Neuropsychiatric ramifications of severe COVID-19 and other severe acute respiratory infections

Importance: Individuals surviving severe COVID-19 may be at increased risk of neuropsychiatric sequelae. Robust assessment of these risks may 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 following discharge from a COVID-19-related hospitalization. To compare these to risks after discharge from hospitalization for other severe acute respiratory infections (SARI) during the COVID-19 pandemic. Design: Cohort study from 24th January 2020 to 7th July 2021. Setting: 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. Participants: Adults aged 18+ years. Exposures: COVID-19 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, hypnotic/anxiolytics, antipsychotics) during 12 months follow-up from hospital discharge. Maximally-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using flexible parametric survival models. Results: The cohort comprised 8.38 million adults (4.18 million women, 4.20 million men; mean age 49.18 years): 16,679 survived a hospital admission for SARI, and 32,525 survived a hospital admission for COVID-19. Compared to the remaining population, SARI and COVID-19 hospitalization survivors had higher risks of all subsequent neuropsychiatric diagnoses, e.g.: anxiety (HR 1.86 [95% CI: 1.56-2.21] and 2.36 [2.03-2.74], respectively); dementia (2.55 [2.17-3.00] and 2.63 [2.21-3.14]). Similar trends were observed for all medications analysed, e.g., first prescriptions of anti-depressants (HR 2.55 [95% CI: 2.24-2.90], 3.24 [2.91-3.61], respectively). There were no significant differences observed when directly comparing the COVID-19 group to the SARI group apart from a lower risk of anti-psychotic prescriptions in the former (HR 0.80, 95% CI 0.69-0.92). Conclusions and relevance: The neuropsychiatric sequelae of severe COVID-19 are similar to those for other severe acute respiratory infections. This may inform post-discharge support for people surviving severe respiratory acute infections.