Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non-COVID-19 Illness

Importance: Prolonged neuropsychiatric and cognitive symptoms are increasingly reported in patients after COVID-19, but studies with well-matched controls are lacking.

Objective: To investigate cognitive impairment, neuropsychiatric diagnoses, and symptoms in survivors of COVID-19 compared with patients hospitalized for non-COVID-19 illness.

Design, Setting, and Participants: This prospective case-control study from a tertiary referral hospital in Copenhagen, Denmark, conducted between July 2020 and July 2021, followed up hospitalized COVID-19 survivors and control patients hospitalized for non-COVID-19 illness, matched for age, sex, and intensive care unit (ICU) status 6 months after symptom onset.

Exposures: Hospitalization for COVID-19.

Main Outcomes and Measures: Participants were investigated with the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semi-structured interview for subjective symptoms. Primary outcomes were total MoCA score and new onset of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses, subjective symptoms, and neurologic examination results. All outcomes were adjusted for age, sex, ICU admission, admission length, and days of follow-up. Secondary outcomes were adjusted for multiple testing.

Results: A total of 85 COVID-19 survivors (36 [42%] women; mean [SD] age 56.8 [14] years) after hospitalization and 61 matched control patients with non-COVID-19 illness (27 [44%] women, mean age 59.4 years [SD, 13]) were enrolled. Cognitive status measured by total geometric mean MoCA scores at 6-month follow-up was lower (P = .01) among COVID-19 survivors (26.7; 95% CI, 26.2-27.1) than control patients (27.5; 95% CI, 27.0-27.9). The cognitive status improved substantially (P = .004), from 19.2 (95% CI, 15.2-23.2) at discharge to 26.1 (95% CI, 23.1-29.1) for 15 patients with COVID-19 with MoCA evaluations from hospital discharge. A total of 16 of 85 patients with COVID-19 (19%) and 12 of 61 control patients (20%) had a new-onset psychiatric diagnosis at 6-month follow-up, which was not significantly different (odds ratio, 0.93; 95% CI, 0.39-2.27; P = .87). In fully adjusted models, secondary outcomes were not significantly different, except anosmia, which was more common after COVID-19 (odds ratio, 4.56; 95% CI, 1.52-17.42; P = .006); but no longer when adjusting for multiple testing.

Conclusions and Relevance: In this prospective case-control study, cognitive status at 6 months was worse among survivors of COVID-19, but the overall burden of neuropsychiatric and neurologic signs and symptoms among survivors of COVID-19 requiring hospitalization was comparable with the burden observed among matched survivors hospitalized for non-COVID-19 causes.