19 — First UK nationwide surveillance study



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