Brain health trajectories 3 years after hospitalization for COVID-19, pneumonia, myocardial infarction, or critical illness

C Peinkhofer; C S Grønkjær; L E Bang; J U Stæhr Jensen; T L Katzenstein; J Kjærgaard; A Lebech; C Merie; V Nersesjan; P Sivapalan; P Zarifkar; M E Benros; D Kondziella

doi:10.1016/j.jns.2025.123582

Brain health trajectories 3 years after hospitalization for COVID-19, pneumonia, myocardial infarction, or critical illness

J Neurol Sci. 2025 Jun 14:475:123582. doi: 10.1016/j.jns.2025.123582. Online ahead of print.

Authors

C Peinkhofer¹, C S Grønkjær², L E Bang³, J U Stæhr Jensen⁴, T L Katzenstein⁵, J Kjærgaard³, A Lebech⁶, C Merie⁷, V Nersesjan², P Sivapalan⁴, P Zarifkar¹, M E Benros⁸, D Kondziella⁹

Affiliations

¹ Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
² Biological and Precision Psychiatry, Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
³ Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Internal Medicine, Respiratory Medicine Section, Herlev and Gentofte Hospital, Copenhagen University Hospital, Hellerup, Denmark.
⁵ Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁷ Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁸ Biological and Precision Psychiatry, Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address: michael.eriksen.benros@regionh.dk.
⁹ Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address: daniel.kondziella@regionh.dk.

PMID: 40532316
DOI: 10.1016/j.jns.2025.123582

Abstract

Background: Long-term consequences of COVID-19 seem to persist several years after initial infection; however, it is still unknown whether these consequences differ from those occurring after hospitalization for similar diseases and if they remain stable, improve, or worsen over time.

Methods: This is a prospective cohort study assessing 36-month follow-up of individuals previously monitored up to 18 months post-hospitalization. We included COVID-19 patients; hospitalized controls admitted for pneumonia, myocardial infarction or conditions requiring intensive care admission; and healthy controls. The hospitalized groups were admitted between March 1, 2020, and June 30, 2021, at two academic hospitals in Copenhagen. All participants were examined in-person between October 2023 and July 2024.

Results: We investigated 242 participants. Eighty-four hospitalized COVID-19 patients (mean [SD] age 62 [12]; 39 females [46 %]), 80 hospitalized controls (mean age, 65 [11]; 30 females [38 %]), and 78 healthy controls (mean age, 65 [14]; 45 females [58 %]). Compared to the healthy controls, COVID-19 patients had poorer SCIP scores (estimated mean: 68.0 [95 %CI, 65.6-70.5] vs 74.4 [95 %CI, 71.6-77.2]) and non-significantly higher anxiety, depression, and neurological scores. COVID-19 patients performed comparably to hospitalized controls in all outcomes (all p > .06). Cognitive function improved over time among both COVID-19 and hospitalized controls, while mental-health improved mainly in COVID-19 patients.

Conclusion: This study shows comparable brain function impairments in COVID-19 patients and hospitalized controls 36 months post-hospitalization, with gradual improvement over time. These findings are relevant for guiding patients with long-lasting symptoms after critical illness.

Keywords: Brain health; COVID-19; Cognition; Mental health.