Vardan Nersesjan1,2,3, Lise Fonsmark4, Rune H B Christensen1, Moshgan Amiri3, Charlotte Merie4, Anne-Mette Lebech5,6, Terese Katzenstein5, Lia E Bang7, Jesper Kjærgaard7, Daniel Kondziella3,6, Michael E Benros1,2. 1. Biological and Precision Psychiatry, Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. 2. Faculty of Health and Medical Sciences, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. 3. Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4. Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 7. Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Abstract
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.
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.
Authors: Vardan Nersesjan; Moshgan Amiri; Anne-Mette Lebech; Casper Roed; Helene Mens; Lene Russell; Lise Fonsmark; Marianne Berntsen; Sigurdur Thor Sigurdsson; Jonathan Carlsen; Annika Reynberg Langkilde; Pernille Martens; Eva Løbner Lund; Klaus Hansen; Bo Jespersen; Marie Norsker Folke; Per Meden; Anne-Mette Hejl; Christian Wamberg; Michael E Benros; Daniel Kondziella Journal: J Neurol Date: 2021-01-13 Impact factor: 4.849
Authors: Dominic L Sykes; Luke Holdsworth; Nadia Jawad; Pumali Gunasekera; Alyn H Morice; Michael G Crooks Journal: Lung Date: 2021-02-11 Impact factor: 3.777
Authors: K W Miskowiak; S Johnsen; S M Sattler; S Nielsen; K Kunalan; J Rungby; T Lapperre; C M Porsberg Journal: Eur Neuropsychopharmacol Date: 2021-03-29 Impact factor: 4.600
Authors: Hannah E Davis; Gina S Assaf; Lisa McCorkell; Hannah Wei; Ryan J Low; Yochai Re'em; Signe Redfield; Jared P Austin; Athena Akrami Journal: EClinicalMedicine Date: 2021-07-15
Authors: Bruno Biagianti; Asia Di Liberto; Aiello Nicolò Edoardo; Ilaria Lisi; Letizia Nobilia; Giulia Delor de Ferrabonc; Elisa R Zanier; Nino Stocchetti; Paolo Brambilla Journal: Front Aging Neurosci Date: 2022-07-01 Impact factor: 5.702